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for invention","granted":true,"earliest_filing_date":"2008-08-28","grant_date":"2014-12-23","anticipated_term_date":"2030-05-04","has_disclaimer":false,"patent_status":"ACTIVE","publication_count":2,"has_spc":false,"has_grant_event":true,"has_entry_into_national_phase":false},"abstract":{"en":[{"text":"The present invention relates to compounds of general formula I wherein n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are defined as stated hereinafter, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases, which have valuable properties, the preparation thereof, the pharmaceutical compositions containing the pharmacologically effective compounds, the preparation thereof and the use thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"}]},"abstract_lang":["en"],"has_abstract":true,"claim":{"en":[{"text":"1. A compound of the formula I wherein R 1 denotes (a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 , (b) a C 1-3 -alkyl group wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, (c) a C 3-6 -cycloalkyl group optionally substituted by a group R 1.2 , (d) a C 2-6 -alkenyl group, (e) a C 2-6 -alkynyl group, (f) an aryl-C 1-2 -alkylene group optionally substituted by 1, 2 or 3 groups R 1.3 , (g) a five-membered heteroaryl group optionally substituted by by 1, 2 or 3 groups R 1.4 , which contains at least one N, O or S atom and optionally also contains one, two or three further N atoms and may additionally be benzo-fused, (h) a six-membered heteroaryl group optionally substituted by a group R 1.4 , which contains one, two or three N atoms and may additionally be benzo-fused, (i) —O—R 1.1.1 or (j) —NR 1.1.2 R 1.1.4 , R 1.1 denotes halogen, —NO 2 , —CN, C 3-6 -cycloalkyl, —OR 1.1.1 , —SR 1.1.1 , —C(O)R 1.1.1 , —S(O) 2 —R 1.1.2 , —O—S(O) 2 —R 1.1.1 , —CO 2 R 1.1.1 , —O—C(O)—R 1.1.1 , —NR 1.1.3 R 1.1.4 , —NR 1.1.3- C(O)—R 1.1.1 , —NR 1.1.3- C(O)—R 1.1.1 , —NR 1.1.3- CO 2 —R 1.1.1 , —C(O)—NR 1.1.3 R 1.1.4 , R 1.1.1 denotes (a) H, (b) C 1-4 -alkyl, (c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, (d) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.1.1.1 , (e) C 3-6 -cycloalkyl, (f) a pyridyl group optionally substituted by 1, 2 or 3 groups R 1.1.1.2 , R 1.1.1.1 independently of one another denote (b) halogen, —NO 2 , —CN, —OH, —O—C 1-4 -alkyl, C 3-6 -cycloalkyl, C 1-4 -alkyl, (c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, R 1.1.1.2 independently of one another denote halogen or C 1-4 -alkyl, R 1.1.2 denotes (a) C 1-4 -alkyl, (b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, (c) —O—C 1-4 -alkyl, (d) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.1.1.1 , R 1.1.3 , R 1.1.4 independently of one another denote (a) H, (b) a C 1-4 -alkyl group optionally substituted by 1, 2 or 3 groups R 1.1.4.1 , (c) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.1.1.1 , (d) C 3-6 -cycloalkyl, or R 1.1.3 and R 1.1.4 together with the N atom to which they are bound form a 4-, 5- or 6-membered heterocyclic ring, which may additionally contain a further heteroatom selected from N, O and S, or R 1.1.3 and R 1.1.4 together with the N atom to which they are bound form a cyclic imide, R 1.1.4.1 independently of one another denote halogen, —NH 2 , —NH(C 1-4 -alkyl), —N(C 1-4 -alkyl) 2 or —SO 2 —R 1.1.2 , R 1.2 denotes halogen, —NO 2 , —CN or phenyl, R 1.3 denotes (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —CO 2 R 1.1.1 , C 1-6 -alkyl, (b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, R 1.4 independently of one another denote (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —S(O)—R 1.1.2 , —NR 1.1.3 R 1.1.4 , C 1-6 -alkyl, (b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or (c) an oxo group, R 2 denotes (a) H, C 1-4 -alkyl or (b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, R 3 independently of one another denote (a) H, halogen, —CN, —OH, C 1-6 -alkyl, C 3-7 -cycloalkyl, —O—C 1-4 -alkyl, —O—CF 3 , —O—C 3-6 -cycloalkyl, —N(C 1-3 -alkyl) 2 , —C(O)—NH 2 , —(SO 2 )NH 2 , —SO 2 —C 1-3 -alkyl, (b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, R 4 , R 5 , R 6 , R 7 , R 8 independently of one another denote (a) H, halogen, —CN, —OH, (b) C 1-6 -alkyl, wherein two adjacent substituents together may denote a trimethylene or tetramethylene group, (c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, (d) C 3-7 -cycloalkyl, (e) —O—C 1-6 -alkyl, wherein two adjacent substituents may denote a methylenedioxy or ethylenedioxy group, (f) —O—CF 3 , —O—C 3-7 -cycloalkyl, (g) —NH 2 , —NH(C 1-3 -alkyl), —N(C 1-3 -alkyl) 2 , (h) —C(O)—R 8.1 , (i) —SO 2 —R 8.2 , (j) a five-membered heteroaryl group optionally substituted by one or two C 1-3 -alkyl groups which is selected from among pyrrolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, imidazolyl, pyrazolyl, triazolyl and tetrazolyl, (k) a six-membered heteroaryl group optionally substituted by one or two C 1-3 -alkyl groups which is selected from among pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl and triazinyl, R 8.1 denotes —NH 2 , —NH(C 1-6 -alkyl),—N(C 1-6 -alkyl) 2 , N-acetidinyl, N-pyrrolidinyl, N-piperidinyl, N-morpholinyl, —OH, —O—C 1-8 -alkyl, —O—C 3-7 -cycloalkyl, R 8.2 denotes —NH 2 , —NH(C 1-6 -alkyl),—N(C 1-6 -alkyl) 2 , N-acetidinyl, N-pyrrolidinyl, N-piperidinyl, N-morpholinyl and n denotes one of the numbers 0, 1, 2, 3 or 4, or a salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"2. A compound of the formula I according to claim 1 , wherein R 1 denotes (a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 , (b) a C 1-3 -alkyl group wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, (c) a C 3-6 -cycloalkyl group optionally substituted by a group R 1.2 , (e) a five-membered heteroaryl group optionally substituted by a group R 1.4 , which contains at least one N, O or S atom and which optionally additionally contains one, two or three further N atoms, or (f) a six-membered heteroaryl group optionally substituted by a group R 1.4 , which contains one, two or three N atoms, R 1.1 denotes C 3-6 -cycloalkyl, —OR 1.1.1 , —NR 1.1.3 R 1.1.4 , —C(O)—NR 1.1.3 R 1.1.4 , —CN, —CO 2 R 1.1.1 , —S(O) 2 —C 1-6 -alkyl or —O—S(O) 2 —C 1-6 -alkyl, R 1.1.1 denotes (a) H, (b) C 1-4 -alkyl, (c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or (d) C 3-6 -cycloalkyl, R 1.1.3 , R 1.1.4 independently of one another denote (a) H, (b) C 1-4 -alkyl or (c) C 3-6 -cycloalkyl, and R 1.2 denotes halogen, —NO 2 , —CN or phenyl, R 1.3 denotes (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —CO 2 R 1.1.1 , C 1-6 -alkyl or (b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, and R 1.4 denotes (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —NR 1.1.3 R 1.1.4 , C 1-6 -alkyl, (b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or (c) an oxo group, or a salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"3. A compound of the formula I according to claim 1 , wherein R 1 denotes (a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 , (b) a C 1-3 -alkyl group wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, (c) a C 3-6 -cycloalkyl group optionally substituted by a group R 1.2 , (e) a five-membered heteroaryl group optionally substituted by a group R 1.4 , which contains at least one N, O or S atom and which optionally additionally contains one, two or three further N atoms, or (f) a six-membered heteroaryl group optionally substituted by a group R 1.4 , which contains one, two or three N atoms, R 1.1 denotes C 3-6 -cycloalkyl, —OR 1.1.1 , —NR —C(O)—NR —CN, —CO 2 R 1.1.1 , —S(O) 2 —C 1-6 -alkyl or —O—S(O) 2 —C 1-6 -alkyl, R 1.1.1 denotes (a) H, (b) C 1-4 -alkyl, (c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or (d) C 3-6 -cycloalkyl, R 1.1.3 , R 1.1.4 independently of one another denote (a) H, (b) C 1-4 -alkyl or (c) C 3-6 -cycloalkyl, R 1.2 denotes halogen, —NO 2 , —CN or phenyl, R 1.3 denotes (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —CO 2 R 1.1.1 , C 1-6 -alkyl or (b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, R 1.4 denotes (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —NR 1.1.3 R 1.1.4 , C 1-6 -alkyl, (b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or (c) an oxo group R 2 denotes H or C 1-3 -alkyl, R 3 independently of one another denote (a) H, halogen, C 1-3 -alkyl, —O—C 1-3 -alkyl or (b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, R 4 denotes H or halogen, R 5 denotes (a) H, halogen, (b) C 1-3 -alkyl, (c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, (d) —O—C 1-3 -alkyl, (e) —C(O)—O—C 1-3 -alkyl or —C(O)—NH 2 , R 6 denotes (a) H, halogen, (b) C 1-3 -alkylene-R 6.1 , (c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, (d) —OH, —O—C 1-4 -alkyl, (e) —O—CHF 2 , —O—CF 3 , (f) —C(O)—O—R 6.2 , —CN, —C(O)—CH 3 , —C(O)—NH 2 or (g) pyrrolyl, R 6.1 denotes H, —OH, R 6.2 denotes H, C 1-3 -alkyl, R 7 denotes (a) H, halogen, (b) C 1-3 -alkyl, (c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, (d) —O—C 1-3 -alkyl, (e) —C(O)—NH 2 or —C(O)-pyrrolidinyl, and R 8 denotes (a) H, halogen, (b) C 1-4 -alkyl, (c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, (d) —O—C 1-3 -alkyl, (e) —O—CF 3 , (f) —CN, —C(O)—NH 2 or (g) pyrrolyl, or a salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"4. A compound of the formula formula I according to claim 1 , wherein R 1 denotes (a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 , (b) a C 1-3 -alkyl group wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, (d) a five-membered heteroaryl group optionally substituted by a group R 1.4 , which is selected from among furanyl, isoxazolyl, isothiazolyl, oxazolyl, thiazolyl, pyrazolyl, thiadiazolyl, oxadiazolyl, triazolyl, tetrazolyl, imidazolyl, indolyl, thienyl, pyrrolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl and benzisoxazinyl, or (e) a six-membered heteroaryl group optionally substituted by a group R 1.4 , which is selected from among pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, quinazolinyl and quinoxazinyl, R 1.1 denotes C 3-6 -cycloalkyl, —OR —NR 1.1.3 R 1.1.4 , —C(O)—NR 1.1.3 R 1.1.4 , —CN, —CO 2 R 1.1.1 , —S(O) 2 -C 1-6 -alkyl or —O—S(O) 2 —C 1-6 -alkyl, R 1.1.1 denotes (a) H, (b) C 1-4 -alkyl, (c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or (d) C 3-6 -cycloalkyl, R 1.1.3 , R 1.1.4 independently of one another denote (a) H, (b) C 1-4 -alkyl or (c) C 3-6 -cycloalkyl, R 1.3 denotes (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —CO 2 R 1.1.1 , C 1-6 -alkyl or (b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, and R 1.4 denotes (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , C 1-6 -alkyl, (b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or (c) an oxo group, or a salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"5. A compound of the formula I according to claim 1 , wherein R 1 denotes or a salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"6. A compound of the formula I according to claim 1 , wherein R 2 denotes H or C 1-3 -alkyl, or a salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"7. A compound of the formula I according to claim 1 , wherein R 3 independently of one another denote (a) H, halogen, C 1-3 -alkyl, —O—C 1-3 -alkyl or (b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or a salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"8. A compound of the formula I according to claim 1 , wherein R 4 denotes H or halogen, or a salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"9. A compound of the formula I according to claim 1 , wherein R 5 denotes (a) H, halogen, (b) C 1-3 -alkyl, (c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, (d) —O—C 1-3 -alkyl, (e) —C(O)—O—C 1-3 -alkyl or —C(O)—NH 2 , or a salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"10. A compound of the formula I according to claim 1 , wherein R 6 denotes (a) H, halogen, (b) C 1-3 -alkylene—R 6.1 , (c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, (d) —OH, —O—C 14 -alkyl, (e) —OCHF 2 , —O—CF 3 , (f) —C(O)—O—R 6.2 , —CN, —C(O)—CH 3 , —C(O)—NH 2 or (g) pyrrolyl, R 6.1 denotes H or —OH and R 6.2 denotes H or C 1-3 -alkyl, or a salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"11. A compound of the formula I according to claim 1 , wherein R 7 denotes (a) H, halogen, (b) C 1-3 -alkyl, (c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, (d) —O—C 1-3 -alkyl, (e) —C(O)—NH 2 or —C(O)-pyrrolidinyl, or a salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"12. A compound of the formula I according to claim 1 , wherein R 8 denotes (a) H, halogen, (b) C 14 -alkyl, (c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, (d) —O—C 1-3 -alkyl, (e) —O—CF 3 , (f) —CN, —C(O)—NH 2 or (g) pyrrolyl, or a salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"13. A compound of the formula I according to claim 1 , wherein R 1 denotes R 2 denotes H or —CH 3 , R 3 denotes H, F, —CF 3 , —CH 3 or —O—CH 3 , R 4 denotes H or Cl, R 5 denotes H, Cl, C 1-3 -alkyl, —CF 3 , —O—C 1-3 -alkyl, —C(O)—O—C 1-3 -alkyl or —C(O)—NH 2 , R 6 denotes H, F, Cl, C 1-3 -alkyl, —CF 3 , —O—C 1-4 -alkyl, —OCF 3 , —C(O)—NH 2 or pyrrolyl, R 7 denotes H, F, Cl, C 1-3 -alkyl, —CF 3 , —O—C 1-3 -alkyl, —C(O)—NH 2 or —C(O)-pyrrolidinyl, and R 8 denotes H, F, Cl, Br, C 1-4 -alkyl, —CF 3 , —O—C 1-3 -alkyl, —OCF 3 , —C(O)—NH 2 , —OCF 3 or pyrrolyl, or a salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"14. A compound of the formula I according to claim 1 , wherein R 1 denotes R 2 denotes H, —CH 3 or —C 2 H 5 , R 3 denotes H, F, Cl, —CF 3 , —CH 3 or —O—CH 3 , R 4 denotes H or Cl, R 5 denotes H, Cl, C 1-3 -alkyl, —CF 3 , —O—C 1-3 -alkyl, —C(O)—O—C 1-3 -alkyl or —C(O)—NH 2 , R 6 denotes H, F, Cl, Br, —CN, C 1-3 -alkyl, —CF 3 , —COOH, —COO—C 1-3 -alkyl, —CH(OH)CH 3 , —OH, —O—C 1-4 -alkyl, —OCF 3 , —OCHF 2 , —C(O)—CH 3 , —C(O)—NH 2 or pyrrolyl, R 7 denotes H, F, Cl, C 1-3 -alkyl, —CF 3 , —O—C 1-3 -alkyl, —C(O)—NH 2 or —C(O)-pyrrolidinyl and R 8 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, —CF 3 , —O—C 1-3 -alkyl, —OCF 3 , —C(O)—NH 2 , —OCF 3 or pyrrolyl, or a salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"15. A compound of the formula I according to claim 1 , selected from the group consisting of: No.Structure(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108)(109)(110)(111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121)(122)(123)(124)(125)(126)(127)(128)(129)(130)(131)(132)(133)(134)(135)(136)(137)(138)(139)(140)(141)(142)(143)(144)(145)(146)(147)(148)(149)(150)(151)(152)(153)(154)(155)(156)(157)(158)(159)(160)(161)(162)(163) or a salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"16. A physiologically acceptable salt of a compound as in any one of claims 1 - 15 .","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"17. A pharmaceutical composition comprising a compound as in any one of claims 1 - 15 , or a physiologically acceptable salt thereof together with an inert carrier or diluents.