{"search_session":{},"preferences":{"l":"en","queryLanguage":"en"},"patentId":"161-066-860-474-960","frontPageModel":{"patentViewModel":{"ref":{"entityRefType":"PATENT","entityRefId":"161-066-860-474-960"},"entityMetadata":{"linkedIds":{"empty":true},"tags":[],"collections":[{"id":11958,"type":"PATENT","title":"Rensselaer Polytechnic Institute Patent Portfolio","description":"","access":"OPEN_ACCESS","displayAvatar":true,"attested":false,"itemCount":2022,"tags":[],"user":{"id":91044780,"username":"Cambialens","firstName":"","lastName":"","created":"2015-05-04T00:55:26.000Z","displayName":"Cambialens","preferences":"{\"usage\":\"public\",\"beta\":false}","accountType":"PERSONAL","isOauthOnly":false},"notes":[{"id":8527,"type":"COLLECTION","user":{"id":91044780,"username":"Cambialens","firstName":"","lastName":"","created":"2015-05-04T00:55:26.000Z","displayName":"Cambialens","preferences":"{\"usage\":\"public\",\"beta\":false}","accountType":"PERSONAL","isOauthOnly":false},"text":"
A is chosen from -CH2-Z, -NHSO2-(loweralkyl),
Q is chosen from O, S and NR17;
Y is chosen from O, S, NR17 and NOH;
Z is chosen from OH, SH and NH2;
R1 is chosen from hydrogen, lower alkoxy, phenyl and -NHR8;
R2 and R2a are both hydrogen or taken together R2 and R2a are =O;
R3 is chosen from hydrogen, lower alkyl, alkenyl, aryl, heterocyclyl, benzyl and hydroxyalkyl;
R4 is chosen from hydrogen, hydroxy, amino, lower alkoxy, C1-C20 alkyl and C1-C20 alkyl substituted with hydroxy or carbonyl;
R5 is lower alkyl;
R6 is lower alkyl;
R7 is hydrogen; ortogether R4, R5, R6 and R7 may form from one to three rings, said rings having optional additional substitution;
R8 is chosen from hydrogen, -OH, NH2 and -CH2R15;
R15 is chosen from hydrogen, alkyl, aryl, substituted aryl and alkyl substituted with alkoxy, amino, alkylamino or dialkylamino;
R16 is chosen from hydrogen and NH2; and
R17 is chosen from hydrogen, alkyl, aryl and benzyl;with the provisos that, (1) when R2 and R2a are hydrogen, R3 is hydrogen or cyclopropyl, R4 is hydroxy, and together R5, R6 and R7 form two rings substituted with a spirodioxolane, A cannot be -COOCH3 or NHSO2CH3; (2) when R2 and R2a are hydrogen, R3 is hydrogen or cyclopropyl, R4 is hydroxy, and together R5, R6 and R7 form the ring system of oxymorphone and naltrexone, A cannot be NHSO2CH3; and (3) when R2, R2a, R4 and R7 are hydrogen, R3 is cyclopropyl and R5 and R6 are methyl, A cannot be NHC(O)H."],"number":1,"annotation":false,"title":false,"claim":true},{"lines":["A compound according to claim 1 wherein A is chosen from the group consisting of: -COOCH3, -COOEt, -CONH2, -C(=S)NH2, -C(O)NHOH, -C(O)NHNH2, -CONHCH3, -CONHBn, -CONHCH2(4-MeOC6H4), 2-(4,5-dihydroimidazolyl), -C(=NOH)NH2, -CH2NH2, CH2OH, -COC6H5, -C(=NOH)C6H5, -NHCHO, -NHCHS and NHSO2CH3."],"number":2,"annotation":false,"title":false,"claim":true},{"lines":["A 2,6-methano-3-benzazocine according to claim 1 or 2 wherein:
R4 is chosen from hydrogen, hydroxy, lower alkoxy, C1-C20 alkyl and C1-C20 alkyl substituted with hydroxy or carbonyl;
R5 is lower alkyl;
R6 is lower alkyl; and
R7 is hydrogen."],"number":3,"annotation":false,"title":false,"claim":true},{"lines":["A 2,6-methano-3-benzazocine according to claim 3 wherein:
R3 is chosen from hydrogen, cyclopropyl, phenyl, vinyl, dimethylvinyl, hydroxycyclopropyl, furanyl, and tetrahydrofuranyl;
R4 is chosen from hydrogen and 3-oxo-5-cyclopentyl-1-pentanyl;
R5 is methyl; and
