Abstract
The present invention relates to chemokine receptor binding compounds, pharmaceutical compositions and their use. More specifically, the present invention relates to modulators of chemokine receptor activity, preferably modulators of CCR5. These compounds demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).
Claims
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A compound or a pharmaceutically acceptable salt thereof, having the formula:
where
n is 0 or 1;
R1 is pyridinyl or pyrimidinyl, each optionally substituted by one or more halogen, alkyl, amine or heteroaryl;
R2 is phenyl, pyridinyl, thiazolyl, furanyl, or thiophenyl, each of which is optionally linked to one or more C1-C6 alkyl, alkoxy, trifluoromethyl, carboxylalkyl, cyano, or halogen;
R3 is phenyl, pyridinyl, thiazolyl, oxazolyl, pyrimidinyl, indolyl, indolinyl, isoindolinyl, 1,3-benzodioxolyl, 1,4-benzodioxanyl, benzofuranyl, 2,3-dihydroxybenzofuranyl or phthalanyl, each of which is optionally linked to one or more C1-C6 alkyl, trifluoromethyl, oxotrifluoromethyl, carboxylalkyl, cyano, halogen, sulfanyl, SO2R9, where R9 is alkyl, amine or amino alkyl, C(O)R10, where R10 is alkyl, amine, morpholine, NMe2, N(OMe)Me, NHPh, piperidine, NHMe, piperazine, NHCH2C(O)OMe or PhC(O)OH, OR11, where R11 is H, alkyl, (CH2)2OMe, CH2C(O)NH2, CH2C(O)NHNH2, CH2C(O)OCMe3, CH2C(O)OMe, CH2C(O)OH, PhC(O)OH, PhC(O)NH2, SO2Me, C(O)Me, C(O)OMe, C(O)NEt2, C(O)NMe2 or
NHR12, where R12 is H, C(O)Me, C(O)CF3, SO2Me, C(O)NH2, C(O)NMe2 or NO2, CH2PhC(O)OH, SOMe, CH2NHC(O)Me, morpholine, CH═CHC(O)OMe, CH═CHC(O)OH, andR4 is hydrogen or alkyl.
- The compound of claim 1, where R4 is hydrogen.
- A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
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A compound or a pharmaceutically acceptable salt thereof, selected from the group consisting of
N-(3-{4-[(4-Bromo-phenyl)-(3-chloro-benzyl)-amino]-piperidin-1-yl}-butyl)-3,5-dichloro-isonicotinamide (62);
N-(3-{4-[Benzyl-(4-cyano-phenyl)-amino]-piperidin-1-yl}-butyl)-3,5-dichloro-isonicotinamide (63);
3,5-Dichloro-N-(3-{4-[(4-cyano-phenyl)-(3-fluoro-benzyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (64);
3,5-Dichloro-N-(3-{4-[(3-chloro-benzyl)-(4-cyano-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (65);
3,5-Dichloro-N-(3-{4-[(4-cyano-phenyl)-(3-methyl-benzyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (66);
N-(3-{4-[Benzyl-(4-trifluoromethyl-phenyl)-amino]-piperidin-1-yl}-butyl)-3,5-dichloro-isonicotinamide (67);
3,5-Dichloro-N-(3-{4-[(3-fluoro-benzyl)-(4-trifluoro-methyl-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (68);
3,5-Dichloro-N-(3-{4-[(3-chloro-benzyl)-(4-trifluoromethyl-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (69);
N-(3-{4-[Benzyl-(4-trifluoromethoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-3,5-dichloro-isonicotinamide (70);
3,5-Dichloro-N-(3-{4-[(3-methyl-benzyl)-(4-trifluoromethoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (71);
3,5-Dichloro-N-(3-{4-[(3-fluoro-benzyl)-(4-methylsulfanyl-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (72);
3,5-Dichloro-N-(3-{4-[(3-chloro-benzyl)-(4-methylsulfanyl-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (73);
3,5-Dichloro-N-(3-{4-[(3-methyl-benzyl)-(4-methylsulfanyl-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (74);
3,5-Dichloro-N-(3-{4-[(3-chloro-benzyl)-(4-methanesulfonyl-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (75);
3,5-Dichloro-N-(3-{4-[(4-methanesulfonyl-phenyl)-(3-methyl-benzyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (76);
3,5-Dichloro-N-(3-{4-[(3-fluoro-benzyl)-(4-methoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (77);
3,5-Dichloro-N-(3-{4-[(3-chloro-benzyl)-(4-methoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (78);
N-(3-{4-Benzyl-(4-methylsulfamoyl-phenyl)-amino]-piperidin-1-yl}-butyl)-3,5-dichloro-isonicotinamide (79);
Methanesulfonic acid 4-[benzyl-(1-{3-[(3,5-dichloro-pyridine-4-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenyl ester (80);
N-(3-{4-[Benzyl-(4-nitro-phenyl)-amino]-piperidin-1-yl}-butyl)-3,5-dichloro-isonicotinamide (81);
3,5-Dichloro-N-(3-{4-[(3-chloro-benzyl)-(4-nitro-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (82);
N-(3-{4-[Benzyl-(4-sulfamoyl-phenyl)-amino]-piperidin-1-yl}-butyl)-3,5-dichloro-isonicotinamide (83);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(3-fluoro-benzyl)-(4-nitro-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (84);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-cyano-phenyl)-(3-fluoro-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (95);
4-{4-[Benzyl-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenoxyl}-benzoic acid (96);
4-{4-[Benzyl-(1-{1-methyl-3-[(4-methyl-pyridine-3-carbonyl)-amino]-propyl}-piperidin-4-yl)-amino]-phenoxyl}-benzoic acid (99);