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"},{"text":"18. A method for treating acute pain, visceral pain, neuropathic pain, inflammatory/pain receptor-mediated pain, tumour pain and headache diseases, which method comprises administering to a host suffering from the same a therapeutically effective amount of a compound as in any one of claims 1 - 15 , or a physiologically acceptable salt thereof.","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"}]},"claim_lang":["en"],"has_claim":true,"description":{"en":{"text":"The present invention relates to compounds of general formula I wherein n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are defined as stated hereinafter, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases, which have valuable properties, the preparation thereof, the pharmaceutical compositions containing the pharmacologically effective compounds, the preparation thereof and the use thereof. DETAILED DESCRIPTION OF THE INVENTION In the above general formula I in a first embodiment R 1 denotes (a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 ,(b) a C 1-3 -alkyl group wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(c) a C 3-6 -cycloalkyl group optionally substituted by a group R 1.2 ,(d) a C 2-6 -alkenyl group,(e) a C 2-6 -alkynyl group,(f) an aryl-C 0-2 -alkylene group optionally substituted by 1, 2 or 3 groups R 1.3 ,(g) a five-membered heteroaryl group optionally substituted by 1, 2 or 3 groups R 1.4 , which contains at least one N, O or S atom and optionally also contains one, two or three further N atoms and may additionally be benzo-fused,(h) a six-membered heteroaryl group optionally substituted by a group R 1.4 , which contains one, two or three N atoms and may additionally be benzo-fused,(i) —O—R 1:1.1 or(j) —NR 1.1.3 R 1.1.4 ,R 1.1 denotes halogen, —NO 2 , —CN, C 3-6 -cycloalkyl, —OR 1.1.1 , —SR 1.1.1 , —C(O)R 1.1.1 , —S(O) 2 —R 1.1.2 , —O—S(O) 2 —R 1.1.1 , —CO 2 R 1.1.1 , —O—C(O)—R 1.1.1 , —NR 1.1.3 R 1.1.4 , —NR 1.1.3- C(O)—R 1.1.1 , —NR 1.1,3 -C(O)—R 1.1.1 , —NR 1.1,3- CO 2 —R 1.1.1 , —C(O)—NR 1.1.3 R 1.1.4 ,R 1.1.1 denotes (a) H,(b) C 1-4 -alkyl,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(d) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.1.1.1 ,(e) C 3-6 -cycloalkyl,(f) a pyridyl group optionally substituted by 1, 2 or 3 groups R 1.1.1.2 ,R 1.1.1.1 independently of one another denote (b) halogen, —NO 2 , —CN, —OH, —O—C 1-4 -alkyl, C 3-6 -cycloalkyl, C 1-4 -alkyl,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,R 1.1.1.2 independently of one another denote halogen or C 1-4 -alkyl,R 1.1.2 denotes (a) C 1-4 -alkyl,(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(c) —O—C 1-4 -alkyl,(d) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.1.1.1 ,R 1.1.3 ,R 1.1.4 independently of one another denote (a) H,(b) a C 1-4 -alkyl group optionally substituted by 1, 2 or 3 groups R 1.1.4.1 ,(c) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.1.1.1 ,(d) C 3-6 -cycloalkyl, orR 1.1.3 and R 1.1.4 together with the N atom to which they are bound form a 4-, 5- or 6-membered heterocyclic ring, which may additionally contain a further heteroatom selected from N, O and S, orR 1.1.3 and R 1.1.4 together with the N atom to which they are bound form a cyclic imide,R 1.1.4.1 independently of one another denote halogen, —NH 2 , —NH(C 1-4 -alkyl), —N(C 1-4 -alkyl) 2 or —SO 2 —R 1.1.2 ,R 1.2 denotes halogen, —NO 2 , —CN or phenyl,R 1.3 denotes (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —CO 2 R 1.1.1 , C 1-6 -alkyl,(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,R 1.4 independently of one another denote (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —S(O)—R 1.1.2 , —S(O) 2 —R 1.1.2 , —NR 1.1.3 R 1.1.4 , C 1-6 -alkyl,(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms , or(c) an oxo group,R 2 denotes (a) H or C 1-4 -alkyl,(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,R 3 independently of one another denote (a) H, halogen, —CN, —OH, C 1-6 -alkyl, C 3-7 -cycloalkyl, —O—C 1-4 -alkyl, —O—CF 3 , —O—C 3-6 -cycloalkyl, —N(C 1-3 -alkyl) 2 , —C(O)—NH 2 , —(SO 2 )NH 2 , —SO 2 —C 1-3 -alkyl,(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,R 4 , R 5 ,R 6 , R 7 ,R 8 independently of one another denote (a) H, halogen, —CN, —OH,(b) C 1-6 -alkyl, wherein two adjacent substituents together may denote a trimethylene or tetramethylene group,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(d) C 3-7 -cycloalkyl,(e) —O—C 1-6 -alkyl, wherein two adjacent substituents may denote a methylenedioxy or ethylenedioxy group,(f) —O—CF 3 , —O—C 3-7 -cycloalkyl,(g) —NH 2 , —NH(C 1-3 -alkyl), —N(C 1-3 -alkyl) 2 ,(h) —C(O)—R 8.1 ,(i) —SO 2 —R 8.2 ,(j) a five-membered heteroaryl group optionally substituted by one or two C 1-3 -alkyl groups which is selected from among pyrrolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, imidazolyl, pyrazolyl, triazolyl and tetrazolyl,(k) a six-membered heteroaryl group optionally substituted by one or two C 1-3 -alkyl groups which is selected from among pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl and triazinyl,R 8.1 denotes —NH 2 , —NH(C 1-6 -alkyl),—N(C 1-6 -alkyl) 2 , N-acetidinyl, N-pyrrolidinyl, N-piperidinyl, N-morpholinyl, —OH, —O—C 1-8 -alkyl, —O—C 3-7 -cycloalkyl,R 8.2 denotes —NH 2 , —NH(C 1-6 -alkyl),—N(C 1-6 -alkyl) 2 , N-acetidinyl, N-pyrrolidinyl, N-piperidinyl, N-morpholinyl andn denotes one of the numbers 0, 1, 2, 3 or 4, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of the above general formula I, wherein R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and n are defined as mentioned hereinbefore in the first embodiment and R 1 denotes (a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 ,(b) a C 1-3 -alkyl group wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(c) a C 3-6 -cycloalkyl group optionally substituted by a group R 1.2 ,(d) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.3 ,(e) a five-membered heteroaryl group optionally substituted by a group R 1.4 , which contains at least one N, O or S atom and which optionally additionally contains one, two or three further N atoms, or(f) a six-membered heteroaryl group optionally substituted by a group R 1.4 , which contains one, two or three N atoms,R 1.1 denotes C 3-6 -cycloalkyl, —OR 1.1.1 , —NR 1.1.3 R 1.1.4 , —C(O)—NR 1.1.3 R 1.1.4 , —CN, —CO 2 R 1.1.1 , —S(O) 2 —C 1-6 -alkyl or —O—S(O) 2 —C 1-6 -alkyl,R 1.1.1 denotes (a) H,(b) C 1-4 -alkyl,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or(d) C 3-6 -cycloalkyl,R 1.1.3 ,R 1.1.4 independently of one another denote (a) H,(b) C 1-4 -alkyl or(c) C 3-6 -cycloalkyl, andR 1.2 denotes halogen, —NO 2 , —CN or phenyl,R 1.3 denotes (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —CO 2 R 1.1.1 , C 1-6 -alkyl or(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, andR 1.4 denotes (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —NR 1.1.3 R 1.1.4 , C 1-6 -alkyl,(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or(c) an oxo group, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of the above general formula I, wherein R 1 denotes (a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 ,(b) a C 1-3 -alkyl group wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(c) a C 3-6 -cycloalkyl group optionally substituted by a group R 1.2 ,(d) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.3 ,(e) a five-membered heteroaryl group optionally substituted by a group R 1.4 , which contains at least one N, O or S atom and which optionally additionally contains one, two or three further N atoms, or(f) a six-membered heteroaryl group optionally substituted by a group R 1.4 , which contains one, two or three N atoms,R 1.1 denotes C 3-6 -cycloalkyl, —OR 1.1.1 , —NR 1.1.3 R 1.1.4 , —C(O)—NR 1.1.3 R 1.1.4 , —CN, —CO 2 R 1.1.1 , —S(O) 2 —C 1-6 -alkyl or —O—S(O) 2 —C 1-6 -alkyl,R 1.1.1 denotes (a) H,(b) C 14 -alkyl,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or(d) C 3-6 -cycloalkyl,R 1.1.3 ,R 1.1.4 independently of one another denote (a) H,(b) C 1-4 -alkyl or(c) C 3-6 -cycloalkyl,R 1.2 denotes halogen, —NO 2 , —CN or phenyl,R 1.3 denotes (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —CO 2 R 1.1.1 , C 1-6 -alkyl or(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,R 1.4 denotes (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —NR 1.1.3 R 1.1.4 , C 1-6 -alkyl,(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or(c) an oxo groupR 2 denotes H or C 1-3 -alkyl,R 3 independently of one another denote (a) H, halogen, C 1-3 -alkyl, —O—C 1-3 -alkyl or(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,R 4 denotes H or halogen,R 5 denotes (a) H, halogen,(b) C 1-3 -alkyl,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(d) —O—C 1-3 -alkyl,(e) —C(O)—O—C 1-3 -alkyl or —C(O)—NH 2 ,R 6 denotes (a) H, halogen,(b) C 1-3 -alkylene-R 6.1 ,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(d) —OH, —O—C 1-4 -alkyl,(e) —O—CHF 2 , —O—CF 3 ,(f) —C(O)—O—R 6.2 , —CN, —C(O)—CH 3 , —C(O)—NH 2 or(g) pyrrolyl,R 6.1 denotes H, —OH,R 6.2 denotes H, C 1-3 -alkyl,R 7 denotes (a) H, halogen,(b) C 1-3 -alkyl,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(d) —O—C 1-3 -alkyl,(e) —C(O)—NH 2 or —C(O)-pyrrolidinyl, andR 8 denotes (a) H, halogen,(b) C 1-4 -alkyl,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(d) —O—C 1-3 -alkyl,(e) —O—CF 3 ,(f) —CN, —C(O)—NH 2 or(g) pyrrolyl, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of the above general formula I, wherein R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and n are defined as mentioned hereinbefore in the first embodiment and R 1 denotes (a) a C 1-6 -alkyl group optionally substituted by a group R 1.1 ,(b) a C 1-3 -alkyl group wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(c) a phenyl group optionally substituted by 1, 2 or 3 groups R 1.3 ,(d) a five-membered heteroaryl group optionally substituted by a group R 1.4 , which is selected from among furanyl, isoxazolyl, isothiazolyl, oxazolyl, thiazolyl, pyrazolyl, thiadiazolyl, oxadiazolyl, triazolyl, tetrazolyl, imidazolyl, indolyl, thienyl, pyrrolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl and benzisoxazinyl, or(e) a six-membered heteroaryl group optionally substituted by a group R 1.4 , which is selected from among pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, quinazolinyl and quinoxazinyl,R 1.1 denotes C 3-6 -cycloalkyl, —OR 1.1.1 , —NR 1.1.3 R 1.1.4 , —C(O)—NR 1.1.3 R 1.1.4 , —CN, —CO 2 R 1.1.1 , —S(O) 2 —C 1-6 -alkyl or —O—S(O) 2 —C 1-6 -alkyl,R 1.1.1 denotes (a) H,(b) C 1-4 -alkyl,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or(d) C 3-6 -cycloalkyl,R 1.1.3 ,R 1.1.4 independently of one another denote (a) H,(b) C 1-4 -alkyl or(c) C 3-6 -cycloalkyl,R 1.3 denotes (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —CO 2 R 1.1.1 , C 1-6 -alkyl or(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, andR 1.4 denotes (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , C 1-6 -alkyl,(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or(c) an oxo group, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of the above general formula I, wherein R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and n are defined as mentioned hereinbefore in the first embodiment and R 1 denotes a group selected from the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of the above general formula I, wherein R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and n are defined as mentioned hereinbefore in the first embodiment and R 2 denotes H or C 1-3 -alkyl, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of the above general formula I, wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 7 , R 8 and n are defined as mentioned hereinbefore in the first embodiment and R 3 independently of one another denote (a) H, halogen, C 1-3 -alkyl, —O—C 1-3 -alkyl or(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of the above general formula I, wherein R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 and n are defined as mentioned hereinbefore in the first embodiment and R 4 denotes H or halogen, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of the above general formula I, wherein R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , R 8 and n are defined as mentioned hereinbefore in the first embodiment and R 5 denotes (a) H, halogen,(b) C 1-3 -alkyl,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(d) —O—C 1-3 -alkyl,(e) —C(O)—O—C 1-3 -alkyl or —C(O)—NH 2 , the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of the above general formula I, wherein R 1 , R 2 , R 3 , R 4 , K R 5 , R 7 , R 8 and n are defined as mentioned hereinbefore in the first embodiment and R 6 denotes (a) H, halogen,(b) C 1-3 -alkylene-R 6.1 ,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(d) —OH, —O—C 1-4 -alkyl,(e) —O—CHF 2 , —O—CF 3 ,(f) —C(O)—O—R 6.2 , —CN, —C(O)—CH 3 , —C(O)—NH 2 or(g) pyrrolyl,R 6.1 denotes H or —OH andR 6.2 denotes H or C 1-3 -alkyl, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of the above general formula I, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 8 and n are defined as mentioned hereinbefore in the first embodiment and R 7 denotes (a) H, halogen,(b) C 1-3 -alkyl,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(d) —O—C 1-3 -alkyl,(e) —C(O)—NH 2 or —C(O)-pyrrolidinyl, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of the above general formula I, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and n are defined as mentioned hereinbefore in the first embodiment and R 8 denotes (a) H, halogen,(b) C 1-4 -alkyl,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(d) —O—C 1-3 -alkyl,(e) —O—CF 3 ,(f) —CN, —C(O)—NH 2 or(g) pyrrolyl, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of the above general formula I wherein R 1 denotes a group selected from R 2 denotes H or —CH 3 ,R 3 denotes H, F, —CF 3 , —CH 3 or —O—CH 3 ,R 4 denotes H or Cl,R 5 denotes H, Cl, C 1-3 -alkyl, —CF 3 , —O—C 1-3 -alkyl, —C(O)—O—C 1-3 -alkyl or —C(O)—NH 2 ,R 6 denotes H, F, Cl, C 1-3 -alkyl, —CF 3 , —O—C 1-4 -alkyl, —OCF 3 , —C(O)—NH 2 or pyrrolyl,R 7 denotes H, F, Cl, C 1-3 -alkyl, —CF 3 , —O—C 1-3 -alkyl, —C(O)—NH 2 or —C(O)-pyrrolidinyl andR 8 denotes H, F, Cl, Br, C 1-4 -alkyl, —CF 3 , —O—C 1-3 -alkyl, —OCF 3 , —C(O)—NH 2 , —OCF 3 or pyrrolyl, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of the above general formula I wherein R 1 denotes a group selected from R 2 denotes H, —CH 3 or —C 2 H 5 ,R 3 denotes H, F, Cl, —CF 3 , —CH 3 or —O—CH 3 ,R 4 denotes H or Cl,R 5 denotes H, Cl, C 1-3 -alkyl, —CF 3 , —O—C 1-3 -alkyl, —C(O)—O—C 1-3 -alkyl or —C(O)—NH 2 ,R 6 denotes H, F, Cl, Br, —CN, C 1-3 -alkyl, —CF 3 , —COOH, —COO—C 1-3 -alkyl, —CH(OH)CH 3 , —OH, —O—C 1-4 -alkyl, —OCF 3 , —OCHF 2 , —C(O)—CH 3 , —C(O)—NH 2 or pyrrolyl,R 7 denotes H, F, Cl, C 1-3 -alkyl, —CF 3 , —O—C 1-3 -alkyl, —C(O)—NH 2 or —C(O)-pyrrolidinyl andR 8 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, —CF 3 , —O—C 1-3 -alkyl, —OCF 3 , —C(O)—NH 2 , —OCF 3 or pyrrolyl, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of general formula Ia, wherein R 1 denotes a C 1-6 -alkyl group optionally substituted by a group R 1.1 ,R 1.1 denotes halogen, —NO 2 , —CN, C 3-6 -cycloalkyl, —OR 1.1.1 , —SR 1.1.1 , —C(O)R 1.1.1 , —S(O) 2 —R 1.1.2 , —O—S(O) 2 —R 1.1.1 , —CO 2 R 1.1.1 , —O—C(O)—R 1.1.1 , —NR 1.1.3 R 1.1.4 , —NR 1.1,3- C(O)—R 1.1.1 , —NR 1.1,3- C(O)—R 1.1.1 , —NR 1.1,3- CO 2 —R 1.1.1 or —C(O)—NR 1.1.3 R 1.1.4 ,R 1.1.1 denotes (a) H,(b) C 1-4 -alkyl,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or(d) C 3-6 -cycloalkyl,R 1.1.2 denotes (a) C 1-4 -alkyl,(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or(c) —O—C 1-4 -alkyl,R 1.1.3 ,R 1.1.4 independently of one another denote (a) H,(b) a C 1-4 -alkyl group optionally substituted by 1, 2 or 3 groups R 1.1.4.1 or(c) C 3-6 -cycloalkyl,R 2 denotes (a) H, C 1-4 -alkyl or(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,R 4 denotes H or halogen,R 6 denotes (a) H, halogen,(b) C 1-3 -alkylene-R 6.1 ,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(d) —OH, —O—C 1-4 -alkyl,(e) —O—CHF 2 , —O—CF 3 ,(f) —C(O)—O—R 6.2 , —CN, —C(O)—CH 3 , —C(O)—NH 2 or(g) pyrrolyl,R 6.1 denotes H, —OH,R6.2 denotes H, C 1-3 -alkyl, andR 8 denotes (a) H, halogen,(b) C 1-4 -alkyl,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(d) —O—C 1-3 -alkyl,(e) —O—CF 3 ,(f) —CN, —C(O)—NH 2 or(g) pyrrolyl, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of general formula Ia, wherein R 1 denotes a group selected from R 2 denotes H, —CH 3 or —C 2 H 5 ,R 4 denotes H or Cl,R 6 denotes Cl or —O—C 1-4 -alkyl, andR 8 denotes F or —CF 3 , the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of general formula Ia, wherein R 1 denotes (a) a five-membered heteroaryl group optionally substituted by 1, 2 or 3 groups R 1.4 , which contains at least one N, O or S atom and which optionally additionally contains one, two or three further N atoms and which may additionally be benzo-condensed, or(b) a six-membered heteroaryl group optionally substituted by a group R 1.4 , which contains one, two or three N atoms and which may additionally be benzo-condensed,R 1.4 independently of one another denote (a) halogen, —NO 2 , —CN, —OR 1.1.1 , —SR 1.1.1 , —S(O) 2 —R 1.1.2 , —S(O) 2 —R 1.1.2 , —NR 1.1.3 R 1.1.4 , C 1-6 -alkyl or(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,R 1.1.1 denotes (a) H,(b) C 1-4 -alkyl,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or(d) C 3-6 -cycloalkyl,R 1.1.2 denotes (a) C 1-4 -alkyl,(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or(c) —O—C 1-4 -alkyl,R 1.1.3 ,R 1.1.4 independently of one another denote (a) H,(b) a C 1-4 -alkyl group optionally substituted by 1, 2 or 3 groups R 1.1.4.1 ,(c) C 3-6 -cycloalkyl, orR 2 denotes (a) H, C 1-4 -alkyl or(b) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,R 4 denotes H or halogen,R 6 denotes (a) H, halogen,(b) C 1-3 -alkylene-R 6.1 ,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(d) —OH, —O—C 1-4 -alkyl,(e) —O—CHF 2 , —O—CF 3 ,(f) —C(O)—O—R 6.2 , —CN, —C(O)—CH 3 , —C(O)—NH 2 or(g) pyrrolyl,R 6.1 denotes H, —OH,R 6.2 denotes H, C 1-3 -alkyl, andR 8 denotes (a) H, halogen,(b) C 1-4 -alkyl,(c) C 1-3 -alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,(d) —O—C 1-3 -alkyl,(e) —O—CF 3 ,(f) —CN, —C(O)—NH 2 or(g) pyrrolyl, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. A further embodiment of the present invention comprises the compounds of general formula Ia, wherein R 1 denotes a group selected from R 2 denotes H, —CH 3 or —C 2 H 5 ,R 4 denotes H or Cl,R 6 denotes F, Cl, Br, —CN, —CH 3 , —CF 3 , —COOH, —COO—CH 3 , —CH(OH)CH 3 , —OH, —O—CH 3 , —OCF 3 , —OCHF 2 , —C(O)—CH 3 , —C(O)—NH 2 or pyrrolyl, andR 8 denotes H, F, Cl, Br, —CN, C 1-4 -alkyl, —CF 3 , —O—C 1-3 -alkyl, —OCF 3 , —C(O)—NH 2 , —OCF 3 or pyrrolyl, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. The following are mentioned as examples of most particularly preferred compounds of the above general formula I: No.Structure(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108)(109)(110)(111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121)(122)(123)(124)(125)(126)(127)(128)(129)(130)(131)(132)(133)(134)(135)(136)(137)(138)(139)(140)(141)(142)(143)(144)(145)(146)(147)(148)(149)(150)(151)(152)(153)(154)(155)(156)(157)(158)(159)(160)(161)(162)(163) the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases. Terms and Definitions Used Unless otherwise stated, all the substituents are independent of one another. If for example there are a plurality of C 1-6 -alkyl groups as substituents in one group, in the case of three C 1-6 -alkyl substituents, independently of one another, one may represent methyl, one n-propyl and one tert-butyl. Within the scope of this application, in the definition of possible substituents, these may also be represented in the form of a structural formula. If present, an asterisk (*) in the structural formula of the substituent is to be understood as being the linking point to the rest of the molecule. The subject-matter of this