R6 is methyl or ethyl."],"number":4,"annotation":false,"title":false,"claim":true},{"lines":["A morphinan according to claim 1 or 2 wherein together R5 and R6 form one ring and R7 is hydrogen, said morphinan having the structure:"],"number":5,"annotation":false,"title":false,"claim":true},{"lines":["A morphinan according to claim 5 wherein R2 and R2a are hydrogen; R3 is chosen from hydrogen, cyclopropyl, cyclobutyl, vinyl and tetrahydrofuranyl; and R4 is hydrogen, hydroxy or amino."],"number":6,"annotation":false,"title":false,"claim":true},{"lines":["A morphinan according to claim 1 or 2 wherein together R5, R6 and R7 form two rings, said morphinan having the structure: wherein
R4 is hydrogen, hydroxy, amino or lower alkoxy;
R9 is hydrogen or lower alkyl;
R10 is chosen from hydrogen, lower alkyl and hydroxy(lower alkyl); ortogether, R9 and R10 form a spire-fused carbocycle of 5 to 10 carbons;
R11 is hydrogen;
R12 is chosen from hydroxy, lower alkoxy and -NR13R14;or together, R11 and R12 form a carbonyl or a vinyl substituent; or together, R4 and R11 form a sixth ring."],"number":7,"annotation":false,"title":false,"claim":true},{"lines":["A morphinan according to claim 7, wherein R4 and R11 form a sixth ring, of formula"],"number":8,"annotation":false,"title":false,"claim":true},{"lines":["A morphinan according to claim 8 wherein
R9 is hydrogen;
R10 is hydroxy(lower alkyl); and
R12 is lower alkoxy."],"number":9,"annotation":false,"title":false,"claim":true},{"lines":["A morphinan according to claim 7, wherein R11 and R12 form a carbonyl substituent, of formula:"],"number":10,"annotation":false,"title":false,"claim":true},{"lines":["A morphinan according to claim 10 wherein
R2 and R2a are both hydrogen;
R4 is chosen from hydrogen, hydroxy, amino and lower alkoxy; and
R9 and R10 are both hydrogen ortogether, R9 and R10 form a spiro-fused carbocycle of 5 to 10 carbons."],"number":11,"annotation":false,"title":false,"claim":true},{"lines":["A morphinan according to claim 11 wherein R9 and R10 are both hydrogen."],"number":12,"annotation":false,"title":false,"claim":true},{"lines":["A morphinan according to claim 11, wherein R9 and R10 form a spiro-fused carbocycle, of formula:"],"number":13,"annotation":false,"title":false,"claim":true},{"lines":["A morphinan according to claim 7, wherein R11 and R12 form a vinyl substituent, of formula:"],"number":14,"annotation":false,"title":false,"claim":true},{"lines":["A morphinan according to claim 14 wherein R2 and R2a are both hydrogen; R4 is hydroxy; and R9 and R10 are both hydrogen."],"number":15,"annotation":false,"title":false,"claim":true},{"lines":["A morphinan according to claim 7, wherein R11 is hydrogen and R12 is -NR13R14, of formula:"],"number":16,"annotation":false,"title":false,"claim":true},{"lines":["A morphinan according to claim 7 wherein R2 and R2a are both hydrogen; R4 is hydroxy; R9 and R10 are both hydrogen; and R12 is chosen from: -NH2, -N(CH2CH2Cl)2, and NHC(O)CH=CHCOOCH3."],"number":17,"annotation":false,"title":false,"claim":true},{"lines":["A morphinan according to claim 1 or 2 wherein together R5, R6 and R7 form two rings, said morphinan having the structure:"],"number":18,"annotation":false,"title":false,"claim":true},{"lines":["A morphinan according to claim 7, wherein R4 and R11 form a sixth ring, of formula wherein
R9 is hydrogen;
R10 is hydroxy(lower alkyl); and
R12 is lower alkoxy."],"number":19,"annotation":false,"title":false,"claim":true},{"lines":["A compound of formula: wherein A is chosen from -CH2-Z, -NHSO2-(loweralkyl),
Q is chosen from O, S and NR17;