4-{4-[Benzyl-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-benzyl}-benzoic acid (102);
N-(3-{4-[(4-Bromo-phenyl)-(3-cyano-benzyl)-amino]-piperidin-1-yl}-butyl)-3,5-dichloro-isonicotinamide (103);
3,5-Dichloro-N-(3-{4-[(3-cyano-benzyl)-(4-trifluoro-methyl-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (104);
3,5-Dichloro-N-(3-{4-[(3-cyano-benzyl)-(4-methylsulfanyl-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (105);
3,5-Dichloro-N-(3-{4-[(3-cyano-benzyl)-(4-cyano-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (106);
4-[(3-Cyano-benzyl)-(1-{3-[(3,5-dichloro-pyridine-4-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-benzoic acid methyl ester (107);
3,5-Dichloro-N-(3-{4-[(4-chloro-phenyl)-(3-cyano-benzyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (108);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-acetylamino-phenyl)-(3-cyano-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (111);
4,6-Dimethyl-pyrimidine-5-carboxylic acid [3-(4-{(3-cyano-benzyl)-[4-(2-methoxy-ethoxy)-phenyl]-amino}-piperidin-1-yl)-butyl]-amide (114);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(3-cyano-benzyl)-(4-hydrazinocarbonylmethoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (116);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(3-cyano-benzyl)-(4-methanesulfonylamino-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (118);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(3-cyano-benzyl)-(4-methoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (119);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(3-cyano-benzyl)-(4-trifluoromethoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (123);
3,5-Dichloro-N-(3-{4-[(3-cyano-benzyl)-(4-methanesulfinyl-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (125);
3,5-Dichloro-N-(3-{4-[(3-cyano-benzyl)-(4-methanesulfonyl-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (126);
3,5-Dichloro-N-(3-{4-[(3-cyano-benzyl)-(4-nitro-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (127);
3,5-Dichloro-N-(3-{4-[(3-cyano-benzyl)-(4-dimethylcarbamoyl-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (128);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(3-cyano-benzyl)-(4-dimethylcarbamoyl-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (129);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(3-cyano-benzyl)-(4-methylcarbamoyl-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (133);
4,6-Dimethyl-pyrimidine-5-carboxylic acid [3-(4-{(3-cyano-benzyl)-[4-(piperazine-1-carbonyl)-phenyl]-amino}-piperidin-1-yl)-butyl]-amide (135);
4,6-Dimethyl-pyrimidine-5-carboxylic acid 4-[(3-cyano-benzyl)-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenyl ester (136);
Acetic acid 4-[(3-cyano-benzyl)-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenyl ester (138);
Carbonic acid 4-[(3-cyano-benzyl)-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenyl ester methyl ester (140);
{4-[(Cyano-benzyl)-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenoxy}-acetic acid tert-butyl ester (144);
Dimethyl-carbamic acid 4-[(3-cyano-benzyl)-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenyl ester (146);
{4-[(3-Cyano-benzyl)-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenoxyl-acetic acid methyl ester (148);
{4-[(3-Cyano-benzyl)-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenoxyl-acetic acid (150);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(3-cyano-benzyl)-(4-methylsulfamoyl-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (152);
4,6-Dimethyl-pyrimidine-5-carboxylic acid [3-(4-{(3-cyano-benzyl)-[4-(cyclopropanecarbonyl-amino)-phenyl]-amino}-piperidin-1-yl)-butyl]-amide (154);
4,6-Dimethyl-pyrimidine-5-carboxylic acid [3-(4-{(3-cyano-benzyl)-[4-(2,2,2-trifluoro-acetylamino)-phenyl]-amino}-piperidin-1-yl)-butyl]-amide (157);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(3-cyano-benzyl)-(4-ureido-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (159);
4,6-Dimethyl-pyrimidine-5-carboxylic acid [3-(4-{(3-cyano-benzyl)-[4-(2-oxo-oxazolidin-3-yl)-phenyl]-amino}-piperidin-1-yl)-butyl]-amide (161);
4-{4-[(3-Cyano-benzyl)-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenoxyl{-benzoic acid (162);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-carbamoyl-phenyl)-(3-cyano-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (164);
4,6-Dimethyl-pyrimidine-5-carboxylic acid [3-(4-{(3-cyano-benzyl)-[4-(morpholine-4-carbonyl)-phenyl]-amino}-piperidin-1-yl)-butyl]-amide (167);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(3-cyano-benzyl}-(4-sulfamoyl-phenyl)-amino]-piperidine-1-yl}-butyl)-amide (168);
Methanesulfonic acid 4-[(3-cyano-benzyl)-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenyl ester (169);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[[4-(acetylamino-methyl)-phenyl]-(3-cyano-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (171);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-acetyl-phenyl)-(3-cyano-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (173);