invention also includes the compounds according to the invention, including the salts thereof, wherein one or more hydrogen atoms, for example one, two, three, four or five hydrogen atoms, are replaced by deuterium. By the term “C 1-3 -alkyl” (including those which are part of other groups) are meant alkyl groups with 1 to 3 carbon atoms, by the term “C 1-4 -alkyl” are meant branched and unbranched alkyl groups with 1 to 4 carbon atoms, by the term “C 1-6 -alkyl” are meant branched and unbranched alkyl groups with 1 to 6 carbon atoms and by the term “C 1-8 -alkyl” are meant branched and unbranched alkyl groups with 1 to 8 carbon atoms. Examples of these include: methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, neopentyl, n-hexyl, n-heptyl and n-octyl. The abbreviations Me, Et, n-Pr, i-Pr, n-Bu, i-Bu, t-Bu, etc. may optionally also be used for the groups mentioned above. Unless stated otherwise, the definitions propyl and butyl include all the possible isomeric forms of the groups in question. Thus, for example, propyl includes n-propyl and iso-propyl, butyl includes iso-butyl, sec-butyl and tert-butyl. Moreover the terms mentioned above also include those groups wherein each methylene group may be substituted by up to two fluorine atoms and each methyl group may be substituted by up to three fluorine atoms. By the term “C 0-2 -alkylene” are meant branched and unbranched alkylene groups with 0 to 2 carbon atoms, while a C 0 -alkylene group denotes a bond. Examples of these include: methylene, ethylene and ethane-1,1-diyl. Moreover the terms mentioned above also include those groups wherein each methylene group may be substituted by up to two fluorine atoms. By the term “C 3-7 -cycloalkyl” (including those which are part of other groups) are meant cyclic alkyl groups with 3 to 7 carbon atoms and by the term “C 3-6 -cycloalkyl” are meant cyclic alkyl groups with 3 to 6 carbon atoms. Examples of these include: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl. Unless otherwise stated, the cyclic alkyl groups may be substituted by one or more groups selected from among methyl, ethyl, iso-propyl, tert-butyl, hydroxy, fluorine, chlorine, bromine and iodine. By the term “C 2-6 -alkenyl” (including those which are part of other groups) are meant branched and unbranched alkenyl groups with 2 to 6 carbon atoms, provided that they have at least one double bond. Alkenyl groups with 2 to 4 carbon atoms are preferred. Examples of these include: ethenyl or vinyl, propenyl, butenyl, pentenyl, or hexenyl. Unless stated otherwise, the definitions propenyl, butenyl, pentenyl and hexenyl include all the possible isomeric forms of the groups in question. Thus, for example, propenyl includes 1-propenyl and 2-propenyl, butenyl includes 1-butenyl, 2-butenyl and 3-butenyl, 1-methyl-1-propenyl, 1-methyl-2-propenyl etc. By the term “C 2-6 -alkynyl” (including those which are part of other groups) are meant branched and unbranched alkynyl groups with 2 to 6 carbon atoms, provided that they have at least one triple bond. Alkynyl groups with 2 to 4 carbon atoms are preferred. Examples of these include: ethynyl, propynyl, butynyl, pentynyl or hexynyl. Unless stated otherwise, the definitions propynyl, butynyl, pentynyl and hexynyl include all the possible isomeric forms of the groups in question. Thus, for example, propynyl includes 1-propynyl and 2-propynyl, butynyl includes 1-butynyl, 2-butynyl and 3-butynyl, 1-methyl-1-propynyl, 1-methyl-2-propynyl etc. “Halogen” within the scope of the present invention denotes fluorine, chlorine, bromine or iodine. Unless stated otherwise, fluorine, chlorine and bromine are regarded as preferred halogens. By the term “heterocyclic rings” are meant stable 4-, 5- or 6-membered monocyclic heterocyclic ring systems which may be both saturated and monounsaturated and besides carbon atoms may carry one or two heteroatoms which are selected from among nitrogen, oxygen and sulphur. Both nitrogen and sulphur heteroatoms may optionally be oxidised. The previously mentioned heterocycles may be linked to the rest of the molecule via a carbon atom or a nitrogen atom. The following compounds are mentioned by way of example: “Cyclic imides” include for example succinimide, maleimide and phthalimide. By the term “aryl” (including those which are part of other groups) are meant aromatic ring systems with 6 or 10 carbon atoms. Examples of these include phenyl, 1-naphthyl or 2-naphthyl; the preferred aryl group is phenyl. Unless otherwise stated, the aromatic groups may be substituted by one or more groups selected from among methyl, ethyl, n-propyl, iso-propyl, tert-butyl, hydroxy, methoxy, trifluoromethoxy, fluorine, chlorine, bromine and iodine, while the groups may be identical or different. By the term “heteroaryl” are meant five- or six-membered heterocyclic aromatic groups which may contain one, two, three or four heteroatoms, selected from among oxygen, sulphur and nitrogen, and which additionally contain sufficient conjugated double bonds to form an aromatic system. These heteroaryls may additionally be benzo-fused to a phenyl ring, so that nine- or ten-membered bicyclic heteroaryls are formed. The following are examples of five- or six-membered heterocyclic aromatic groups: The following are examples of nine- or ten-membered heterocyclic aromatic groups: Unless otherwise stated, the heteroaryls mentioned previously may be substituted by one or more groups selected from among methyl, ethyl, n-propyl, iso-propyl, tert-butyl, hydroxy, methoxy, trifluoromethoxy, fluorine, chlorine, bromine and iodine, while the groups may be identical or different. In addition, a nitrogen atom present in the heteroaryl group may be oxidised, thus forming an N-oxide. By the term “oxo group” is meant an oxygen substituent at a carbon atom, which leads to the formation of a carbonyl group —C(O)—. The introduction of an oxo group as substituent at a non-aromatic carbon atom leads to the conversion of a —CH 2 group into a —C(O) group. The introduction of an oxo group at an aromatic carbon atom leads to the conversion of a —CH group into a —C(O) group and result in the loss of aromaticity. If they contain suitable basic functions, for example amino groups, compounds of general formula I may be converted, particularly for pharmaceutical use, into the physiologically acceptable salts thereof with inorganic or organic acids. Examples of inorganic acids for this purpose include hydrobromic acid, phosphoric acid, nitric acid, hydrochloric acid, sulphuric acid, methanesulphonic acid, ethanesulphonic acid, benzenesulphonic acid or p-toluenesulphonic acid, while organic acids that may be used include malic acid, succinic acid, acetic acid, fumaric acid, maleic acid, mandelic acid, lactic acid, tartaric acid or citric acid. In addition, the compounds of general formula I, if they contain suitable carboxylic acid functions, may if desired be converted into the addition salts thereof with inorganic or organic bases. Examples of inorganic bases include alkali or alkaline earth metal hydroxides, e.g. sodium hydroxide or potassium hydroxide, or carbonates, ammonia, zinc or ammonium hydroxides; examples of organic amines include diethylamine, triethylamine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine or dicyclohexylamine. The compounds according to the invention may be present as racemates, provided that they have only one chiral element, but may also be obtained as pure enantiomers, i.e. in the (R) or (S) form. However, the application also includes the individual diastereomeric pairs of antipodes or mixtures thereof, which are obtained if there is more than one chiral element in the compounds of general formula I, as well as the individual optically active enantiomers of which the above-mentioned racemates are made up. Methods of Preparation According to the invention the compounds of general formula I are obtained by methods known per se to those skilled in the art, for example by the following methods: (A) amide coupling: (B) amide coupling: (C) reductive amination of the aldehydes or ketones; reduction of the oximes previously formed from the aldehydes or ketones: (D) nucleophilic substitution at 4-fluoro-aldehydes or ketones: (E) reduction of the nitrile arouo: (F) nucleophilic substitution at 4-fluoro-benzonitriles: Description of the Method of hBK1 Receptor Binding CHO cells expressing the hBK1 receptor are cultivated in Dulbecco's modified medium. The medium from confluent cultures is removed and the cells are washed with PBS buffer, scraped off and isolated by centrifugation. The cells are then homogenized in suspension and the homogenate is centrifuged and resuspended. The protein content is determined and the membrane preparation obtained in this manner is then frozen at −80° C. After thawing, 200 μl of the homogenate (50 to 100 μg of proteins/assay) are incubated at room temperature with 0.5 to 1.0 nM of kallidin (DesArg10, Leu9), [3,4-prolyl-3,43H(N)] and increasing concentrations of the test substance in a total volume of 250 μl for 60 minutes. The incubation is terminated by rapid filtration through GF/B glass fibre filters which had been pretreated with polyethyleneimine (0.3%). The protein-bound radioactivity is measured in a TopCount NXT. Non-specific binding is defined as radioactivity bound in the presence of 1.0 μM of kallidin (DesArg10, Leu9), [3,4-prolyl-3,43H(N)]. The concentration/binding curve is analysed using a computer-assisted nonlinear curve fitting. The K i which corresponds to the test substance is determined using the data obtained in this manner. Indications By virtue of their pharmacological properties, the novel compounds and their physiologically acceptable salts are suitable for treating diseases and symptoms of diseases caused at least to some extent by stimulation of bradykinin-B1 receptors. In view of their pharmacological effect the substances are suitable for the treatment of (a) acute pain such as e.g. toothache, peri- and postoperative pain, traumatic pain, muscle pain, the pain caused by burns, sunburn, trigeminal neuralgia, pain caused by colic, as well as spasms of the gastro-intestinal tract or uterus;(b) visceral pain such as e.g. chronic pelvic pain, gynaecological pain, pain before and during menstruation, pain caused by pancreatitis, peptic ulcers, interstitial cystitis, renal colic, angina pectoris, pain caused by irritable bowel, non-ulcerative dyspepsia and gastritis, non-cardiac thoracic pain and pain caused by myocardial ischaemia and cardiac infarct;(c) neuropathic pain such as e.g. painful neuropathies, pain of diabetic neuropathy, AIDS-associated neuropathic pain, pain of lumbago, non-herpes-associated neuralgia, post-zoster neuralgia, nerve damage, cerebro-cranial trauma, pain of nerve damage caused by toxins or chemotherapy, phantom pain, pain of multiple sclerosis, nerve root tears and painful traumatically-caused damage to individual nerves;(d) inflammatory/pain receptor-mediated pain in connection with diseases such as osteoarthritis, rheumatoid arthritis, rheumatic fever, tendo-synovitis, tendonitis, gout, vulvodynia, damage to and diseases of the muscles and fascia (muscle injury, fibromyalgia), osteoarthritis, juvenile arthritis, spondylitis, gout-arthritis, psoriasis-arthritis, fibromyalgia, myositis, migraine, dental disease, influenza and other virus infections such as colds, systemic lupus erythematodes,(e) tumour pain associated with cancers such as lymphatid or myeloid leukaemia, Hodgkin's disease, non-Hodgkin's lymphomas, lymphogranulomatosis, lymphosarcomas, solid malignant tumours and extensive metastases;(f) headache diseases such as e.g. headache of various origins, cluster headaches, migraine (with or without aura) and tension headaches. The compounds are also suitable for treating (g) inflammatory changes connected with diseases of the airways such as bronchial asthma, including allergic asthma (atopic and non-atopic) as well as bronchospasm on exertion, occupationally induced asthma, viral or bacterial exacerbation of an existing asthma and other non-allergically induced asthmatic diseases;chronic obstructive pulmonary disease (COPD) including pulmonary emphysema, acute adult respiratory distress syndrome (ARDS), bronchitis, lung inflammation, allergic rhinitis (seasonal and all year round), vasomotor rhinitis and diseases caused by dust in the lungs such as aluminosis, anthracosis, asbestosis, chalicosis, siderosis, silicosis, tabacosis and byssinosis;(h) inflammatory phenomena caused by sunburn and burns, oedema after burns trauma, cerebral oedema and angiooedema, intestinal complaints including Crohn's diseases and ulcerative colitis, irritable bowel syndrome, pancreatitis, nephritis, cystitis (interstitial cystitis), uveitis; inflammatory skin diseases (such as e.g. psoriasis and eczema), vascular diseases of the connective tissue, lupus, sprains and fractures;(i) diabetes mellitus and its effects (such as e.g. diabetic vasculopathy, diabetic neuropathy, diabetic retinopathy) and diabetic symptoms in insulitis (e.g. hyperglycaemia, diuresis, proteinuria and increased renal excretion of nitrite and kallikrein);(j) neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease;(k) sepsis and septic shock after bacterial infections or after trauma;(l) syndromes that cause itching and allergic skin reactions;(m) osteoporosis;(n) epilepsy;(o) damage to the central nervous system;(p) wounds and tissue damage;(q) inflammation of the gums;(r) benign prostatic hyperplasia and hyperactive bladder;(s) pruritus;(t) vitiligo;(u) disorders of the motility of respiratory, genito-urinary, gastro-intestinal or vascular regions and(v) post-operative fever. By the term “treatment” or “therapy” is meant a therapeutic treatment of patients with manifest, acute or chronic indications, this term including on the one hand symptomatic (palliative) treatment for relieving the symptoms of the disease and on the other hand the causal or curative treatment of the indication with the aim of bringing an end to the pathological condition, reducing the severity of the pathological condition or delaying the progress of the pathological condition, irrespective of the nature or gravity of the indication. In another aspect the present invention relates to the use of a compound of general formula I for preparing a pharmaceutical composition for the acute and prophylactic treatment of acute pain, visceral pain, neuropathic pain, inflammatory pain or pain mediated by pain receptors, cancer pain and headache diseases. The use is characterised in that it comprises administering an effective amount of a compound of general formula I or a physiologically acceptable salt thereof to a patient requiring such treatment. In addition to being suitable as human therapeutic agents, these substances are also useful in the veterinary treatment of domestic animals, exotic animals and farm animals. Combinations For treating pain, it may be advantageous to combine the compounds according to the invention with stimulating substances such as caffeine or other pain-alleviating active compounds. If active compounds suitable for treating the cause of the pain are available, these can be combined with the compounds according to the invention. If, independently of the pain treatment, other medical treatments are also indicated, for example for high blood pressure or diabetes, the active compounds required can be combined with the compounds according to the invention. The following compounds may be used for combination therapy, for example: Non-steroidal antirheumatics (NSAR): COX-2 inhibitors such as propionic acid derivatives (alminoprofen, benoxaprofen, bucloxic acid, carprofen, fenhufen, fenoprofen, fiuprofen, fiulbiprofen, ibuprofen, indoprofen, ketoprofen, miroprofen, naproxen, oxaprozin, pirprofen, pranoprofen, suprofen, tiaprofenic acid, tioxaprofen), acetic acid derivatives (indomethacin, acemetacin, alcofenac, isoxepac, oxpinax, sulindac, tiopinac, tolmetin, zidometacin, zomepirac) fenamic derivatives (meclofenamic acid, mefenamic acid, tolfenamic acid), biphenyl-carboxylic acid derivatives, oxicams (isoxicam, meloxicam, piroxicam, sudoxicam and tenoxicam), salicylic acid derivatives (acetylsalicylic acid, sulphasalazin, why not also mesalazin, olsalazin, and pyrazolone (apazone, bezpiperylone, feprazone, mofebutazone, oxyphenbutazone, phenylbutazone, why not also propyphenazone and metamizol, and coxibs (celecoxib, valecoxib, rofecoxib, etoricoxib). Opiate receptor agonists such as e.g. morphine, propoxyphen (Darvon), tramadol, buprenorphine. Cannabinoid agonists such as e.g. GW-1000, KDS-2000, SAB-378, SP-104, NVP001-GW-843166, GW-842166X, PRS-211375. Sodium channel blockers such as e.g. carbamazepine, mexiletin, lamotrigin, pregabalin, tectin, NW-1029, CGX-1002. N-type calcium channel blockers such as e.g. ziconitide, NMED-160, SP1-860. Serotonergic and noradrenergic modulators such as e.g. SR-57746, paroxetine, duloxetine, clonidine, amitriptyline, citalopram. Corticosteroids such as e.g. betamethasone, budesonide, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone and triamcinolone. Histamine H1-receptor antagonists such as e.g. bromopheniramine, chloropheniramine, dexchlorpheniramine, triprolidine, clemastine, diphenhydramine, diphenylpyraline, tripelennamine, hydroxyzine, methdilazine, promethazine, trimeprazine azatadine, cyproheptadine, antazoline, pheniramine, pyrilamine, astemizole, terfenadine, loratadine, cetirizine, desloratadine, fexofenadine, levocetirizine. Histamine