Y is chosen from O, S, NR17 and NOH;
Z is chosen from OH, SH and NH2;
R1 is chosen from hydrogen, lower alkoxy, phenyl and -NHR8;
R8 is chosen from hydrogen, -OH, -NH2 and -CH2R15;
R15 is chosen from hydrogen, alkyl, aryl, substituted aryl and alkyl substituted with alkoxy, amino, alkylamino or dialkylamino;
R16 is chosen from hydrogen and NH2; and
R17 is chosen from hydrogen, alkyl, aryl and benzyl."],"number":20,"annotation":false,"title":false,"claim":true},{"lines":["A method for preparing a second compound that interacts with an opioid receptor when a first compound that interacts with an opioid receptor is known, said first compound containing a phenolic hydroxyl, said method comprising converting said phenolic hydroxyl to a residue chosen from the group consisting of -COOCH3, -COOEt, -CONH2, -C(=S)NH2, -C(O)NHOH, -C(O)NHNH2, -CONHCH3, -CONHBn, -CONHCH2(4-MeOC6H4), 2-(4,5-dihydroimidazolyl), -C(=NOH)NH2, -CH2NH2, CH2OH, -COC6H5, -C(=NOH)C6H5, NHCHO, -NHCHS and NHSO2CH3, with the provisos that said first compound containing a phenolic hydroxyl cannot be (1) cyclazocine converted to -NHCHO or (2) naltrexone or oxymorphone converted to -NHSO2CH3."],"number":21,"annotation":false,"title":false,"claim":true},{"lines":["A method according to claim 21 wherein said phenolic hydroxyl is converted to a carboxamide, a formamide, a hydroxyamidine or a thioamide."],"number":22,"annotation":false,"title":false,"claim":true},{"lines":["A method according to claim 21 wherein said first compound containing a phenolic hydroxyl is chosen from the group consisting of: and compounds with registry numbers 216531-48-5, 155836-52-5, 361444-66-8, 119193-09-8, 156130-44-8, 151022-07-0, 149710-80-5, 59263-76-2, 469-79-4, 177284-71-8, 189263-70-5,173398-79-3, 189016-07-7, 69926-34-7 and 189015-08-5. wherein
R2 and R2a are both hydrogen or taken together R2 and R2a are =O;
R3 is chosen from hydrogen, lower alkyl, alkenyl, aryl, heterocyclyl, benzyl and hydroxyalkyl;
R4 is chosen from hydrogen, hydroxy, amine, lower alkoxy, C1-C20 alkyl and C1-C20 alkyl substituted with hydroxy or carbonyl;
R5 is lower alkyl;
R6 is lower alkyl; and
R7 is hydrogen; ortogether R4, R5, R6 and R7 may form from one to three rings, said rings having optional additional substitution."],"number":23,"annotation":false,"title":false,"claim":true},{"lines":["A method for decreasing the rate of metabolism of a compound that interacts at an opioid receptor, said compound containing a phenolic hydroxyl, said method comprising converting said phenolic hydroxyl to a residue chosen from the group consisting of -COOCH3, -COOEt, -CONH2, -C(=S)NH2, -C(O)NHOH, -C(O)NHNH2, -CONHCH3, -CONHBn, -CONHCH2(4-MeOC6H4), 2-(4,5-dihydroimidazolyl), -C(=NOH)NH2, -CH2NH2, -CH2OH, -COC6H5, -C(=NOH)C6H5, NHCHO, -NHCHS and -NHSO2CH3."],"number":24,"annotation":false,"title":false,"claim":true},{"lines":["A method for decreasing the rate of metabolism of a compound that interacts at an opioid receptor, said compound containing a phenolic hydroxyl, said method comprising converting said phenolic hydroxyl to a carboxamide, a formamide, a hydroxyamidine or a thioamide."],"number":25,"annotation":false,"title":false,"claim":true},{"lines":["A method according to claim 24 or 25 wherein said first compound containing a phenolic hydroxyl is chosen from the group consisting of: and compounds with registry numbers 216531-48-5,155836-52-5,361444-66-8, 119193-09-8,156130-44-8,151022-07-0,149710-80-5,59263-76-2,469-79-4, 177284-71-8, 189263-70-5,173398-79-3,189016-07-7, 69926-34-7 and 189015-08-5. wherein