H2-receptor antagonists such as e.g. cimetidine, famotidine, and ranitidine. Proton pump inhibitors such as e.g. omeprazole, pantoprazole, esomeprazole. Leukotriene antagonists and 5-lipoxygenasehemmer such as e.g. zafirlukast, montelukast, pranlukast and zileuton. Local anaesthetics such as e.g. Ambroxol, lidocaine. VR1 agonists and antagonists such as e.g. NGX-4010, WL-1002, ALGRX-4975, WL-10001, AMG-517. Nicotine receptor agonists such as e.g. ABT-202, A-366833, ABT-594, BTG-102, A-85380, CGX1204. P2X3-receptor antagonists such as e.g. A-317491, ISIS-13920, AZD-9056. NGF agonists and antagonists such as e.g. RI-724, RI-1024, AMG-819, AMG-403, PPH 207. NK1 and NK2 antagonists such as e.g. DA-5018, R-116301, CP-728663, ZD-2249. NMDA antagonists such as e.g. NER-MD-11, CNS-5161, EAA-090, AZ-756, CNP-3381. potassium channel modulators such as e.g. CL-888, ICA-69673, retigabin. GABA modulators such as e.g. lacosamide. Serotonergic and noradrenergic modulators such as e.g. SR-57746, paroxetine, duloxetine, clonidine, amitriptyline, citalopram, flibanserine. Anti-migraine drugs such as e.g. sumatriptan, zolmitriptan, naratriptan, eletriptan. The dosage necessary for obtaining a pain-alleviating effect is, in the case of intravenous administration, expediently from 0.01 to 3 mg/kg of body weight, preferably from 0.1 to 1 mg/kg, and, in the case of oral administration, from 0.1 to 8 mg/kg of body weight, preferably from 0.5 to 3 mg/kg, in each case 1 to 3 times per day. The compounds prepared according to the invention can be administered intravenously, subcutaneously, intramuscularly, intrarectally, intranasally, by inhalation, transdermally or orally, aerosol formulations being particularly suitable for inhalation. They can be incorporated into customary pharmaceutical preparations, such as tablets, coated tablets, capsules, powders, suspensions, solutions, metered-dose aerosols or suppositories, if appropriate together with one or more customary inert carriers and/or diluents, for example with maize starch, lactose, cane sugar, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water/ethanol, water/glycerol, water/sorbitol, water/polyethylene glycol, propylene glycol, cetylstearyl alcohol, carboxymethylcellulose or fatty substances, such as hardened fat, or suitable mixtures thereof. Experimental Section Generally, there are mass spectra and/or 1 H NMR spectra for the compounds that were prepared. The ratios given for the eluants are in volume units of the solvents in question. For ammonia, the given volume units are based on a concentrated solution of ammonia in water. Unless indicated otherwise, the acid, base and salt solutions used for working up the reaction solutions are aqueous systems having the stated concentrations. For chromatographic purification, silica gel from Millipore (MATREX™, 35 to 70 μm) or Alox (E. Merck, Darmstadt, Alumina 90 standardized, 63 to 200 μm, article No. 1.01097.9050) are used. In the descriptions of the experiments, the following abbreviations are used: TLC thin layer chromatogramDIPEA diisopropylethylamineDMA N,N-dimethylacetamideDMAP 4-dimethylaminopyridineDMF N,N-dimethylformamideDMSO dimethylsulphoxideHATU O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphatetert tertiaryTBTU 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium-tetrafluoroborateTHF tetrahydrofuran The following analytical HPLC methods were used: Method 1: Column: XTerra™ MS C18, 2.5 μM, 4.6×30 mm Detection: 210-420 nmEluant A: water/0.1% formic acidEluant B: acetonitrile/0.1% formic acidGradient: time in min% A% Bflow rate in mL/min0.095.05.01.00.195.05.01.03.12.098.01.04.52.098.01.05.095.05.01.0 Method 2: Column: Microsorb C18, 3 μM, 4.6×50 mm Detection: 220-320 nmEluant A: water/0.1% TFAEluant B: acetonitrile/0.1% TFAGradient: time in min% A% Bflow rate in mL/min0.095.05.01.50.595.05.01.53.82.098.01.54.32.098.01.54.3595.05.01.54.695.05.01.5 Method 3: Column: XTerra™ MS C18, 3.5 μM, 4.6×50 mm Detection: 210-420 nmEluant A: water/0.1% formic acidEluant B: acetonitrile/0.1% formic acidGradient: time in min% A% Bflow rate in mL/min0.095.05.01.00.195.05.01.07.12.098.01.07.92.098.01.08.095.05.01.0 Method 4: Column: Zorbax Stable Bond C18, 3.5 μM, 4.6×75 mm Detection: 230-360 nmEluant A: water/0.1% formic acidEluant B: acetonitrile/0.1% formic acidGradient: time in min% A% Bflow rate in mL/min0.095.05.01.60.195.05.01.64.510.090.01.65.0910.090.01.65.590.010.01.6 Method 5: Column: Interchim Strategy C18, 5 μM, 4.6×50 mm Detection: 220-320 nmEluant A: water/0.1% TFAEluant B: acetonitrileGradient: time in min% A% Bflow rate in mL/min0.095.05.03.00.395.05.03.02.02.098.03.02.42.098.03.02.4595.05.03.02.895.05.03.0 Method 6: Column: Merck Cromolith Speed ROD RP18e, 4.6×50 mm Detection: 190-400 nmEluant A: water/0.1% formic acidEluant B: acetonitrile/0.1% formic acidGradient: time in min% A% Bflow rate in mL/min0.090.010.01.54.510.090.01.55.010.090.01.55.590.010.01.5 The following preparative methods were used for the reversed-phase chromatography: Method 1: Column: AXIA Gemini C18 10 μM, 100×30 mm Detection: 210-500 nmEluant A: water/0.1% trifluoroacetic acidEluant B: acetonitrileGradient: time in min% A% Bflow rate in mL/min0.090.010.0500.690.010.0501.590.010.0508.05.095.0509.05.095.0509.290.010.05010.090.010.050 Method 2: Column: Atlantis C18 5 μM, 100×30 mm Detection: 210-500 nmEluant A: water/0.1% trifluoroacetic acidEluant B: acetonitrileGradient: time in min% A% Bflow rate in mL/min0.095.05.050.595.05.0508.05.095.0509.05.095.0509.595.05.05010.095.05.05010.195.05.05 The following microwave apparatus was used: Biotage EmrysOptimizer™, OEM Explorer™, CEM Discover™ EXAMPLE 1 Pyrimidine-5-carboxylic acid{1-[4-(4-chloro-2-fluoro-phenoxy)-3-fluoro-benzylcarbamoyl]-cyclopropyl}-amide 1a) ethyl 1-[(pyrimidine-5-carbonyl)-amino]-cyclopropanecarboxylate A solution of 6.80 g (54.8 mmol) of pyrimidine-5-carboxylic acid, 18.82 mL (135 mmol) of triethylamine and 19.27 g (60 mmol) of TBTU in 200 mL THF was stirred for 30 minutes at ambient temperature. Then 9.11 g (55 mmol) of ethyl 1-amino-cyclopropanecarboxylate hydrochloride were added and the mixture was stirred further overnight. Then the mixture was evaporated down, the residue was stirred with 200 mL water and the crude product was extracted with ethyl acetate. The intermediate product was purified by column chromatography (silica gel, dichloromethane+0-4% methanol). Yield: 88% of theory C 11 H 13 N 3 O 3 (235.24) Mass spectrum: [M+H] + =236 1b) 1-[(pyrimidine-5-carbonyl)-amino]-cyclopropanecarboxylic acid 65 mL of a 2N sodium hydroxide solution were added to a solution of 11.0 g (46.76 mmol) of ethyl 1-[(pyrimidine-5-carbonyl)amino]-cyclopropanecarboxylate in 200 mL methanol and the mixture was stirred for one hour at 50° C. Then it was neutralised with concentrated acetic acid and evaporated to dryness in vacuo. The crude product thus obtained was purified by chromatography. Yield: 52% of theory C 9 H 9 N 3 O 3 (207.19) Mass spectrum: [M+H] + =208 [M−H] − =206 1c) 4-(4-chloro-2-fluoro-phenoxy)-3-fluoro-benzonitrile A solution of 1.6 mL (15 mmol) of 4-chloro-2-fluorophenol and 1.68 g (15 mmol) of potassium tert. butoxide in 10 mL DMSO was stirred for one hour at ambient temperature. Then 2.1 g (15 mmol) of 3,4-difluoro-benzonitrile were added and the mixture was stirred overnight at 60° C. The mixture was then combined with approx. 50 mL water, then extracted three times with 30 ml of ethyl acetate. The organic extracts were washed with sodium chloride solution, dried on sodium sulphate and evaporated down. The product thus obtained was reacted further without any further purification. Yield: 98% of theory. C 13 H 6 ClF 2 NO (265.64) R f =0.90 thin layer chromatography (silica gel, dichloromethane+ethanol 50:1): 1d) 4-(4-chloro-2-fluoro-phenoxy)-3-fluoro-benzylamine 1.0 g (3.76 mmol) of 4-(4-chloro-2-fluoro-phenoxy)-3-fluoro-benzonitrile were hydrogenated in 30 mL methanolic ammonia solution with the addition of Raney nickel at 50° C. under a hydrogen pressure of 50 psi. Then the catalyst was filtered off and the filtrate was evaporated to dryness. The crude product thus obtained was reacted further without any further purification. Yield: 99% of theory C 13 H 10 ClF 2 NO (269.67) Mass spectrum: [M+H] + =270/72 1e) Pyrimidine-5-carboxylic acid-{1-[4-(4-chloro-2-fluoro-phenoxy)-3-fluoro-benzylcarbamoyl]-cyclopropyl}-amide hydrochloride 0.5 mL (3.6 mmol) of triethylamine, 0.433 g (1.35 mmol) of TBTU and 325.5 mg (1.2 mmol) of 4-(4-chloro-2-fluoro-phenoxy)-3-fluoro-benzylamine were added to a solution of 250 mg (1.2 mmol) of 1-[(pyrimidine-5-carbonyl)-amino]-cyclopropanecarboxylic acid (from 1b) in 15 mL tetrahydrofuran and the mixture was stirred overnight at ambient temperature. Then the mixture was evaporated to dryness and the crude product thus obtained was purified by chromatography. The purified product was dissolved in approx. 4 mL ethyl acetate and the dropwise addition of ethereal hydrochloric acid solution caused the hydrochloride to precipitate out, which was then filtered off and dried. Yield: 56% of theory C 22 H 17 ClF 2 N 4 O 3 ×HCl (496.31) Mass spectrum: [M−H] − =457/59 Thin layer chromatography (silica gel, dichloromethane+ethanol 9:1): R f =0.48 EXAMPLE 2 Pyrimidine-5-carboxylic acid-(1-{1-[4-(4-chloro-2-fluoro-phenoxy)-phenyl]-ethylcarbamoyl}-cyclopropyl)-amide 2a) 1-[4-(4-chloro-2-fluoro-phenoxy)-phenyl]-ethanone A solution of 2.45 g (17.7 mmol) of 4-fluoro-acetophenone and 2.60 g (17.7 mmol) of 4-chloro-2-fluorophenol in 40 mL DMSO was combined with 8.0 g (57.9 mmol) of potassium carbonate and the mixture was stirred for 32 hours at 120° C. Then it was evaporated to dryness in vacuo, the residue was combined with approx. 50 mL water and extracted three times with 40 mL methyl acetate. The extracts were washed with 2N potassium carbonate solution, dried on sodium sulphate and evaporated down. The crude product thus obtained was purified by column chromatography (silica gel, dichloromethane). Yield: 72% of theory C 14 H 10 ClFC 2 (264.68) Mass spectrum: [M+H] + =265 R f =0.18 thin layer chromatography (aluminium oxide, petroleum ether+dichloromethane 4:1) 2b) 1-[4-(4-chloro-2-fluoro-phenoxy)-phenyl]-ethanone-oxime A mixture of 3.4 g (12.8 mmol) of 1-[4-(4-chloro-2-fluoro-phenoxy)-phenyl]-ethanone and 3.0 mL hydroxylamine solution (50% in water) in 100 mL ethanol was refluxed for five hours. Then the mixture was evaporated to dryness, the residue was combined with approx. 15 mL water and extracted three times with 10 mL ethyl acetate. The extracts were washed with saturated sodium chloride solution, dried and evaporated down. The product thus obtained was reacted further without any further purification. Yield: 72% of theory C 14 H 11 ClFNO 2 (279.69) Mass spectrum: [M+H] + =280 R f =0.55 thin layer chromatography (silica gel, dichloromethane+methanol 50:1) 2c) 1-[4-(4-chloro-2-fluoro-phenoxy)-phenyl]-ethylamine 2.60 g (9.3 mmol) of 1-[4-(4-chloro-2-fluoro-phenoxy)-phenyl]-ethanone-oxime were dissolved in 20 mL methanol, then combined with 30 mL 7N methanolic ammonia solution and after the addition of 0.2 g Raney nickel hydrogenated at ambient temperature and 50 psi hydrogen pressure. Then the catalyst was filtered off and the filtrate was evaporated down. The crude product thus obtained was reacted further without any further purification. Yield: 89% of theory C 14 H 13 ClFNO (265.71) Mass spectrum: [M−NH 2 ] + =249/51 R f =0.36 thin layer chromatography (silica gel, dichloromethane+methanol 9:1) 2d) pyrimidine-5-carboxylic acid-(1-{1-[4-(4-chloro-2-fluoro-phenoxy)-phenyl]-ethylcarbamoyl}-cyclopropyl)-amide Analogously to Example (1e) the title compound was prepared from 1-[(pyrimidine-5-carbonyl)-amino]-cyclopropanecarboxylic acid and 1-[4-(4-chloro-2-fluoro-phenoxy)-phenyl]-ethylamine. Yield: 29% of theory C 23 H 20 ClFN 4 O 3 (454.88) Mass spectrum: [M+H] + =455/57 R f =0.44 thin layer chromatography (silica gel, dichloromethane+methanol 9:1) EXAMPLE 7 Pyrimidine-5-carboxylic acid{1-[3-fluoro-4-(4-methoxy-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 7a) 3-fluoro-4-(4-methoxy-phenoxy)-benzaldehyde 4.9 g (40 mmol) of 4-methoxy-phenol and 4.4 ml (40 mmol) of 3,4-difluorobenzaldehyde were dissolved in 40 ml DMA and stirred in a microwave (CEM Explorer) for 15 minutes at 110° C., then filtered through basic Alox, washed with DMF and concentrated by rotary evaporation. The residue was separated through a KG column with a gradient (cyclohexane+10-25% ethyl acetate) and concentrated by rotary evaporation. Yield: 57% of theory C 14 H 11 FO 3 (246.24) Mass spectrum: [M+H] + =247 7b) 3-fluoro-4-(4-methoxy-phenoxy)-benzylamine 73.9 mg (0.3 mmol) of 3-fluoro-4-(4-methoxy-phenoxy)-benzaldehyde are dissolved in 5 ml of methanolic ammonia, combined with Ra—Ni and shaken for about 9 hours at 35° C. and 3 bar H 2 pressure. The catalyst was removed by suction filtering and the solution was evaporated down in vacuo, dissolved in 3 ml DMF and purified by chromatography. Yield: 67% of theory C 14 H 14 FNO 2 (247.27) Mass spectrum: [M−NH 2 ] + =231 7c) pyrimidine-5-carboxylic acid-{1-[3-fluoro-4-(4-methoxy-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 24.7 mg (0.1 mmol) of 3-fluoro-4-(4-methoxy-phenoxy)-benzylamine were dissolved in 1 ml DMF. 20.7 mg (0.1 mmol) of 1-[(pyrimidine-5-carbonyl)-amino]-cyclopropanecarboxylic acid (prepared in 1b) were also dissolved in DMF and 35.3 mg (0.11 mmol) and 21 μl triethylamine (0.15 mmol) were added. Shaken overnight at ambient temperature and purified by reversed-phase chromatography. Yield: 65% of theory C 23 H 21 FN 4 O 4 (436.44) Mass spectrum: [M+H] + =437 EXAMPLE 9 Pyrimidine-5-carboxylic acid{1-[4-(4-carbamoyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 9a) 4-(4-formyl-phenoxy)-benzamide 3.1 g (23 mmol) of 4-hydroxybenzamide and 2.8 g (23 mmol) of 4-fluorobenzaldehyde were dissolved in DMSO, combined with 4.4 g (32 mmol) of K 2 CO 3 and stirred overnight at 140° C., filtered through basic Alox, washed with DMF, concentrated by rotary evaporation and purified by chromatography (silica gel column, dichloromethane with a gradient of 10-20% methanol). As there was still some DMF present, the mixture was triturated with water, suction filtered and dried Yield: 57% of theory C 14 H 11 NO 3 (241.25) Mass spectrum (EI):M +. =241 9b) 4-(4-aminomethyl-phenoxy)-benzamide Analogously to Example (7b) 4-(4-formyl-phenoxy)-benzamide was used as starting material. C 14 H 14 N 2 O 2 (242.28) Mass spectrum: [M−NH 2 ] + =226 9c) pyrimidine-5-carboxylic acid-{1-[4-(4-carbamoyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide Analogously to Example (7c) the title compound was prepared starting from 4-(4-aminomethyl-phenoxy)-benzamide. Yield: 69% of theory C 23 H 21 N 5 O 4 (431.54) Mass spectrum: [M+H] + =432 EXAMPLE 10 Pyrimidine-5-carboxylic acid[1-(2,6-dimethyl-4-phenoxy-benzylcarbamoyl)-cyclopropyl]-amide 10a) 2,6-dimethyl-4-phenoxy-benzaldehyde 2.3 g (25 mmol) of phenol and 3.8 g (25 mmol) of 2,6-dimethyl-4-fluorobenzaldehyde were dissolved in 60 ml DMA, combined with 4.8 g (35 mmol) of K 2 CO 3 and stirred at 150° C. for 5 min in a microwave (OEM Discoverer), filtered through basic Alox, washed with DMF and concentrated by rotary evaporation. Taken up in a mixture of acetonitrile/water. The substance crystallised, was filtered off and dried. Yield: 83% of theory C 15 H 14 O 2 (226.28) Mass spectrum: [M+H] + =227 10b) 2,6-dimethyl-4-phenoxy-benzylamine Analogously to Example (7b) 2,6-dimethyl-4-phenoxy-benzaldehyde was used as starting material. C 15 H 17 NO (227.31) Mass spectrum: [M−NH 2 ] + =211 10c) pyrimidine-5-carboxylic acid[1-(2,6-dimethyl-4-phenoxy-benzylcarbamoyl)-cyclopropyl]-amide Analogously to Example (7c) the title compound was prepared starting from 2,6-dimethyl-4-phenoxy-benzylamine. Yield: 53% of theory C 24 H 24 N 4 O 3 (416.48) Mass spectrum: [M+H] + =417 EXAMPLE 14 Pyrimidine-5-carboxylic acid(1-{4-[3-(pyrrolidine-1-carbonyl)-phenoxy]-benzylcarbamoyl}-cyclopropyl)-amide 14a) 3-(4-formyl-phenoxy)-benzoic acid 5.3 g (35 mmol) of methyl 3-hydroxy-benzoate and 4.3 g (35 mmol) of 4-fluorobenzaldehyde were dissolved in DMSO and 5.8 g (42 mmol) of K 2 CO 3 were added and tm stirred for 6 h at 80° C. Then it was filtered through basic Alox with Celite, concentrated by rotary evaporation and purified by chromatography (silica gel column, cyclohexane with gradient of 5-30% ethyl acetate). This was then combined with 50 ml of methanol and 24 ml of 2M NaOH, the mixture was stirred for 2 hours at ambient temperature and the methanol was eliminated. The residue was diluted with water and combined with 44 ml of 1M hydrochloric acid, during which time the product was precipitated. Washed with water and dried. Yield: 63% of theory C 14 H 10 O 4 (242.23) Mass spectrum: [M−H] − =241 14b) 4-[3-(pyrrolidine-1-carbonyl)-phenoxy]-benzaldehyde 1 g (4.1 mmol) of 3-(4-formyl-phenoxy)-benzoic acid were dissolved in 25 ml DMF and combined with 0.86 ml (4.95 mmol) of DIPEA and 1.32 g (4.1 mmol) of TBTU, stirred for 5 min at ambient temperature and then 0.29 g (4.1 mmol) of pyrrolidine were added. The mixture was stirred at ambient temperature, filtered through basic Alox, concentrated by rotary evaporation and purified by chromatography (silica gel column, dichloromethane with gradient of 0-10% methanol). Yield: 41% of theory. C 18 H 17 NO 3 (295.34) Mass spectrum: [M+H] + =296 14c) [3-(4-aminomethyl-phenoxy)-phenyl]-pyrrolidin-1-yl-methanone Analogously to Example (9b) 4-[3-(pyrrolidine-1-carbonyl)-phenoxy]-benzaldehyde was used as starting material. C 18 H 20 N 2 O 2 (296.37) Mass spectrum: [M−NH 2 ] + =280 14d) pyrimidine-5-carboxylic acid(1-{4-[3-(pyrrolidine-1-carbonyl)-phenoxy]-benzylcarbamoyl}-cyclopropyl)-amide Analogously to Example (7c) the title compound was prepared starting from [3-(4-aminomethyl-phenoxy)-phenyl]-pyrrolidin-1-yl-methanone. Yield: 77% of theory C 27 H 27 N 5 O 4 (485.54) Mass spectrum: [M+H] + =486 EXAMPLE 39 Pyrimidine-5-carboxylic acid-(1-{1-[4-(4-methoxy-phenoxy)-phenyl]-ethylcarbamoyl}-cyclopropyl)-amide 39a) 1-[4-(4-methoxy-phenoxy)-phenyl]-ethanone 138 mg (1 mmol) of 4-fluoroacetophenone were taken and 124 mg (1 mmol) of 4-methoxyphenol were dissolved in DMSO and added thereto, then 200 mg (1.45 mmol) of K 2 CO 3 were added and the mixture was stirred for 8 h at 80° C., then for 6 h at 100° C., then for 3 h at 120° C. and for 3 h at 140° C. The reaction mixture was filtered through basic Alox, washed with DMF/methanol=9/1 and concentrated by rotary evaporation. The substance was purified by reversed-phase chromatography. Yield: 32% of theory C 15 H 14 O 3 (242.27) Mass spectrum: [M+H] + =243 39b) 1-[4-(4-methoxy-phenoxy)-phenyl]-ethylamine 78 mg (0.32 mmol) of 1-[4-(4-methoxy-phenoxy)-phenyl]-ethanone were dissolved in 10 ml of 7M methanolic ammonia and combined with 50 mg of Raney nickel. The mixture was shaken for 6 h at 50° C. and 3 bar hydrogen pressure. Raney nickel was added twice more and hydrogenation was continued for 2 h and 6 h under the same conditions. The catalyst was removed by suction filtering and the residue was evaporated down. Yield: 73% of theory C 15 H 17 NO 2 (243.31) Mass spectrum: [M−NH 2 ] + =227 39c) pyrimidine-5-carboxylic acid-(1-{1-[4-(4-methoxy-phenoxy)-phenyl]-ethylcarbamoyl}-cyclopropyl)-amide Analogously to Example (7c) the title compound was prepared starting from 1-[4-(4-methoxy-phenoxy)-phenyl]-ethylamine. Yield: 32% of theory C 24 H 24 N 4 O 4 (432.48) Mass spectrum: [M+H] + =433 EXAMPLE 40 Pyrimidine-5-carboxylic acid-{1-[4-(2-chloro-phenoxy)-2-fluoro-benzylcarbamoyl]-cyclopropyl}-amide 40a) 4-(2-chlorophenoxy)-2-fluorobenzaldehyde 142 mg (1 mmol) of 2,4-difluorobenzaldehyde were dissolved in 5 ml DMSO and taken and combined with 200 mg (1.45 mmol) of K 2 CO 3 . 128 mg (1 mmol) of 2-chlorophenol were dissolved in 10 ml DMSO and added and stirred for 2 days at ambient temperature. The reaction mixture was filtered through basic Alox, washed with DMF and concentrated by rotary evaporation. The substance was purified by reversed-phase chromatography. Yield: 48% of theory. C 13 H 8 ClFO 2 (250.66) Mass spectrum: [M+H] + =251/253 40b) 4-(2-chlorophenoxy)-2-fluorobenzylamine 148 mg (0.59 mmol) of 4-(2-chlorophenoxy)-2-fluorobenzaldehyde were dissolved in 10 ml of 7M methanolic ammonia and 50 mg Raney nickel were added. The mixture was shaken for 4 h at 35° C. and 3 bar hydrogen pressure. The catalyst was removed by suction filtering, the residue was evaporated down and purified by reversed-phase chromatography. Yield: 43% of theory C 13 H 11 ClFNO (251.69) Mass spectrum: [M+H] + =252/254 40c) pyrimidine-5-carboxylic acid-{1-[4-(2-chloro-phenoxy)-2-fluoro-benzylcarbamoyl]-cyclopropyl}-amide Analogously to Example (7c) the title compound was prepared starting from 4-(2-chlorophenoxy)-2-fluorobenzylamine. Yield: 67% of theory C 22 H 18 ClFN 4 O 3 (440.86) Mass spectrum: [M+H] + =441/443 EXAMPLE 43 Pyrimidine-5-carboxylic acid-{1-[2-fluoro-4-(4-methoxy-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 43a) 2-fluoro-4-(4-methoxy-phenoxy)-benzaldehyde Analogously to Example (40a) 2,4-difluorobenzaldehyde and 4-methoxyphenol were used as starting material. Yield: 47% of theory C 14 H 11 FO 3 (246.24) Mass spectrum: [M+H] + =247 43b) 2-fluoro-4-(4-methoxy-phenoxy)-benzylamine 180 mg (0.73 mmol) of 2-fluoro-4-(4-methoxy-phenoxy)-benzaldehyde were stirred with 180 μl (3 mmol) of hydroxylamine solution (50% in water) in 5 ml DMF at 100° C. for 1 h and then stirred overnight at ambient temperature. The mixture was evaporated down, dissolved in 10 ml of 7M methanolic ammonia and combined with 50 mg Raney nickel. It was then shaken for 4 h at ambient temperature and 3 bar hydrogen pressure. The catalyst was removed by suction filtering, the residue was evaporated down and purified by reversed-phase chromatography. Yield: 52% of theory C 14 H 14 FNO 2 (247.27) Mass spectrum: [M−NH 2 ] + =231 43c) pyrimidine-5-carboxylic acid-{1-[2-fluoro-4-(4-methoxy-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide Analogously to Example (7c) the title compound was prepared starting from 2-fluoro-4-(4-methoxy-phenoxy)-benzylamine. Yield: 64% of theory C 23 H 21 FN 4 O 4 (436.45) Mass spectrum: [M+H] + =437 EXAMPLE 44 Pyrimidine-5-carboxylic acid(1-{1-[4-(2-chloro-phenoxy)-2-fluoro-phenyl]-ethylcarbamoyl}-cyclopropyl)-amide 44a) 1-[4-(2-chloro-phenoxy)-2-fluoro-phenyl]-ethanone 156 mg (1 mmol) of 2,4-difluoracetophenone were dissolved in 5 ml DMSO, taken and combined with 200 mg (1.45 mmol) of K 2 CO 3 . 128 mg (1 mmol) of 2-chlorophenol were dissolved in 5 ml DMSO and added thereto and the mixture was stirred for 2 days at ambient temperature. The reaction mixture was filtered through basic Alox, washed with DMF and concentrated by rotary evaporation. The substance was purified by reversed-phase chromatography. Yield: 35% of theory C 14 H 10 ClFO 2 (264.69) Mass spectrum: [M+H] + =265/267 44b) 1-[4-(2-chloro-phenoxy)-2-fluoro-phenyl]-ethylamine Analogously to Example (43b) 1-[4-(2-chloro-phenoxy)-2-fluoro-phenyl]-ethanone was used as starting material. Yield: 49% of theory C 14 H 13 ClFNO (265.72) Mass spectrum: [M−NH 2 ] + =249/251 44c) pyrimidine-5-carboxylic acid(1-{1-[4-(2-chloro-phenoxy)-2-fluoro-phenyl]-ethylcarbamoyl}-cyclopropyl)-amide Analogously to Example (7c) the title compound was prepared starting from 1-[4-(2-chloro-phenoxy)-2-fluoro-phenyl]-ethylamine. Yield: 56% of theory C 23 H 20 ClFN 4 O 3 (454.89) Mass spectrum: [M+H] + =455/457 EXAMPLE 49 Pyrimidine-5-carboxylic acid-{1-[4-(2-isopropyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 49a) 4-(2-isopropyl-phenoxy)-benzylamine 27 mg (0.2 mmol) of 2-isopropyl-phenol were dissolved in 2 ml DMSO. Then 41.4 mg (0.3 mmol) of K 2 CO 3 and 1 ml of a 0.2 M solution of 4-fluoro-benzaldehyde in DMSO were added and the mixture was shaken overnight at 100° C. It was then filtered through basic Alox, washed with DMF and concentrated by rotary evaporation. The residue was dissolved in 2 ml of methanol and 7 ml of 7M methanolic ammonia were added, Ra—Ni was added and the mixture was shaken for 7 hours at 55° C. and 3.5 bar H 2 pressure. The catalyst was removed by suction filtering, washed with methanol and the solution was evaporated down in vacuo, dissolved in 2 ml DMF and purified by chromatography. Yield: 14% according to UV chromatography in the LCMS C 16 H 19 NO (241.34) Mass spectrum: [M−NH 2 ] + =225 49b) pyrimidine-5-carboxylic acid-{1-[4-(2-isopropyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide Analogously to Example (7c) the title compound was prepared from 1-[(pyrimidine-5-carbonyl)-amino]-cyclopropanecarboxylic acid and 4-(2-isopropyl-phenoxy)-benzylamine. Yield: 89% of theory C 25 H 26 N 4 O 3 (430.51) Mass spectrum: [M+H] + =431 EXAMPLE 74 Pyrimidine-5-carboxylic acid{1-[2-chloro-4-(2-chloro-phenoxy)-benzyl-carbamoyl]-cyclopropyl}-amide 74a) 2-chloro-4-(2-chloro-phenoxy)-benzonitrile A solution of 1.17 g (7.54 mmol) of 2-chloro-4-fluorobenzonitrile and 0.97 g (7.54 mmol) of 2-chlorophenol in 40 mL DMSO was combined with 3.2 g (23.16 mmol) of potassium carbonate and stirred overnight at 120° C. Then the mixture was evaporated to dryness in vacuo, the residue was mixed with water and extracted with ethyl acetate. The extracts were washed with water and saturated sodium chloride solution, dried and evaporated down. The crude product thus obtained was purified by column chromatography (silica gel, dichloromethane). Yield: 60% of theory C 13 H 7 Cl 2 NO (264.106) Mass spectrum: [M+NH 4 ] + =281/3/5 74b) 2-chloro-4-(2-chloro-phenoxy)-benzylamine 1.2 g (4.54 mmol) of 2-chloro-4-(2-chloro-phenoxy)-benzonitrile were dissolved in 30 mL methanol and 30 ml 7M methanolic ammonia were added, then 150 mg Raney nickel were added to the mixture. It was shaken at 50° C. under 50 psi hydrogen pressure. The catalyst was separated off by suction filtering and the filtrate was evaporated down. Yield: 98% of theory C 13 H 11 Cl 2 NO (268.14) Mass spectrum: [M+H] + =268/70/2 74c) Pyrimidine-5-carboxylic acid{1-[2-chloro-4-(2-chloro-phenoxy)-benzyl-carbamoyl]-cyclopropyl}-amide 85 mg (0.84 mmol) of triethylamine, 130 mg (0.40 mmol) of TBTU and 100 mg (0.37 mmol) of 2-chloro-4-(2-chloro-phenoxy)-benzylamine were added to a solution of 80 mg (0.38 mmol) of 1-[(pyrimidin-5-carbonyl)-amino]-cyclopropanecarboxylic acid (from 1 b) in 30 mL tetrahydrofuran and 5 mL DMF and the mixture was stirred overnight at ambient temperature. Then the mixture was evaporated to dryness and the residue was combined with 2 M potassium carbonate solution. It was extracted with ethyl acetate and the organic phase was washed with water and saturated sodium chloride solution, dried and evaporated down. The crude product thus obtained was purified by reversed-phase chromatography. The fractions were evaporated down to the aqueous phase, made basic with ammonia and extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried and evaporated down. The residue was evaporated out with ether and dried. Yield: 29% of theory C 22 H 18 Cl 2 N 4 O 3 (457.31) Mass spectrum: [M+H] + =457/9/61 R f =0.7 thin layer chromatography (silica gel, dichloromethane+methanol 9:1) EXAMPLE 75 Pyrimidine-5-carboxylic acid(1-{1-[2-chloro-4-(2-chloro-phenoxy)-phenyl]-ethylcarbamoyl}-cyclopropyl)-amide 75a) 1-[2-chloro-4-(2-chloro-phenoxy)-phenyl]-ethanone Obtained analogously to Example 74a) starting from 2-chloro-4-fluoracetophenone and 2-chlorophenol. Yield: 77% of theory C 14 H 10 Cl 2 O 2 (281.13) Mass spectrum: [M+H] + =281/3/5 75b) 1-[2-chloro-4-(2-chloro-phenoxy)-phenyl]-ethanone-oxime A mixture of 2.4 g (8.54 mmol) of 1-[2-chloro-4-(2-chloro-phenoxy)-phenyl]-ethanone and 0.76 mL hydroxylamine solution (50% in water) in 60 mL ethanol was refluxed for 24 hours. Then the mixture was evaporated to dryness and the residue was purified by chromatography (silica gel column, methylene chloride). Yield: 73% of theory C 14 H 11 Cl 2 NO 2 (296.15) Mass spectrum: [M+H] + =296/8/300 75c) 1-[2-chloro-4-(2-chloro-phenoxy)-phenyl]-ethylamine 1.8 g (6.08 mmol) of 1-[2-chloro-4-(2-chloro-phenoxy)-phenyl]-ethanone-oxime was dissolved in 50 mL methanol and 50 mL 7M methanolic ammonia were added, followed by 400 mg Raney nickel. The mixture was shaken at RT and 50 psi hydrogen pressure. The catalyst was suction filtered and the filtrate was evaporated down. The residue was purified by chromatography (silica gel column, dichloromethane:methanol=50:1 to 9:1) Yield: 42% of theory C 14 H 13 Cl 2 NO (282.16) Mass spectrum: [M+H] + =282/4/6 75d) Pyrimidine-5-carboxylic acid(1-{1-[2-chloro-4-(2-chloro-phenoxy)-phenyl]-ethylcarbamoyl}-cyclopropyl)-amide Analogously to Example (74c) the title compound was prepared starting from 1-[2-chloro-4-(2-chloro-phenoxy)-phenyl]-ethylamine. Yield: 35% of theory C 23 H 20 Cl 2 N 4 O 3 (471.34) Mass spectrum: [M+H] + =471/473/475 R f =0.15 thin layer chromatography (silica gel, dichloromethane+methanol 19:1) EXAMPLE 76 Pyrimidine-5-carboxylic acid{1-[2-chloro-4-(2-chloro-4-hydroxy-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 76a) 2-chloro-4-(2-chloro-4-methoxy-phenoxy)-benzonitrile A solution of 3.0 g (19.28 mmol) of 2-chloro-4-fluorobenzonitrile and 3.06 g (19.28 mmol) of 2-chloro-4-methoxyphenol in 77 mL DMSO was combined with 5.32 g (38.57 mmol) of potassium carbonate and stirred for 2 h at 120° C. Then the mixture was evaporated to dryness in vacuo, the residue was taken up in dichloromethane and washed once with semisaturated potassium carbonate solution and twice with water. The organic phase was dried on sodium sulphate and evaporated down. Yield: 100% of theory C 14 H 9 Cl 2 NO 2 (294.13) Mass spectrum: [M−H] − =292/4/6 76b) 2-chloro-4-(2-chloro-4-hydroxy-phenoxy)-benzonitrile 0.5 g (1.7 mmol) of 2-chloro-4-(2-chloro-4-methoxy-phenoxy)-benzonitrile and 2.21 mL (2.21 mmol) of boron tribromide 1M in dichloromethane were stirred in 5.5 mL dichloromethane for 5 days at RT. The mixture was carefully combined with methanol and then water and dichloromethane were added. The phases were separated and the aqueous phase was extracted twice more with dichloromethane. The organic phase was dried on sodium sulphate and evaporated down. Yield: 100% of theory C 13 H 7 Cl 2 NO 2 (280.11) Mass spectrum: [M−H] − =278/80/2 76c) 4-(4-aminomethyl-3-chloro-phenoxy)-3-chloro-phenol-trifluoroacetic acid salt 74 mg (1.96 mmol) of lithium aluminium hydride were taken and at 0° C. 3 mL of THF were added dropwise. Then 498 mg (1.78 mmol) of 2-chloro-4-(2-chloro-4-hydroxy-phenoxy)-benzonitrile in 3 mL THF was slowly added dropwise at 0° C. The reaction mixture was stirred overnight at RT, then combined with 2M sodium hydroxide solution at 0° C. and filtered through Celite. The mixture was washed with THF and the filtrate was dried on sodium sulphate and evaporated down. The residue was purified by chromatography (reversed phase). Yield: 21% of theory C 13 H 11 Cl 2 NO 2 (284.14) Mass spectrum: [M−NH 2 ] + =267/9/71 76d) Pyrimidine-5-carboxylic acid{1-[2-chloro-4-(2-chloro-4-hydroxy-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 269 μl (1.93 mmol) of triethylamine and 166 mg (0.52 mmol) of TBTU were added to a solution of 100 mg (0.48 mmol) of 1-[(pyrimidin-5-carbonyl)-amino]-cyclopropanecarboxylic acid (from 1b) in 5 mL DMF and the mixture was stirred for 10 min at RT. Then 147 mg (0.37 mmol) of 4-(4-aminomethyl-3-chloro-phenoxy)-3-chloro-phenol-trifluoroacetic acid salt dissolved in 30 mL THF was added. The reaction mixture was stirred for 2 h at RT and evaporated to dryness. The residue was purified by chromatography (reversed phase). Yield: 43% of theory C 22 H 18 Cl 2 N 4 O 4 (473.31) Mass spectrum: [M+H] + =473/5/7 EXAMPLE 77 1-(2,2,2-trifluoro-acetylamin)-cyclopropanecarboxylic acid 4-(2-chloro-4-methoxy-phenoxy)-benzylamide 77a) 1-(2,2,2-trifluoro-acetylamin)-cyclopropanecarboxylic acid 4-(2-chloro-4-methoxyphenoxy)-benzylamide 150 mg (0.43 mmol) of 1-amino-cyclopropanecarboxylic acid 4-(2-chloro-4-methoxy-phenoxy)-benzylamide was dissolved in 15 mL dichloromethane, and 90 μL (0.65 mmol) of triethylamine and 72 μL (0.52 mmol) of trifluoroacetic acid were added. The reaction mixture was stirred for 2 h at RT and then mixed with water and evaporated down. The residue was dissolved in DMF and purified by chromatography (reversed phase). Yield: 29% of theory C 20 H 18 ClF 3 N 2 O 4 (442.82) Mass spectrum: [M−H] − =441/3 EXAMPLE 78 Pyrimidine-5-carboxylic acid{1-[4-(4-bromo-2-chloro-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 78a) 4-(4-bromo-2-chloro-phenoxy)-benzaldehyde A solution of 50 mg (0.40 mmol) of 4-fluorobenzaldehyde and 83.6 mg (0.40 mmol) of 4-bromo-2-chlorophenol in 2 mL DMSO was combined with 80 mg (0.58 mmol) of potassium carbonate and stirred overnight at 120° C. The reaction mixture was filtered through Alox B, washed with dichloromethane and evaporated down. The residue was purified by chromatography (reversed phase). Yield: 16% of theory C 13 H 8 BrClO 2 (311.56) Mass spectrum: [M+H] + =311/3/5 78b) 4-(4-bromo-2-chloro-phenoxy)-benzaldehyde-oxime 20 mg (0.06 mmol) of 4-(4-bromo-2-chloro-phenoxy)-benzaldehyde were stirred with 20 μL (0.33 mmol) of hydroxylamine solution (50% in water) in 2 mL f DMF at 80° C. for 1 h. The reaction mixture was purified by chromatography (reversed phase). Yield: 86% of theory C 13 H 9 BrClNO 2 (326.57) Mass spectrum: [M+H] + =326/8/30 78c) 4-(4-bromo-2-chloro-phenoxy)-benzylamine 18 mg (0.06 mmol) of 4-(4-bromo-2-chloro-phenoxy)-benzaldehyde-oxime was dissolved in 2 mL methanol, then 37 mg (0.15 mmol) of nickel(II)chloride hexahydrate and 21 mg (0.56 mmol) of sodium borohydride were slowly added. The reaction mixture was stirred overnight at RT and then purified by chromatography (reversed phase). Yield: 46% of theory C 13 H 11 BrClNO (312.59) Mass spectrum: [M+H] + =295/7/9 78d) Pyrimidine-5-carboxylic acid{1-[4-(4-bromo-2-chloro-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 7 μL (0.05 mmol) of triethylamine and 8.4 mg (0.03 mmol) of TBTU were added to a solution of 5.4 mg (0.03 mmol) of 1-[(pyrimidin-5-carbonyl)-amino]-cyclo-propanecarboxylic acid (from 1b) in 1 mL DMF and stirred for 5 min at RT. Then 8 mg (0.03 mmol) of 4-(4-bromo-2-chloro-phenoxy)-benzylamine was added and the mixture was stirred overnight at ambient temperature. The reaction mixture was purified by chromatography (reversed phase). Yield: 84% of theory C 22 H 18 BrClN 4 O 3 (501.76) Mass spectrum: [M−H] − =499/501/3 EXAMPLE 79 Pyrimidine-5-carboxylic acid{1-[4-(4-bromo-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 79a) 4-(4-bromo-2-trifluoromethyl-phenoxy)-benzaldehyde Prepared analogously to Example 78a) starting from 4-fluorobenzaldehyde and 4-bromo-2-(trifluoromethyl)-benzenol. Yield: 30% of theory C 14 H 8 BrF3O 2 (345.11) Mass spectrum: [M+H] + =345/7 79b) 4-(4-bromo-2-trifluoromethyl-phenoxy)-benzaldehyde-oxime