R2 and R2a are both hydrogen or taken together R2 and R2a are =O;
R3 is chosen from hydrogen, lower alkyl, alkenyl, aryl, heterocyclyl, benzyl and hydroxyalkyl;
R4 is chosen from hydrogen, hydroxy, amine, lower alkoxy, C1-C20 alkyl and C1-C20 alkyl substituted with hydroxy or carbonyl;
R5 is lower alkyl;
R6 is lower alkyl; and
R7 is hydrogen; ortogether R4, R5, R6 and R7 may form from one to three rings, said rings having optional additional substitution."],"number":26,"annotation":false,"title":false,"claim":true},{"lines":["A method for inhibiting a response mediated by an opioid receptor comprising:
(a) providing a first compound that inhibits an opioid receptor response, said first compound containing a phenolic hydroxyl group;
(b) preparing a second compound that interacts with an opioid receptor by converting said phenolic hydroxyl group to a residue chosen from -CH2-Z, - NHS02-(loweralkyl),Q is chosen from O, S and NR17;Y is chosen from O, S, NR17 and NOH;Z is chosen from OH, SH and NH2;R1 is chosen from lower alkoxy, phenyl and -NHR8;R8 is chosen from hydrogen, -OH, -NH2 and -CH2R15;R15 is chosen from hydrogen, alkyl, aryl, substituted aryl and alkyl substituted with alkoxy, amino, alkylamino or dialkylamino; andR16 is chosen from hydrogen and NH2; andR17 is chosen from hydrogen, alkyl, aryl and benzyl;and
(c) bringing said second compound into contact with said opioid receptor,with the provisos that said first compound containing a phenolic hydroxyl cannot be (1) cyclazocine converted to -NHCHO or (2) naltrexone or oxymorphone converted to -NHSO2CH3."],"number":27,"annotation":false,"title":false,"claim":true},{"lines":["A method according to claim 27 wherein said phenolic hydroxyl group is converted to a carboxamide, a thioamide or a formamide."],"number":28,"annotation":false,"title":false,"claim":true},{"lines":["A method for eliciting or enhancing a response mediated by an opioid receptor comprising:
(a) providing a first compound that elicits or enhances an opioid receptor response, said first compound containing a phenolic hydroxyl group;
(b) preparing a second compound that interacts with an opioid receptor by converting said phenolic hydroxyl group to a residue chosen from -CH2-Z, - NHSO2-(loweralkyl),Q is chosen from O, S and NR17;Y is chosen from O, S, NR17 and NOH;Z is chosen from OH, SH and NH2;R1 is chosen from hydrogen, lower alkoxy, phenyl and -NHR8;R8 is chosen from hydrogen, -OH, -NH2 and -CH2R15;R15 is chosen from hydrogen, alkyl, aryl, substituted aryl and alkyl substituted with alkoxy, amino, alkylamino or dialkylamino;R16 is chosen from hydrogen and NH2; andR17 is chosen from hydrogen, alkyl, aryl and benzyl;
(c) bringing said second compound into contact with said opioid receptor,with the provisos that said first compound containing a phenolic hydroxyl cannot be (1) cyclazocine converted to NHCHO or (2) naltrexone or oxymorphone converted to -NHSO2CH3."],"number":29,"annotation":false,"title":false,"claim":true},{"lines":["A method for treating a disease or condition by altering a response mediated by an opioid receptor comprising bringing into contact with said opioid receptor a compound having the formula wherein A is chosen from -CH2-Z, -NHSO2-(loweralkyl),
Q is chosen from O, S and NR17;
Y is chosen from O, S, NR17 and NOH;
Z is chosen from OH, SH and NH2;
R1 is chosen from hydrogen, lower alkoxy, phenyl and -NHR8;
R8 is chosen from hydrogen, -OH, NH2 and -CH2R15;