Prepared analogously to 78b) starting from 4-(4-bromo-2-trifluoromethyl-phenoxy)-benzaldehyde, it was further reacted directly without chromatographic purification. Yield: 100% of theory C 14 H 9 BrF 3 NO 2 (360.13) Mass spectrum: [M+H] + =360/2 79c) 4-(4-bromo-2-trifluoromethyl-phenoxy)-benzylamine-trifluoroacetic acid salt Prepared analogously to 78c) starting from 4-(4-bromo-2-trifluoromethyl-phenoxy)-benzaldehyde-oximebut with a reaction time of only 10 min. Yield: 52% of theory C 14 H 11 BrF 3 NO (346.15) Mass spectrum: [M+H] + =346/8 79d) Pyrimidine-5-carboxylic acid{1-[4-(4-bromo-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide Analogously to Example (78d) the title compound was prepared starting from 4-(4-bromo-2-trifluoromethyl-phenoxy)-benzylamine-trifluoroacetic acid salt. Yield: 80% of theory C 23 H 18 BrF 3 N 4 O 3 (535.32) Mass spectrum: [M+H] + =535/7 EXAMPLE 81 Pyrimidine-5-carboxylic acid(1-{1-[4-(4-difluoromethoxy-phenoxy)-phenyl]-ethylcarbamoyl}-cyclopropyl)-amide 81 a) 1-[4-(4-difluoromethoxy-phenoxy)-phenyl]-ethanone A solution of 666 μL (5.52 mmol) of 4-fluoroacetophenone and 883 mg (5.52 mmol) of 4-(difluoromethoxy)phenol in 10 mL DMSO was combined with 1.91 g (13.78 mmol) of potassium carbonate and stirred overnight at 100° C. The reaction mixture was poured onto 250 mL semisaturated sodium chloride solution and extracted twice with tert-butylmethylether. The organic phase was dried and evaporated down. The residue was purified by chromatography (silica gel, petroleum ether/ethyl acetate). Yield: 89% of theory C 15 H 12 F 2 O 3 (278.25) Mass spectrum: [M+H] + =279 81b) 1-[4-(4-difluoromethoxy-phenoxy)-phenyl]-ethanone-oxime A mixture of 1.37 g (4.92 mmol) of 1-[4-(4-difluoromethoxy-phenoxy)-phenyl]-ethanone and 1.16 mL hydroxylamine solution (50% in water) in 5 mL ethanol was refluxed for 3 hours. Then the mixture was concentrated and evaporated down several times with ethanol, and the residue was purified by chromatography (silica gel column, petroleum ether/ethyl acetate). Yield: 94% of theory C 15 H 13 F 2 NO 3 (293.27) Mass spectrum: [M+H] + =294 81c) 1-[4-(4-difluoromethoxy-phenoxy)-phenyl]-ethylamine 1.35 g (4.60 mmol) of 1-[4-(4-difluoromethoxy-phenoxy)-phenyl]-ethanone-oxime were dissolved in 50 ml of 7M methanolic ammonia, then combined with 100 mg Raney nickel. The mixture was shaken overnight at RT and 50 psi hydrogen pressure. The catalyst was removed by suction filtering and the filtrate was evaporated down. Yield: 99% of theory C 15 H 15 F 2 NO 2 (279.28) Mass spectrum: [M−NH 2 ] + =263 81d) Pyrimidine-5-carboxylic acid(1-{1-[4-(4-difluoromethoxy-phenoxy)-phenyl]-ethylcarbamoyl}-cyclopropyl)-amide 376 μL (2.70 mmol) of triethylamine and 0.52 g (1.62 mmol) of TBTU were added to a solution of 0.28 g (1.35 mmol) of 1-[(pyrimidin-5-carbonyl)-amino]-cyclo-propanecarboxylic acid (from 1b) in 5 mL DMF and the mixture was stirred for 5 min at RT. Then 0.42 g (1.50 mmol) of 1-[4-(4-difluoromethoxy-phenoxy)-phenyl]-ethylamine was added and the mixture was stirred for 30 min at ambient temperature. The reaction mixture was purified by chromatography (reversed phase). The acetonitrile was distilled off, the aqueous phase was made basic with ammonia and extracted with dichloromethane. The organic phase was dried and evaporated down. Yield: 66% of theory C 24 H 22 F 2 N 4 O 4 (468.45) Mass spectrum: [M−H] − =467 EXAMPLE 82 Pyrimidine-5-carboxylic acid(1-{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-phenyl]-ethylcarbamoyl}-cyclopropyl)-amide 82a) 1-benzyloxy-4-methoxy-2-trifluoromethyl-benzene 18 g (166.67 mmol) of benzylalcohol was slowly added to a solution of 6.7 g (167.50 mmol) of sodium hydride in 148 mL NMP. The reaction mixture was stirred for 30 min at RT, then a solution of 27 g (139.09 mmol) of 1-fluoro-4-methoxy-2-trifluoromethyl-benzene in 515 mL NMP was added, and this was stirred for 30 min at RT and for 2 h at 100° C. After cooling to RT the mixture was diluted with water and extracted with ethyl acetate, the organic phase was washed with saturated sodium chloride solution, dried on sodium sulphate and evaporated down. The residue was purified by chromatography (silica gel, petroleum ether/ethyl acetate). Yield: 76% of theory C 15 H 13 F 3 O 2 (282.26) Mass spectrum: [M+]=282 R f =0.4 thin layer chromatography (silica gel, ethyl acetate/petroleum ether 7:93) 82b) 4-methoxy-2-trifluoromethyl-phenol 30 g (106.28 mmol) of 1-benzyloxy-4-methoxy-2-trifluoromethyl-benzene were dissolved in 60 mL ethyl acetate and then combined with 3 g palladium/C 10%. The mixture was shaken at RT and 50 psi hydrogen pressure for 4 h. The reaction mixture was suction filtered through Celite and the filtrate was evaporated down. The residue was purified by chromatography (silica gel, petroleum ether/ethyl acetate). Yield: 97% of theory C 8 H 7 F 3 O 2 (192.14) Mass spectrum: [M−H] − =191 R f =0.2 thin layer chromatography (silica gel, ethyl acetate/petroleum ether 1:10) 82c) 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzonitrile A solution of 4 g (20.82 mmol) of 4-methoxy-2-trifluoromethyl-phenol and 2.52 g (20.82 mmol) of 4-fluorobenzonitrile in 60 mL DMSO was combined with 5.75 g (41.64 mmol) of potassium carbonate and stirred for 3 h at 120° C. The reaction mixture was diluted with water, and extracted three times with dichloromethane. The organic phase was washed twice with water, dried on sodium sulphate and evaporated down. The residue was purified by chromatography (reversed phase). Yield: 52% of theory C 18 H 10 F 3 NO 2 (293.24) Mass spectrum: [M−H] − =292 82d) 1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-phenyl]-ethanone 4.87 mL (6.82 mmol) of methylmagnesium bromide (1.4 M in THF) was placed under a nitrogen atmosphere and cooled to −20° C., then 0.5 g (1.71 mmol) of 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzonitrile in 2.5 mL diethyl ether was added dropwise. After this addition the mixture was stirred for a further 15 min at −20° C. and then allowed to come up to RT. The reaction mixture was slowly added to an ice/ammonium chloride refrigerant mixture and then extracted with diethyl ether. The organic phase was dried and evaporated down. The residue was purified by chromatography (silica gel, petroleum ether/acetic acid ethyl ester). Yield: 62% of theory C 16 H 13 F 3 O 3 (310.27) Mass spectrum: [M+H] + =311 82e) 1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-phenyl]-ethanone-oxime Prepared analogously to Example 81b) starting from 1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-phenyl]-ethanone. Yield: 95% of theory C 16 H 14 F 3 NO 3 (325.28) Mass spectrum: [M+H] + =326 82f) 1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-phenyl]-ethylamine Prepared analogously to Example 2c) starting from 1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-phenyl]-ethanone-oxime. Yield: 100% of theory C 16 H 16 F 3 NO 2 (311.30) Mass spectrum (EI): [M*+]=311 82g) Pyrimidine-5-carboxylic acid(1-{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-phenyl]-ethylcarbamoyl}-cyclopropyl)-amide Prepared analogously to Example 76d) starting from 1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-phenyl]-ethylamine. Yield: 53% of theory C 25 H 23 F 3 N 4 O 4 (500.47) Mass spectrum: [M+H] + =501 EXAMPLE 83 N-{1-[4-(2-chloro-4-methoxy-phenoxy)-benzylcarbamoyl]-cyclopropyl}-5-trifluoromethyl-nicotinamide 83a) N-{1-[4-(2-chloro-4-methoxy-phenoxy)-benzylcarbamoyl]-cyclopropyl}-5-trifluoromethyl-nicotinamide 102 μL (0.73 mmol) of triethylamine and 117 mg (0.36 mmol) of TBTU were added to a solution of 73.7 mg (0.37 mmol) of 1-tert-butoxycarbonylamino-cyclopropanecarboxylic acid in 6 mL DMF and the mixture was stirred for 5 min at RT. Then 96.6 mg (0.37 mmol) of 4-(2-chloro-4-methoxy-phenoxy)-benzylamine was added and the mixture was stirred overnight at ambient temperature. The reaction mixture was filtered through Alox B, washed with DMF and the filtrate was evaporated down. 10 ml of dichloromethane/trifluoroacetic acid=1/1 were added to the residue and this was shaken for 1 h at RT. The reaction mixture was evaporated down and the residue was purified by chromatography (reversed phase). The corresponding fractions were freeze-dried. 35 mg (0.18 mmol) of 5-(trifluoromethyl)nicotinic acid was dissolved in 2 ml DMF and combined with 52 μL (0.37 mmol) of triethylamine and 59 mg (0.18 mmol) of TBTU and stirred for 10 min at RT. Then the freeze-dried 1-amino-cyclopropanecarboxylic acid-4-(2-chloro-4-methoxy-phenoxy)-benzylamide was added and the mixture was stirred overnight at RT. The reaction mixture was purified directly by chromatography (reversed phase). Yield: 21% of theory C 25 H 21 ClF 3 N 3 O 4 (519.90) Mass spectrum: [M+H] + =520 EXAMPLE 84 Pyrimidine-5-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 84a) 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylamine 2.53 g (8.63 mmol) of 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzonitrile (from 82c) were dissolved in 100 ml 7M methanolic ammonia, then combined with 250 mg Raney nickel. The mixture was shaken at RT and 50 psi hydrogen pressure for 3 h. The catalyst was removed by suction filtering and the filtrate was evaporated down. Yield: 90% of theory C 15 H 14 F 3 NO 2 (297.27) Mass spectrum: [M−NH2] + =281 84b) Pyrimidine-5-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide Prepared analogously to Example 78d) starting from 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylamine. C 24 H 21 F 3 N 4 O 4 (486.44) Mass spectrum: [M+H] + =487 EXAMPLE 85 1-(4-dimethylamino-butyrylamino)-cyclopropanecarboxylic acid 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylamide 85a) 1-amino-cyclopropanecarboxylic acid 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylamide 540 μL (3.85 mmol) of triethylamine and 864 mg (2.69 mmol) of TBTU were added to a solution of 541.5 mg (2.69 mmol) of 1-tert-butoxycarbonylamino-cyclopropanecarboxylic acid in 45 mL DMF and the mixture was stirred for 5 min at RT. Then 800 mg (2.69 mmol) of 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylamine (from 84a) was added and the mixture was stirred for 2 h at ambient temperature. The reaction mixture was filtered through Alox B, washed with DMF/MeOH=9/1 and the filtrate was evaporated down. 20 ml dichloromethane/trifluoroacetic acid/water=50/45/5 were added to the residue and the mixture was stirred for 1 h at RT. The reaction mixture was evaporated down, the residue was dissolved in dichloromethane and extracted with 10 mL of 1 M sodium hydroxide solution. The dichloromethane phase was separated off and evaporated down. Yield: 79% of theory C 19 H 19 F 3 N 2 O 3 (380.36) Mass spectrum: [M+H] + =381 85b) 1-(4-dimethylamino-butyrylamino)-cyclopropanecarboxylic acid 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylamide 1.44 mg (11 μMol) 4-dimethylamino-butyric acid was dissolved in 100 μL DMF, 3.5 μL (24.95 μMol) triethylamine and 3.37 mg (10.5 μMol) TBTU in 100 μL DMF were added and the mixture was stirred for 10 min at RT. Then 3.80 mg (10 μMol) 1-amino-cyclopropanecarboxylic acid 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylamide in 100 μL DMF was added and the mixture was shaken for 3 days at ambient temperature. Filtered through Alox B, washed with DMF/MeOH=9/1 and the filtrate was evaporated down. Yield: 73% of theory C 25 H 30 F 3 N 3 (493.53) Mass spectrum: [M+H] + =494 EXAMPLE 100 1-(2-cyano-acetylamino)-cyclopropanecarboxylic acid 4-(4-methoxy-2-tri-fluoromethyl-phenoxy)-benzylamide 100a) 1-(2-cyano-acetylamino)-cyclopropanecarboxylic acid 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylamide Prepared analogously to Example 85b) starting from cyanoacetic acid and 1-amino-cyclopropanecarboxylic acid 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylamide (from 85a). In addition, the residue was finally purified by chromatography (reversed phase). Yield: 25% of theory C 22 H 20 F 3 N 3 (447.42) Mass spectrum: [M+H] + =448 EXAMPLE 106 3-methyl-isoxazole-4-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 106a) 3-methyl-isoxazole-4-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 37 μL (0.26 mmol) of triethylamine and 84.4 mg (0.26 mmol) of TBTU were added to a solution of 33.4 mg (0.26 mmol) of 3-methylisoxazole-4-carboxylic acid in 5 mL DMF and the mixture was stirred for 10 min at RT. Then 100 mg (0.26 mmol) of 1-amino-cyclopropanecarboxylic acid 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylamide (from 85a) was added and the mixture was stirred for 4 h at ambient temperature and overnight at 40° C. The reaction mixture was purified by chromatography (reversed phase). Yield: 12% of theory C 24 H 22 F 3 N 3 O 5 (489.44) Mass spectrum: [M+H] + =490 EXAMPLE 107 3-methoxy-isoxazole-5-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 107a) 3-methoxy-isoxazole-5-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide Prepared analogously to Example 106a) starting from 3-methoxy-isoxazole-5-carboxylic acid. The reaction time was 4 h at RT. Yield: 25% of theory C 24 H 22 F 3 N 3 O 6 (505.44) Mass spectrum: [M+H] + =506 EXAMPLE 108 5-methyl-isoxazole-4-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}amide 108a) 5-methyl-isoxazole-4-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}amide Prepared analogously to Example 106a) starting from 3-methyl-isoxazole-4-carboxylic acid. The reaction was carried out overnight at RT. Yield: 45% of theory C 24 H 22 F 3 N 3 O 5 (489.44) Mass spectrum: [M+H] + =490 EXAMPLE 109 N-{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-malonic acid monoamide monoethylester 109a) N-{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-malonic acid monoamide monoethylester 87 μL (0.50 mmol) of DIPEA and 80.9 mg (0.25 mmol) of TBTU were added to a solution of 33.27 mg (0.25 mmol) of monoethylmalonate in 100 μL DMF and the mixture was stirred for 5 min at RT. Then 83 mg (0.17 mmol) of 1-amino-cyclopropanecarboxylic acid 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylamide-trifluoroacetic acid salt (from 85a) was added and the mixture was stirred for 1.5 h at ambient temperature. The reaction mixture was purified by chromatography (reversed phase). Yield: 76% of theory C 24 H 25 F 3 N 2 O 6 (494.46) Mass spectrum: [M+H] + =495 EXAMPLE 113 2-methoxy-N-{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-nicotinamide 113a) 2-methoxy-N-{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-nicotinamide Prepared analogously to Example 109a) starting from 2-methoxynicotinic acid. The reaction time was 24 h at RT. Yield: 61% of theory C 26 H 24 F 3 N 3 O 5 (515.48) Mass spectrum: [M+H] + =516 EXAMPLE 114 N-{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-malonic acid monoamide 114a) N-{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}malonic acid monoamide 33 mg (0.067 mmol) of N-{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-malonic acid monoamide monoethylester (from 109a) was stirred for 1 h at RT together with 1 mL sodium hydroxide solution 1M in 20 mL THF. The reaction mixture was evaporated down and the residue was purified by chromatography (reversed phase). Yield: 26% of theory C 22 H 21 F 3 N 2 O 6 (466.41) Mass spectrum: [M+H] + =467 EXAMPLE 116 6-methoxy-pyridine-2-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 116a) 6-methoxy-pyridine-2-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide Prepared analogously to Example 109a) starting from 6-methoxy-2-pyridincarboxylic acid. The reaction was carried out overnight at RT. Yield: 53% of theory C 26 H 24 F 3 N 3 O 5 (515.48) Mass spectrum: [M+H] + =516 EXAMPLE 118 6-hydroxy-pyridine-2-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 118a) 6-hydroxy-pyridine-2-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 74 μL (0.43 mmol) of DIPEA and 57.7 mg (0.18 mmol) of TBTU were added to a solution of 20 mg (0.14 mmol) of 6-hydroxypicolinic acid in 100 μL DMF and the mixture was stirred for 5 min at RT. Then 71 mg (0.14 mmol) of 1-amino-cyclopropanecarboxylic acid 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylamide-trifluoroacetic acid salt (from 84a) was added and the mixture was stirred for 3 days at ambient temperature. The reaction mixture was purified by chromatography (reversed phase). Yield: 52% of theory C 25 H 22 F 3 N 3 O 5 (501.46) Mass spectrum: [M+H] + =502 EXAMPLE 119 2-methoxy-N-{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-isonicotinamide 119a) 2-methoxy-N-{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-isonicotinamide Prepared analogously to Example 118a) from 2-methoxy-4-pyridinecarboxylic acid. The reaction time was 2 h at RT. Yield: 51% of theory C 26 H 24 F 3 N 3 O 5 (515.48) Mass spectrum: [M+H] + =516 EXAMPLE 120 2-fluoro-N-{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-isonicotinamide 120a) 2-fluoro-N-{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-isonicotinamide 68 μL (0.48 mmol) of TEA and 57 mg (0.19 mmol) of TBTU were added to a solution of 23 mg (0.16 mmol) of 6-fluoro-nicotinic acid in 2 mL DMF and the mixture was stirred for 5 min at RT. Then 80 mg (0.16 mmol) of 1-amino-cyclopropanecarboxylic acid 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylamide-trifluoroacetic acid salt (from 85a) was added and the mixture was stirred for 2 h at ambient temperature. A further 57 mg (0.19 mmol) of TBTU, 68 μL (0.48 mmol) of TEA and 23 mg (0.16 mmol) of 6-fluoro-nicotinic acid were added and the mixture was stirred overnight at RT. The reaction mixture was purified by chromatography (reversed phase). Yield: 33% of theory C 25 H 21 F 4 N 3 O 4 (503.46) Mass spectrum: [M+H] + =504 EXAMPLE 125 Oxazole-5-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 125a) oxazole-5-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 57.5 μL (0.41 mmol) of TEA and 48 mg (0.15 mmol) of TBTU were added to a solution of 15.4 mg (0.14 mmol) of oxazole-5-carboxylic acid in 1.5 mL DMF and the mixture was stirred for 5 min at RT. Then 67.5 mg (0.14 mmol) of 1-amino-cyclopropanecarboxylic acid 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylamide-trifluoroacetic acid salt (from 85a) were added and the mixture was stirred for 2 h at ambient temperature. The reaction mixture was purified by chromatography (reversed phase). Yield: 25% of theory C 23 H 20 F 3 N 3 O 5 (475.42) Mass spectrum: [M+H] + =476 EXAMPLE 129 6-methyl-pyridine-2-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 129a) 6-methyl-pyridine-2-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}amide 28 μL (0.20 mmol) of TEA and 118.8 mg (0.30 mmol) of HATU were added to a solution of 27.7 mg (0.20 mmol) of 6-methylpicolinic acid in 5 mL DMF and the mixture was stirred for 5 min at RT. Then 112 μL (0.81 mmol) of TEA and 100 mg (0.20 mmol) of 1-amino-cyclopropanecarboxylic acid 4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylamide-trifluoroacetic acid salt (from 85a) were added and the mixture was stirred overnight at RT. The reaction mixture was purified by chromatography (reversed phase). Yield: 80% of theory C 26 H 24 F 3 N 3 O 4 (499.48) Mass spectrum: [M+H] + =500 EXAMPLE 139 N-{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-succinic acid-monoamid A solution of 82 mg (0.166 mmol) of N-{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-succinic acid-monoamide-methylester (product from Example 132) and 2 mL sodium hydroxide solution (1 N) in 10 mL THF was stirred for two hours at ambient temperature, then neutralised with 0.1 N hydrochloric acid and evaporated down. The solid residue was stirred in approx. 3 mL dichloromethane, filtered off and evaporated down again. Yield: 98% of theory C 23 H 23 F 3 N 2 O 6 (480.43) Mass spectrum: [M+H] + =481 EXAMPLE 140 Pyrimidine-5-carboxylic acid{1-[4-(4-cyano-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide A solution of 100 mg (0.32 mmol) of pyrimidin-5-carboxylic acid[1-(4-hydroxy-benzylcarbamoyl)-cyclopropyl]-amide, 60.5 mg (0.32 mmol) of 4-fluoro-3-trifluoromethyl-benzonitrile and 110 mg (0.8 mmol) of potassium carbonate in 5 mL DMF was stirred for two hours at 110° C. After cooling the mixture was diluted with approx. 3 mL acetone, filtered and evaporated down. The crude product thus obtained was purified by column chromatography (reversed phase). Yield: 82% of theory C 24 H 18 F 3 N 6 O 3 (481.43) Mass spectrum: [M+H] + =481 EXAMPLE 148 2-methanesulphinyl-pyrimidine-5-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide 186 mg (1.08 mmol) of 3-chloroperbenzoic acid were added at approx. 5° C. to a solution of 575 mg (1.08 mmol) of 2-methylthio-pyrimidine-5-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide (product from Example 144) in 10 mL dichloromethane. Then the cooling was removed and the reaction mixture stirred for a further three hours at ambient temperature. Half the solution was evaporated down and the crude product thus obtained was purified by chromatography (reversed phase HPLC). Yield: 6% of theory C 25 H 23 F 3 N 4 O 5 S (548.54) Mass spectrum: [M+H] + =549 EXAMPLE 149 2-methanesulphonyl-pyrimidine-5-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide Half the crude product mixture from Example 148 was combined with a further 186 mg 3-chloroperbenzoic acid and stirred for two hours at ambient temperature. After the solution had been evaporated down the crude product thus obtained was purified by chromatography (reversed phase HPLC). Yield: 47% of theory C 25 H 23 F 3 N 4 O 6 S (564.54) Mass spectrum: [M+H] + =565 EXAMPLE 152 2-Cyano-pyrimidine-5-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide A solution of 50 mg (0.089 mmol) of 2-methanesulphonyl-pyrimidine-5-carboxylic acid{1-[4-(4-methoxy-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide (product from Example 149) in 2 mL DMF was combined with 9 mg (0.13 mmol) of potassium cyanide and then heated to 100° C. for 10 minutes in a microwave apparatus. The mixture was then combined with 2 mL concentrated ammonia solution and extracted with dichloromethane. The crude product obtained after evaporation was purified by chromatography (reversed phase HPLC). Yield: 51% of theory C 25 H 20 F 3 N 5 O 4 (511.45) Mass spectrum: [M+H] + =512 EXAMPLE 163 Pyrimidine-5-carboxylic acid{1-[4-(4-acetyl-2-trifluoromethyl-phenoxy)-benzylcarbamoyl]-cyclopropyl}-amide A solution of 70 mg (0.14 mmol) of pyrimidine-5-carboxylic acid(1-{4-[4-(1-hydroxyethyl)-2-trifluoromethyl-phenoxy]-benzylcarbamoyl}-cyclopropyl)amide (product from Example 153) in 10 mL dichloromethane was combined with 300 mg (3.5 mmol) of manganese dioxide and stirred for three days at ambient temperature. The mixture was then filtered and evaporated down. The crude product thus obtained was purified by chromatography (reversed phase HPLC). Yield: 21% of theory C 25 H 21 F 3 N 4 O 4 (498.45) Mass spectrum: [M+H] + =499 The remaining compounds are prepared analogously to the foregoing Examples. Table of End Compounds: EductMethod ofNo.Structure(benzylamine)manufactureLCMS(1)1d)1e)[M − H]− = 457/459(2)2c)analogously to 1e)[M + H]+ = 455/457(3)3b)analogously to 1e)[M + H]+ = 429/431(4)3b)analogously to 1e)[M + H]+ = 441/443(5)3b)analogously to 1e)[M + H]+ = 445/447(6)6b)analogously to 1e)[M + H]+ = 423/425(7)7b)7c)[M + H]+ = 437(8)8b)analogously to 7c)[M + H]+ = 487(9)9b)analogously to 7c)[M + H]+ = 432(10)10b)analogously to 7c)[M + H]+ = 417(11)11b)analogously to 7c)[M + H]+ = 447(12)12b)analogously to 7c)[M + H]+ = 451(13)13b)analogously to 7c)[M + H]+ = 449(14)14c)analogously to 7c)[M + H]+ = 486(15)15c)analogously to 7c)[M + H]+ = 432(16)16c)analogously to 7c)[M + H]+ = 432(17)17b)analogously to 7c)[M + H]+ = 457(18)18b)analogously to 7c)[M + H]+ = 407(19)19c)analogously to 7c)[M + H]+ = 486(20)20b)analogously to 7c)[M + H]+ = 441/443(21)21b)analogously to 7c)[M + H]+ = 475/477/479(22)22b)analogously to 7c)[M + H]+ = 475/477/479(23)23b)analogously to 7c)[M + H]+ = 459/461(24)commercially obtainableanalogously to 7c)[M + H]+ = 419(25)commercially obtainableanalogously to 7c)[M + H]+ = 525(26)commercially obtainableanalogously to 7c)[M + H]+ = 403(27)commercially obtainableanalogously to 7c)[M + H]+ = 457(28)commercially obtainableanalogously to 7c)[M + H]+ = 419(29)commercially obtainableanalogously to 7c)[M + H]+ = 423/425(30)commercially obtainableanalogously to 7c)[M + H]+ = 403(31)commercially obtainableanalogously to 7c)[M + H]+ = 407(32)commercially obtainableanalogously to 7c)[M + H]+ = 407(33)commercially obtainableanalogously to 7c)[M + H]+ = 407(34)commercially obtainableanalogously to 7c)[M − H]− = 387(35)commercially obtainableanalogously to 7a, b, c)[M + H]+ = 451(36)commercially obtainableanalogously to 7a, b, c)[M + H]+ = 437(37)commercially obtainableanalogously to 7a, b, c)[M + H]+ = 455/457(38)commercially obtainableanalogously to 7a, b, c)[M + H]+ = 471/473(39)39b)analogously to 7c)[M + H]+ = 433(40)40b)analogously to 7c)[M + H]+ = 441/443(41)41b)analogously to 7c)[M + H]+ = 437/439(42)commercially obtainableanalogously to 7c)[M + H]+ = 403(43)43b)analogously to 7c)[M + H]+ = 437(44)44b)analogously to 7c)[M + H]+ = 455/457(45)45b)analogously to 7c)[M + H]+ = 451(46)46b)analogously to 1e)[M + H]+ = 481/483(47)47b)analogously to 1e)[M + H]+ = 466/468(48)48b)analogously to 1e)[M + H]+ = 467/469(49)49a)analogously to 7c)[M + H]+ = 431(50)50a)analogously to 7c)[M + H]+ = 475(51)51a)analogously to 7c)[M + H]+ = 433(52)52a)analogously to 7c)[M + H]+ = 473(53)53a)analogously to 7c)[M + H]+ = 453/455(54)54a)analogously to 7c)[M + H]+ = 437/439(55)55a)analogously to 7c)[M + H]+ = 441/443(56)56a)analogously to 7c)[M + H]+ = 457/459/461(57)57a)analogously to 7c)[M + H]+ = 457/459/461(58)58a)analogously to 7c)[M + H]+ = 441/443(59)59a)analogously to 7c)[M + H]+ = 417(60)60a)analogously to 7c)[M + H]+ = 443(61)61a)analogously to 7c)[M + H]+ = 457/459/461(62)62a)analogously to 7c)[M + H]+ = 437/439(63)63a)analogously to 7c)[M + H]+ = 497/499(64)64a)analogously to 7c)[M + H]+ = 457(65)65a)analogously to 7c)[M + H]+ = 473(66)66a)analogously to 7c)[M + H]+ = 445(67)67a)analogously to 7c)[M + H]+ = 454(68)68a)analogously to 7c)[M + H]+ = 453/455(69)69a)analogously to 7c)[M + H]+ = 453/455(70)70a)analogously to 7c)[M + H]+ = 488/490(71)71a)analogously to 7c)[M + H]+ = 437/439(72)72a)analogously to 7c)[M + H]+ = 461(73)73a)analogously to 7c)[M + H]+ = 449(74)74b)74c)[M + H]+ = 457/9/61(75)75c)analogously to 74c)[M + H]+ = 471/3/5(76)76c)76d)[M + H]+ = 473/5/7(77)53a)77a)[M − H]− = 441/443(78)78c)78d)[M − H]− = 499/501/3(79)79c)analogously to 78d)[M + H]+ = 535/7(80)80c)analogously to 78d)[M + H]+ = 501/3/5(81)81c)81d)[M − H]− = 467(82)82f)analogously to 76d)[M + H]+ = 501(83)53a)83a)[M + H]+ = 520(84)84a)84b)[M + H]+ = 487(85)84a)85b)[M + H]+ = 494(86)84a)analogously to 85b)[M + H]+ = 491(87)84a)analogously to 85b)[M + H]+ = 480(88)84a)analogously to 85b)[M + H]+ = 508(89)84a)analogously to 85b)[M + H]+ = 486(90)84a)analogously to 85b)[M + H]+ = 466(91)84a)analogously to 85b)[M + H]+ = 437(92)84a)analogously to 85b)[M + H]+ = 453(93)84a)analogously to 85b)[M + H]+ = 449(94)84a)analogously to 85b)[M + H]+ = 465(95)84a)analogously to 85b)[M + H]+ = 489(96)84a)analogously to 85b)[M + H]+ = 489(97)84a)analogously to 85b)[M + H]+ = 463(98)84a)analogously to 85b)[M + H]+ = 485(99)84a)analogously to 85b)[M + H]+ = 486(100)84a)100a)[M + H]+ = 448(101)84a)analogously to 100a)[M + H]+ = 423(102)84a)analogously to 100a)[M + H]+ = 477(103)84a)analogously to 100a)[M + H]+ = 476(104)84a)analogously to 78d)[M + H]+ = 501(105)84a)analogously to 78d)[M + H]+ = 439(106)84a)106a)[M + H]+ = 490(107)84a)107a), analogously to 106a)[M + H]+ = 506(108)84a)108a), analogously to 106a)[M + H]+ = 490(109)84a)109a)[M + H]+ = 495(110)84a)analogously to 109a)[M + H]+ = 516(111)84a)analogously to 109a)[M + H]+ = 494(112)84a)analogously to 109a)[M + H]+ = 480(113)84a)113a)[M + H]+ = 516(114)84a)114a)[M + H]+ = 467(115)84a)analogously to 109a)[M + H]+ = 466(116)84a)116a), analogously to 109a)[M + H]+ = 516(117)84a)analogously to 107a)[M + H]+ = 502(118)84a)118a)[M + H]+ = 502(119)84a)119a), analogously to 118a)[M + H]+ = 516(120)84a)120a)[M + H]+ = 504(121)84a)analogously to 120a)[M + H]+ = 487(122)84a)analogously to 120a)[M + H]+ = 554(123)84a)analogously to 78d)[M + H]+ = 502(124)84a)analogously to 78d)[M + H]+ = 502(125)84a)125a)[M + H]+ = 476(126)84a)analogously to 120a)[M + H]+ = 475(127)84a)analogously to 78d)[M + H]+ = 538(128)84a)analogously to 78d)[M + H]+ = 501(129)84a)129a)[M + H]+ = 500(130)84a)analogously to 129a)[M + H]+ = 500(131)84a)analogously to 125a)[M + H]+ = 492(132)84a)analogously to 109[M + H]+ = 495(133)84a)analogously to 109[M + H]+ = 494(134)84a)analogously to 109[M + H]+ = 508(135)84a)analogously to 109[M + H]+ = 480(136)84a)analogously to 129[M + H]+ = 492(137)84a)analogously to 129[M + H]+ = 520(138)84a)analogously to 129[M + H]+ = 520(139)[M + H]+ = 481(140)[M + H]+ = 482(141)85analogously to 1e)[M + H]+ = 433(142)84a)analogously to 129[M + H]+ = 502(143)84a)analogously to 129[M + H]+ = 516(144)84a)analogously to 129[M + H]+ = 533(145)86analogously to 1e)[M + H]+ = 467(146)analogously to 140[M + H]+ = 414 [M − H]− = 412(147)analogously to 140[M + H]+ = 444 [M − H]− = 442(148)[M + H]+ = 549(149)[M + H]+ = 565(150)84a)analogously to 129[M + H]+ = 502(151)87analogously to 1e)[M + H]+ = 515(152)[M + H]+ = 512(153)88analogously to 1e)[M + H]+ = 501(154)89analogously to 1e)[M + H]+ = 491(155)90analogously to 1e)[M + H]+ = 515(156)91analogously to 1e)[M + H]+ = 485 [M − H]− = 483(157)analogously to 140[M + H]+ = 448(158)analogously to 140[M + H]+ = 492/94(159)analogously to 140[M + H]+ = 482(160)analogously to 140[M + H]+ = 428(161)analogously to 139[M + H]+ = 501 [M − H]− = 499(162)analogously to 140[M + H]+ = 432 [M − H]− = 430(163)[M + H]+ = 499 Table of Intermediate Compounds III (III)Method ofNo.StructuremanufactureLCMS(1d)(1d)[M + H]+ = 270/272(2c)(2c)[M − NH2]− = 249/251(3b)analogously to (1d)[M + H]+ = 252/254(7b)(7a, b)[M − NH2]+ = 231(8b)analogously to (7a, b)[M − NH2]+ = 281(9b)(9a, b)[M − NH2]+ = 226(10b)(10a, b)[M − NH2]+ = 211(11b)analogously to (7a, b)[M − NH2]+ = 241(12b)analogously to (7a, b)[M − NH2]+ = 245(13b)analogously to (7a, b)[M − NH2]+ = 243(14c)analogously to (9a, b)[M − NH2]+ = 280(15c)analogously to (9a, b)[M − NH2]+ = 226(16c)analogously to (9a, b)[M − NH2]+ = 226(17b)analogously to (8a, b)[M − NH2]+ = 251(18b)analogously to (7a, b)[M − NH2]+ = 201(19c)analogously to (9a, b)[M − NH2]+ = 280(20b)analogously to (7a, b)[M − NH2]+ = 235(21b)analogously to (7a, b)[M + H]+ = 286/288/290(22b)analogously to (7a, b)[M − NH2]+ = 269/71/73(23b)analogously to (7a, b)[M + H]+ = 270/272(39b)(39a, b)[M − NH2]+ = 269/71/73(40b)(40a, b)[M + H]+ = 252/254(41b)analogously to (39a, b)[M − NH2]+ = 231/233(43b)(43a, b)[M − NH2]+ = 231(44b)(44a, b)[M − NH2]+ = 249/251(45b)analogously to (44a, b)[M − NH2]+ = 245(46b)analogously to (1d)[M − NH2]+ = 275/277(49a)(49a)[M − NH2]+ = 225(50a)analogously to (49a)[M − NH2]+ = 269(51a)analogously to (49a)[M − NH2]+ = 227(52a)analogously to (49a)[M − NH2]+ = 267(53a)analogously to (49a)[M − NH2]+ = 247(54a)analogously to (49a)[M − NH2]+ = 231(55a)analogously to (49a)[M − NH2]+ = 235(56a)analogously to (49a)[M − NH2]+ = 251/253(57a)analogously to (49a)[M − NH2]+ = 251/253(58a)analogously to (49a)[M − NH2]+ = 235(59a)analogously to (49a)[M − NH2]+ = 211(60a)analogously to (49a)[M − NH2]+ = 237(61a)analogously to (49a)[M − NH2]+ = 251/253(62a)analogously to (49a)[M − NH2]+ = 231(63a)analogously to (49a)[M − NH2]+ = 291/293(64a)analogously to (49a)[M − NH2]+ = 251(65a)analogously to (49a)[M − NH2]+ = 267(66a)analogously to (49a)[M − NH2]+ = 239(67a)analogously to (49a)[M − NH2]+ = 248(68a)analogously to (49a)[M − NH2]+ = 247(69a)analogously to (49a)[M − NH2]+ = 247(70a)analogously to (49a)[M − NH2]+ = 282(71a)analogously to (49a)[M − NH2]+ = 231(72a)analogously to (49a)[M − NH2]+ = 255(73a)analogously to (49a)[M − NH2]+ = 243(74b)(74a, b)[M + H]+ = 268/70/2(75c)(75a, b, c)[M + H]+ = 282/4/6(76c)(76a, b, c)[M − NH4]+ = 267/9/71(78c)(78a, b, c)[M + H]+ = 295/7/9(79c)(79a, b, c)[M + H]+ = 346/8(80c)analogously to (79a, b, c)[M − NH2]+ = 295/7/9(81c))(81a, b, c)[M + H − NH3]+ = 263(82f))(82c, d, e, f)M*+ = 311(84a))analogously to (82c) and (84a)[M − NH2]+ = 281(85)analogously to (49a)[M + H − NH3]+ = 227(86)analogously to (49a)(87)analogously to (49a)[M + H − NH3]+ = 309(88)[M + H − NH3]+ = 295(89)analogously to (49a)[M + H − NH3]+ = 285 [M + H]+ = 302(90)[M + H − NH3]+ = 309(91)analogously to (49a)[M + H]+ = 296 The following Examples describe pharmaceutical formulations which contain as active substance any desired compound of general formula I, but without restricting the scope of the present invention thereto: EXAMPLE I Dry Ampoule with 75 mg of Active Compound per 10 ml Composition: Active compound75.0mgMannitol50.0mgWater for injectionad 10.0ml Production: Active compound and mannitol are dissolved in water. The charged ampoules are freeze dried. Water for injection is used to dissolve to give the solution ready for use. EXAMPLE II Tablet with 50 mg of Active Compound Composition: (1) Active compound50.0 mg(2) Lactose98.0 mg(3) Maize starch50.0 mg(4) Polyvinylpyrrolidone15.0 mg(5) Magnesium stearate2.0 mg215.0 mg Production: (1), (2) and (3) are mixed and granulated with an aqueous solution of (4). (5) is admixed to the dry granules. Tablets are compressed from this mixture, biplanar with a bevel on both sides and dividing groove on one side. Diameter of the tablets: 9 mm. EXAMPLE III Tablet with 350 mg of Active Compound Composition: (1) Active compound350.0 mg(2) Lactose136.0 mg(3) Maize starch80.0 mg(4) Polyvinylpyrrolidone30.0 mg(5) Magnesium stearate4.0 mg600.0 mg Production: (1), (2) and (3) are mixed and granulated with an aqueous solution of (4). (5) is admixed to the dry granules. Tablets are compressed from this mixture, biplanar with a bevel on both sides and dividing groove on one side. Diameter of the tablets: 12 mm. EXAMPLE IV Capsule with 50 mg of Active Compound Composition: (1) Active compound50.0 mg(2) Maize starch dried58.0 mg(3) Lactose powdered50.0 mg(4) Magnesium stearate2.0 mg160.0 mg Production: (1) is triturated with (3). This trituration is added to the mixture of (2) and (4) with vigorous mixing. This powder mixture is packed into hard gelatine two-piece capsules of size 3 in a capsule-filling machine. EXAMPLE V Capsules with 350 mg of Active Compound Composition: (1) Active compound350.0 mg(2) Maize starch dried46.0 mg(3) Lactose powdered30.0 mg(4) Magnesium stearate4.0 mg430.0 mg Production: (1) is triturated with (3). This trituration is added to the mixture of (2) and (4) with vigorous stirring. This powder mixture is packed into hard gelatine two-piece capsules of size 0 in a capsule-filling machine. EXAMPLE VI Suppositories with 100 mg of Active Compound 1 Suppository Comprises: Active compound100.0 mgPolyethylene glycol (M.W. 1500)600.0 mgPolyethylene glycol (M.W. 6000)460.0 mgPolyethylene sorbitan monostearate840.0 mg2000.0 mg","lang":"en","source":"USPTO_FULLTEXT","data_format":"ORIGINAL"}},"description_lang":["en"],"has_description":true,"has_docdb":true,"has_inpadoc":true,"has_full_text":true,"biblio_lang":"en"},"jurisdiction":"US","collections":[],"usersTags":[],"lensId":"052-919-585-977-36X","publicationKey":"US_8916589_B2","displayKey":"US 8916589 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NORBERT","valueNormalised":"Hauel Norbert"},"inventorship":null},{"name":{"value":"CECI ANGELO","valueNormalised":"Ceci Angelo"},"inventorship":null},{"name":{"value":"CEREDA ENZO","valueNormalised":"Cereda Enzo"},"inventorship":null},{"name":{"value":"DOODS HENRI","valueNormalised":"Doods Henri"},"inventorship":null},{"name":{"value":"KONETZKI INGO","valueNormalised":"Konetzki Ingo"},"inventorship":null},{"name":{"value":"MACK JUERGEN","valueNormalised":"Mack Juergen"},"inventorship":null},{"name":{"value":"PRIEPKE HENNING","valueNormalised":"Priepke Henning"},"inventorship":null},{"name":{"value":"SCHULER-METZ ANNETTE","valueNormalised":"Schuler-metz Annette"},"inventorship":null},{"name":{"value":"WALTER RAINER","valueNormalised":"Walter Rainer"},"inventorship":null}],"inventorships":[],"unmatchedInventorships":[],"activeUserHasInventorship":false},"simpleFamilyId":187572890,"citesPatentCount":21,"countrySpec":{"countryName":"USA","description":"GRANTED PATENT AS SECOND PUBLICATION [FROM 2001 ONWARDS]","rule":"pubdate:AFTER:01-01-2001","docType":"GRANTED_PATENT"},"pageTitle":"US 8916589 B2 - Bradykinin B1-antagonists","documentTitle":"Bradykinin B1-antagonists"},"claims":{"source":"xml_claims","claims":[{"lines":["A compound of the formula I\nwherein\n