R15 is chosen from hydrogen, alkyl, aryl, substituted aryl and alkyl substituted with alkoxy, amino, alkylamino or dialkylamino;
R16 is chosen from hydrogen and NH2; and
R17 is chosen from hydrogen, alkyl, aryl and benzyl; andB represents an appropriate residue such that a known compound alters a response mediated by said opioid receptor with the provisos that said known compound cannot be (1) cyclazocine converted to -NHCHO or (2) naltrexone or oxymorphone converted to -NHSO2CH3."],"number":30,"annotation":false,"title":false,"claim":true},{"lines":["A method according to claim 30 wherein said disease or condition is chosen from the group consisting of pain, pruritis, diarrhea, irritable bowel syndrome, gastrointestinal motility disorder, obesity, respiratory depression, convulsions, coughing, hyperalgesia and drug addiction."],"number":31,"annotation":false,"title":false,"claim":true},{"lines":["A process for converting an opioid-binding phenol to a carboxamide comprising:
(a) reacting a phenol that exhibits binding at an opioid receptor below 25 nM with a reagent to convert said phenol to a group displaceable by CN⊖;
(b) reacting said group displaceable by CN⊖ with Zn(CN)2 in the presence of a Pd(0) catalyst to provide a nitrile; and
(c) hydrolyzing said nitrile to a carboxamide."],"number":32,"annotation":false,"title":false,"claim":true},{"lines":["A process for converting an opioid-binding phenol to a carboxamide comprising reacting a phenol that exhibits binding at an opioid receptor below 25 nM with carbon monoxide and ammonia in the presence of a Pd(0) catalyst to provide a carboxamide."],"number":33,"annotation":false,"title":false,"claim":true},{"lines":["A process for converting an opioid-binding phenol to a hydroxyamidine comprising:
(a) reacting a phenol that exhibits binding at an opioid receptor below 10 nM with a reagent to convert said phenol to a group displaceable by CN⊖;
(b) reacting said group displaceable by CN⊖ with Zn(CN)2 in the presence of a Pd(0) catalyst to provide a nitrile; and
(c) reacting said nitrile with hydroxylamine to produce a hydroxyamidine."],"number":34,"annotation":false,"title":false,"claim":true},{"lines":["A process for converting an opioid-binding phenol to a thiocarboxamide comprising:
(a) reacting a phenol that exhibits binding at an opioid receptor below 10 nM with a reagent to convert said phenol to a group displaceable by CN⊖;
(b) reacting said group displaceable by CN⊖ with Zn(CN)2 in the presence of a Pd(0) catalyst to provide a nitrile;
(c) hydrolyzing said nitrile to a carboxamide; and
(d) reacting said carboxamide with a pentavalent phosphorus-sulfur reagent."],"number":35,"annotation":false,"title":false,"claim":true},{"lines":["A process for converting a phenol on a benzomorphan or morphinane to a carboxamide comprising:
(a) reacting said phenol with a reagent to convert said phenol to a group displaceable by CN⊖;
(b) reacting said group displaceable by CN⊖ with Zn(CN)2 in the presence of a Pd(0) catalyst to provide a nitrile; and
(c) hydrolyzing said nitrile to a carboxamide."],"number":36,"annotation":false,"title":false,"claim":true},{"lines":["A process for converting a phenol on a benzomorphan or morphinane to a carboxamide comprising reacting said phenol with carbon monoxide and ammonia in the presence of a Pd(0) catalyst to provide a benzomorphan or morphinane carboxamide."],"number":37,"annotation":false,"title":false,"claim":true},{"lines":["A process for converting a phenol on a benzomorphan or morphinane to a hydroxyamidine comprising:
(a) reacting said phenol with a reagent to convert said phenol to a group displaceable by CN⊖;
(b) reacting said group displaceable by CN⊖ with Zn(CN)2 in the presence of a Pd(0) catalyst to provide a nitrile; and
(c) reacting said nitrile with hydroxylamine to produce a hydroxyamidine."],"number":38,"annotation":false,"title":false,"claim":true},{"lines":["A process for converting a phenol on a benzomorphan or morphinane to a thiocarboxamide comprising:
(a) reacting said phenol with a reagent to convert said phenol to a group displaceable by CN⊖;
(b) reacting said group displaceable by CN⊖ with Zn(CN)2 in the presence of a Pd(0) catalyst to provide a nitrile;
(c) hydrolyzing said nitrile to a carboxamide; and
(d) reacting said carboxamide with a pentavalent phosphorus-sulfur reagent."],"number":39,"annotation":false,"title":false,"claim":true},{"lines":["A process according to any of claims 32, 34, 35, 36, 38 or 39 wherein said reagent to convert said phenol to a group displaceable by CN⊖ is trifluoromethansulfonic anhydride in the presence of base."],"number":40,"annotation":false,"title":false,"claim":true},{"lines":["A process according to any of claims 32, 34, 35, 36, 38 or 39 wherein said Pd(0) catalyst is tetrakis(triphenylphosphine)palladium."],"number":41,"annotation":false,"title":false,"claim":true},{"lines":["A process for converting an opioid-binding phenol to a carboxamide comprising:
(a) reacting a phenol that exhibits binding at an opioid receptor below 25 nM with a reagent to convert said phenol to a triflate;
(b) reacting said triflate with carbon monoxide and ammonia in the presence of a Pd(II) salt and a Pd(0) catalyst to provide a carboxamide."],"number":42,"annotation":false,"title":false,"claim":true},{"lines":["A process for converting an opioid-binding phenol to a carboxamide comprising:
(a) reacting a phenol that exhibits binding at an opioid receptor below 25 nM with a reagent to convert said phenol to a triflate;
(b) reacting said triflate with carbon monoxide and hexamethyldisilazane in the presence of a Pd(II) salt and a Pd(0) catalyst to provide a silylated carboxamide precursor; and
(c) hydrolyzing said silylated carboxamide precursor to provide a carboxamide."],"number":43,"annotation":false,"title":false,"claim":true},{"lines":["A process for converting a phenol on a benzomorphan or morphinane to a carboxamide comprising:
(a) reacting said phenol with a reagent to convert said phenol to a triflate;
(b) reacting said triffate with carbon monoxide and ammonia in the presence of a Pd(II) salt and a Pd(0) catalyst to provide a carboxamide."],"number":44,"annotation":false,"title":false,"claim":true},{"lines":["A process for converting a phenol on a benzomorphan or morphinane to a carboxamide comprising:
(a) reacting said phenol with a reagent to convert said phenol to a triflate;
(b) reacting said triflate with carbon monoxide and hexamethyldisilazane in the presence of a Pd(II) salt and a Pd(0) catalyst to provide a silylated carboxamide precursor; and
(c) hydrolyzing said silylated carboxamide precursor to provide a carboxamide."],"number":45,"annotation":false,"title":false,"claim":true},{"lines":["A process according to any of claims 42 to 45 wherein said Pd(0) catalyst is generated in situ from Pd(OAc)2 or PdCl2 and 1,1'-bis(diphenylphosphino)-ferrocene."],"number":46,"annotation":false,"title":false,"claim":true}]}},"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":[]}}