R1 denotes\n\n(a) a C1-6-alkyl group optionally substituted by a group R1.1,\n(b) a C1-3-alkyl group wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n(c) a C3-6-cycloalkyl group optionally substituted by a group R1.2,\n(d) a C2-6-alkenyl group,\n(e) a C2-6-alkynyl group,\n(f) an aryl-C1-2-alkylene group optionally substituted by 1, 2 or 3 groups R1.3,\n(g) a five-membered heteroaryl group optionally substituted by by 1, 2 or 3 groups R1.4, which contains at least one N, O or S atom and optionally also contains one, two or three further N atoms and may additionally be benzo-fused,\n(h) a six-membered heteroaryl group optionally substituted by a group R1.4, which contains one, two or three N atoms and may additionally be benzo-fused,\n(i) —O—R1.1.1 or\n(j) —NR1.1.2R1.1.4,\n
R1.1 denotes halogen, —NO2, —CN, C3-6-cycloalkyl, —OR1.1.1, —SR1.1.1, —C(O)R1.1.1, —S(O)2—R1.1.2, —O—S(O)2—R1.1.1, —CO2R1.1.1, —O—C(O)—R1.1.1 , —NR1.1.3R1.1.4, —NR1.1.3-C(O)—R1.1.1, —NR1.1.3- C(O)—R1.1.1, —NR1.1.3-CO2—R1.1.1, —C(O)—NR1.1.3R1.1.4,\n
R1.1.1 denotes\n\n(a) H,\n(b) C1-4-alkyl,\n(c) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n(d) a phenyl group optionally substituted by 1, 2 or 3 groups R1.1.1.1,\n(e) C3-6-cycloalkyl,\n(f) a pyridyl group optionally substituted by 1, 2 or 3 groups R1.1.1.2,\n
R1.1.1.1 independently of one another denote\n\n(b) halogen, —NO2, —CN, —OH, —O—C1-4-alkyl, C3-6-cycloalkyl, C1-4-alkyl,\n(c) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n
R1.1.1.2 independently of one another denote halogen or C1-4-alkyl,\n
R1.1.2 denotes\n\n(a) C1-4-alkyl,\n(b) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n(c) —O—C1-4-alkyl,\n(d) a phenyl group optionally substituted by 1, 2 or 3 groups R1.1.1.1,\n
R1.1.3,\n
R1.1.4 independently of one another denote\n\n(a) H,\n(b) a C1-4-alkyl group optionally substituted by 1, 2 or 3 groups R1.1.4.1,\n(c) a phenyl group optionally substituted by 1, 2 or 3 groups R1.1.1.1,\n(d) C3-6-cycloalkyl, or\n
R1.1.3 and R1.1.4 together with the N atom to which they are bound form a 4-, 5- or 6-membered heterocyclic ring, which may additionally contain a further heteroatom selected from N, O and S, or\n
R1.1.3 and R1.1.4 together with the N atom to which they are bound form a cyclic imide,\n
R1.1.4.1 independently of one another denote halogen, —NH2, —NH(C1-4-alkyl), —N(C1-4-alkyl)2 or —SO2—R1.1.2,\n
R1.2 denotes halogen, —NO2, —CN or phenyl,\n
R1.3 denotes\n\n(a) halogen, —NO2, —CN, —OR1.1.1, —SR1.1.1, —CO2R1.1.1, C1-6-alkyl,\n(b) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n
R1.4 independently of one another denote\n\n(a)\nhalogen, —NO2, —CN, —OR1.1.1, —SR1.1.1, —S(O)—R1.1.2 , —NR1.1.3R1.1.4, C1-6-alkyl,\n(b) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or\n(c) an oxo group,\n
R2 denotes\n\n(a) H, C1-4-alkyl or\n(b) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n
R3 independently of one another denote\n\n(a) H, halogen, —CN, —OH, C1-6-alkyl, C3-7-cycloalkyl, —O—C1-4-alkyl, —O—CF3, —O—C3-6-cycloalkyl, —N(C1-3-alkyl)2, —C(O)—NH2, —(SO2)NH2, —SO2—C1-3-alkyl,\n(b) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n
R4, R5,\n
R6, R7,\n
R8 independently of one another denote\n\n(a) H, halogen, —CN, —OH,\n(b) C1-6-alkyl, wherein two adjacent substituents together may denote a trimethylene or tetramethylene group,\n(c) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n(d) C3-7-cycloalkyl,\n(e) —O—C1-6-alkyl, wherein two adjacent substituents may denote a methylenedioxy or ethylenedioxy group,\n(f) —O—CF3, —O—C3-7-cycloalkyl,\n(g) —NH2, —NH(C1-3-alkyl), —N(C1-3-alkyl)2,\n(h) —C(O)—R8.1 ,\n(i) —SO2—R8.2,\n(j) a five-membered heteroaryl group optionally substituted by one or two C1-3-alkyl groups which is selected from among pyrrolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, imidazolyl, pyrazolyl, triazolyl and tetrazolyl,\n(k) a six-membered heteroaryl group optionally substituted by one or two C1-3-alkyl groups which is selected from among pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl and triazinyl,\n
R8.1 denotes —NH2, —NH(C1-6-alkyl),—N(C1-6-alkyl)2, N-acetidinyl, N-pyrrolidinyl, N-piperidinyl, N-morpholinyl, —OH, —O—C1-8-alkyl, —O—C3-7-cycloalkyl,\n
R8.2 denotes —NH2, —NH(C1-6-alkyl),—N(C1-6-alkyl)2, N-acetidinyl, N-pyrrolidinyl, N-piperidinyl, N-morpholinyl and\n
n denotes one of the numbers 0, 1, 2, 3 or 4,\nor a salt thereof."],"number":1,"annotation":false,"claim":true,"title":false},{"lines":["A compound of the formula I according to claim 1, wherein\n
R1 denotes\n\n(a) a C1-6-alkyl group optionally substituted by a group R1.1,\n(b) a C1-3-alkyl group wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n(c) a C3-6-cycloalkyl group optionally substituted by a group R1.2,\n(e) a five-membered heteroaryl group optionally substituted by a group R1.4, which contains at least one N, O or S atom and which optionally additionally contains one, two or three further N atoms, or\n(f) a six-membered heteroaryl group optionally substituted by a group R1.4, which contains one, two or three N atoms,\n
R1.1 denotes C3-6-cycloalkyl, —OR1.1.1, —NR1.1.3R1.1.4, —C(O)—NR1.1.3R1.1.4, —CN, —CO2R1.1.1, —S(O)2—C1-6-alkyl or —O—S(O)2—C1-6-alkyl,\n
R1.1.1 denotes\n\n(a) H,\n(b) C1-4-alkyl,\n(c) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or\n(d) C3-6-cycloalkyl,\n
R1.1.3,\n
R1.1.4 independently of one another denote\n\n(a) H,\n(b) C1-4-alkyl or\n(c) C3-6-cycloalkyl, and\n
R1.2 denotes halogen, —NO2, —CN or phenyl,\n
R1.3 denotes\n\n(a) halogen, —NO2, —CN, —OR1.1.1, —SR1.1.1, —CO2R1.1.1, C1-6-alkyl or\n(b) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, and\n
R1.4 denotes\n\nor a salt thereof."],"number":2,"annotation":false,"claim":true,"title":false},{"lines":["A compound of the formula I according to claim 1, wherein\n(a) halogen, —NO2, —CN, —OR1.1.1, —SR1.1.1, —NR1.1.3R1.1.4, C1-6-alkyl,\n(b) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or\n(c) an oxo group,\n
R1 denotes\n\n(a) a C1-6-alkyl group optionally substituted by a group R1.1,\n(b) a C1-3-alkyl group wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n(c) a C3-6-cycloalkyl group optionally substituted by a group R1.2,\n(e) a five-membered heteroaryl group optionally substituted by a group R1.4, which contains at least one N, O or S atom and which optionally additionally contains one, two or three further N atoms, or\n(f) a six-membered heteroaryl group optionally substituted by a group R1.4, which contains one, two or three N atoms,\n
R1.1 denotes C3-6-cycloalkyl, —OR 1.1.1, —NR —C(O)—NR —CN, —CO2R1.1.1, —S(O)2—C1-6-alkyl or —O—S(O)2—C1-6-alkyl,\n
R1.1.1 denotes\n\n(a) H,\n(b) C1-4-alkyl,\n(c) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or\n(d) C3-6-cycloalkyl,\n
R1.1.3,\n
R1.1.4 independently of one another denote\n\n(a) H,\n(b) C1-4-alkyl or\n(c) C3-6-cycloalkyl,\n
R1.2 denotes halogen, —NO2, —CN or phenyl,\n
R1.3 denotes\n\n(a) halogen, —NO2, —CN, —OR1.1.1, —SR1.1.1, —CO2R1.1.1, C1-6-alkyl or\n(b) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n
R1.4 denotes\n\n(a) halogen, —NO2, —CN, —OR1.1.1, —SR1.1.1, —NR1.1.3R1.1.4, C1-6-alkyl,\n(b) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or\n(c) an oxo group\n
R2 denotes H or C1-3-alkyl,\n
R3 independently of one another denote\n\n(a) H, halogen, C1-3-alkyl, —O—C1-3-alkyl or\n(b) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n
R4 denotes H or halogen,\n
R5 denotes\n\n(a) H, halogen,\n(b) C1-3-alkyl,\n(c) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n(d) —O—C1-3-alkyl,\n(e) —C(O)—O—C1-3-alkyl or —C(O)—NH2,\n
R6 denotes\n\n(a) H, halogen,\n(b) C1-3-alkylene-R6.1,\n(c) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n(d) —OH, —O—C1-4-alkyl,\n(e) —O—CHF2, —O—CF3,\n(f) —C(O)—O—R6.2, —CN, —C(O)—CH3, —C(O)—NH2 or\n(g) pyrrolyl,\n
R6.1 denotes H, —OH,\n
R6.2 denotes H, C1-3-alkyl,\n
R7 denotes\n\n(a) H, halogen,\n(b) C1-3-alkyl,\n(c) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n(d) —O—C1-3-alkyl,\n(e) —C(O)—NH2 or —C(O)-pyrrolidinyl, and\n
R8 denotes\n\n(a) H, halogen,\n(b) C1-4-alkyl,\n(c) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n(d) —O—C1-3-alkyl,\n(e) —O—CF3,\n(f) —CN, —C(O)—NH2 or\n(g) pyrrolyl,\n
or a salt thereof."],"number":3,"annotation":false,"claim":true,"title":false},{"lines":["A compound of the formula formula I according to claim 1, wherein\n
R1 denotes\n\n(a) a C1-6-alkyl group optionally substituted by a group R1.1,\n(b) a C1-3-alkyl group wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n(d) a five-membered heteroaryl group optionally substituted by a group R1.4, which is selected from among furanyl, isoxazolyl, isothiazolyl, oxazolyl, thiazolyl, pyrazolyl, thiadiazolyl, oxadiazolyl, triazolyl, tetrazolyl, imidazolyl, indolyl, thienyl, pyrrolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl and benzisoxazinyl, or\n(e) a six-membered heteroaryl group optionally substituted by a group R1.4, which is selected from among pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, quinazolinyl and quinoxazinyl,\n
R1.1 denotes C3-6-cycloalkyl, —OR —NR1.1.3R1.1.4, —C(O)—NR1.1.3R1.1.4, —CN, —CO2R1.1.1, —S(O)2-C1-6-alkyl or —O—S(O)2—C1-6-alkyl,\n
R1.1.1 denotes\n\n(a) H,\n(b) C1-4-alkyl,\n(c) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or\n(d) C3-6-cycloalkyl,\n
R1.1.3,\n
R1.1.4 independently of one another denote\n\n(a) H,\n(b) C1-4-alkyl or\n(c) C3-6-cycloalkyl,\n
R1.3 denotes\n\n(a) halogen, —NO2, —CN, —OR1.1.1, —SR1.1.1, —CO2R1.1.1, C1-6-alkyl or\n(b) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, and\n
R1.4 denotes\n\nor a salt thereof."],"number":4,"annotation":false,"claim":true,"title":false},{"lines":["A compound of the formula I according to claim 1, wherein R1 denotes\n\n\nor a salt thereof."],"number":5,"annotation":false,"claim":true,"title":false},{"lines":["A compound of the formula I according to claim 1, wherein\n(a) halogen, —NO2, —CN, —OR1.1.1, —SR1.1.1, C1-6-alkyl,\n(b) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms, or\n(c) an oxo group,\n
R2 denotes H or C1-3-alkyl,\nor a salt thereof."],"number":6,"annotation":false,"claim":true,"title":false},{"lines":["A compound of the formula I according to claim 1, wherein\n
R3 independently of one another denote\n\nor a salt thereof."],"number":7,"annotation":false,"claim":true,"title":false},{"lines":["A compound of the formula I according to claim 1, wherein\n(a) H, halogen, C1-3-alkyl, —O—C1-3-alkyl or\n(b) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n
R4 denotes H or halogen,\nor a salt thereof."],"number":8,"annotation":false,"claim":true,"title":false},{"lines":["A compound of the formula I according to claim 1, wherein\n
R5 denotes\n\nor a salt thereof."],"number":9,"annotation":false,"claim":true,"title":false},{"lines":["A compound of the formula I according to claim 1, wherein\n(a) H, halogen,\n(b) C1-3-alkyl,\n(c) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n(d) —O—C1-3-alkyl,\n(e) —C(O)—O—C1-3-alkyl or —C(O)—NH2,\n
R6 denotes\n\n(a) H, halogen,\n(b) C1-3-alkylene—R6.1,\n(c) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n(d) —OH, —O—C14-alkyl,\n(e) —OCHF2, —O—CF3,\n(f) —C(O)—O—R6.2, —CN, —C(O)—CH3, —C(O)—NH2 or\n(g) pyrrolyl,\n
R6.1 denotes H or —OH and\n
R6.2 denotes H or C1-3-alkyl,\nor a salt thereof."],"number":10,"annotation":false,"claim":true,"title":false},{"lines":["A compound of the formula I according to claim 1, wherein\n
R7 denotes\n\nor a salt thereof."],"number":11,"annotation":false,"claim":true,"title":false},{"lines":["A compound of the formula I according to claim 1, wherein\n(a) H, halogen,\n(b) C1-3-alkyl,\n(c) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n(d) —O—C1-3-alkyl,\n(e) —C(O)—NH2 or —C(O)-pyrrolidinyl,\n
R8 denotes\n\nor a salt thereof."],"number":12,"annotation":false,"claim":true,"title":false},{"lines":["A compound of the formula I according to claim 1, wherein\n(a) H, halogen,\n(b) C14-alkyl,\n(c) C1-3-alkyl, wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,\n(d) —O—C1-3-alkyl,\n(e) —O—CF3,\n(f) —CN, —C(O)—NH2 or\n(g) pyrrolyl,\n
R1 denotes\n\n
R2 denotes H or —CH3,\n
R3 denotes H, F, —CF3, —CH3 or —O—CH3,\n
R4 denotes H or Cl,\n
R5 denotes H, Cl, C1-3-alkyl, —CF3, —O—C1-3-alkyl, —C(O)—O—C1-3-alkyl or —C(O)—NH2,\n
R6 denotes H, F, Cl, C1-3-alkyl, —CF3, —O—C1-4-alkyl, —OCF3, —C(O)—NH2 or pyrrolyl,\n
R7 denotes H, F, Cl, C1-3-alkyl, —CF3, —O—C1-3-alkyl, —C(O)—NH2 or —C(O)-pyrrolidinyl, and\n
R8 denotes H, F, Cl, Br, C1-4-alkyl, —CF3, —O—C1-3-alkyl, —OCF3, —C(O)—NH2, —OCF3 or pyrrolyl,\nor a salt thereof."],"number":13,"annotation":false,"claim":true,"title":false},{"lines":["A compound of the formula I according to claim 1, wherein\n
R1 denotes\n\n\n\n
R2 denotes H, —CH3 or —C2H5,\n
R3 denotes H, F, Cl, —CF3, —CH3 or —O—CH3,\n
R4 denotes H or Cl,\n
R5 denotes H, Cl, C1-3-alkyl, —CF3, —O—C1-3-alkyl, —C(O)—O—C1-3-alkyl or —C(O)—NH2,\n
R6 denotes H, F, Cl, Br, —CN, C1-3-alkyl, —CF3, —COOH, —COO—C1-3-alkyl, —CH(OH)CH3, —OH, —O—C1-4-alkyl, —OCF3, —OCHF2, —C(O)—CH3, —C(O)—NH2 or pyrrolyl,\n
R7 denotes H, F, Cl, C1-3-alkyl, —CF3, —O—C1-3-alkyl, —C(O)—NH2 or —C(O)-pyrrolidinyl and\n
R8 denotes H, F, Cl, Br, —CN,\nC1-4-alkyl, —CF3, —O—C1-3-alkyl, —OCF3, —C(O)—NH2, —OCF3 or pyrrolyl,or a salt thereof."],"number":14,"annotation":false,"claim":true,"title":false},{"lines":["A compound of the formula I according to claim 1, selected from the group consisting of:\nNo.Structure(1)\n (2)\n (3)\n (4)\n (5)\n (6)\n (7)\n (8)\n (9)\n (10)\n (11)\n (12)\n (13)\n (14)\n (15)\n (16)\n (17)\n (18)\n (19)\n (20)\n (21)\n (22)\n (23)\n (24)\n (25)\n (26)\n (27)\n (28)\n (29)\n (30)\n (31)\n (32)\n (33)\n (34)\n (35)\n (36)\n (37)\n (38)\n (39)\n (40)\n (41)\n (42)\n (43)\n (44)\n (45)\n (46)\n (47)\n (48)\n (49)\n (50)\n (51)\n (52)\n (53)\n (54)\n (55)\n (56)\n (57)\n (58)\n (59)\n (60)\n (61)\n (62)\n (63)\n (64)\n (65)\n (66)\n (67)\n (68)\n (69)\n (70)\n (71)\n (72)\n (73)\n (74)\n (75)\n (76)\n (77)\n (78)\n (79)\n (80)\n (81)\n (82)\n (83)\n (84)\n (85)\n (86)\n (87)\n (88)\n (89)\n (90)\n (91)\n (92)\n (93)\n (94)\n (95)\n (96)\n (97)\n (98)\n (99)\n (100)\n (101)\n (102)\n (103)\n (104)\n (105)\n (106)\n (107)\n (108)\n (109)\n (110)\n (111)\n (112)\n (113)\n (114)\n (115)\n (116)\n (117)\n (118)\n (119)\n (120)\n (121)\n (122)\n (123)\n (124)\n (125)\n (126)\n (127)\n (128)\n (129)\n (130)\n (131)\n (132)\n (133)\n (134)\n (135)\n (136)\n (137)\n (138)\n (139)\n (140)\n (141)\n (142)\n (143)\n (144)\n (145)\n (146)\n (147)\n (148)\n (149)\n (150)\n (151)\n (152)\n (153)\n (154)\n (155)\n (156)\n (157)\n (158)\n (159)\n (160)\n (161)\n (162)\n (163)\n\nor a salt thereof."],"number":15,"annotation":false,"claim":true,"title":false},{"lines":["A physiologically acceptable salt of a compound as in any one of claims 1-15."],"number":16,"annotation":false,"claim":true,"title":false},{"lines":["A pharmaceutical composition comprising a compound as in any one of claims 1-15, or a physiologically acceptable salt thereof together with an inert carrier or diluents."],"number":17,"annotation":false,"claim":true,"title":false},{"lines":["A method for treating acute pain, visceral pain, neuropathic pain, inflammatory/pain receptor-mediated pain, tumour pain and headache diseases, which method comprises administering to a host suffering from the same a therapeutically effective amount of a compound as in any one of claims 1-15, or a physiologically acceptable salt thereof."],"number":18,"annotation":false,"claim":true,"title":false}]}},"filters":{"npl":[],"notNpl":[],"applicant":[],"notApplicant":[],"inventor":[],"notInventor":[],"owner":[],"notOwner":[],"tags":[],"dates":[],"types":[],"notTypes":[],"j":[],"notJ":[],"fj":[],"notFj":[],"classIpcr":[],"notClassIpcr":[],"classNat":[],"notClassNat":[],"classCpc":[],"notClassCpc":[],"so":[],"notSo":[],"sat":[]},"sequenceFilters":{"s":"SEQIDNO","d":"ASCENDING","p":0,"n":10,"sp":[],"si":[],"len":[],"t":[],"loc":[]}}