{4-[(3-Cyano-benzyl)-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-benzoylamino}-acetic acid methyl ester (175);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(3-cyano-benzyl)-(1H-indol-5-yl)-amino]-piperidin-1-yl}-butyl)-amide (178);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[benzo[1,3]dioxol-5-yl-(3-cyano-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (179);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(3-cyano-benzyl)-(2,3-dihydro-benzofuran-5-yl)-amino]-piperidin-1-yl}-butyl)-amide (181);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[benzofuran-5-yl-(3-cyano-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (184);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(3-cyano-benzyl)-(3,4-dimethoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (186);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(3-cyano-benzyl)-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-amino]-piperidin-1-yl}-butyl)-amide (188);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(3-cyano-benzyl)-(6-methoxy-pyridin-3-yl)-amino]-piperidin-1-yl}-butyl)-amide (191);
3,5-Dichloro-N-(3-{4-[(5-chloro-2-fluoro-benzyl)-(4-cyano-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (195);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(5-chloro-2-fluoro-benzyl)-(4-cyano-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (197);
3,5-Dichloro-N-(3-{4-[(5-chloro-2-fluoro-benzyl)-(4-chloro-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (198);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(5-chloro-2-fluoro-benzyl)-(4-dimethylcarbamoyl-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (199);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(5-chloro-2-fluoro-benzyl)-(4-methoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (201);
4,6-Dimethyl-pyrimidine-5-carboxylic acid [3-(4-{(5-chloro-2-fluoro-benzyl)-[4-(2-methoxy-ethoxy)-phenyl]-amino}-piperidin-1-yl)-butyl]-amide (203);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-acetylamino-phenyl)-(5-chloro-2-fluoro-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (205);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-carbamoyl-phenyl)-(5-chloro-2-fluoro-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (207);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(5-chloro-2-fluoro-benzyl)-(4-sulfamoyl-phenyl)-amino]-piperidine-1-yl}-butyl)-amide (209);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-acetyl-phenyl)-(5-chloro-2-fluoro-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (211);
3-[(5-Chloro-2-fluoro-benzyl)-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-benzoic acid methyl ester (2{3);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(5-chloro-2-fluoro-benzyl)-(3-methylcarbamoyl-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (214);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(5-chloro-2-fluoro-benzyl)-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-amino]-piperidin-1-yl}-butyl)-amide (215);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[benzo[1,3]dioxol-5-yl-(5-chloro-2-fluoro-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (218);
3,5-Dichloro-N-(3-{4-[(5-cyano-2-fluoro-benzyl)-(4-cyano-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (219);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(5-cyano-2-fluoro-benzyl)-(4-methoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (221);
4,6-Dimethyl-pyrimidine-5-carboxylic acid [3-(4-{(5-cyano-2-fluoro-benzyl)-[4-(2-methoxy-ethoxy)-phenyl]-amino}-piperidin-1-yl)-butyl]-amide (223);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-acetylamino-phenyl)-(5-cyano-2-fluoro-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (225);
(E)-3-{4-[(5-Cyano-2-fluoro-benzyl)-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenyl 1-acrylic acid methyl ester (227);
4-{4-[(5-Cyano-2-fluoro-benzyl)-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenoxy}-benzoic acid (228);
N-((R)-3-{4-[(5-Cyano-2-fluoro-benzyl)-(4-methoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-3,5-dimethyl-isonicotinamide (230);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-acetyl-phenyl)-(5-cyano-2-fluoro-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (231);
N-((R)-3-{4-[(4-Acetyl-phenyl)-(5-cyano-2-fluoro-benzyl)-amino]-piperidin-1-yl}-butyl)-2,4-dimethyl-nicotinamide (232);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(5-cyano-2-fluoro-benzyl)-(4-hydroxy-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (233);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(5-cyano-2-fluoro-benzyl)-(4-ureido-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (234);
{4-[(5-Cyano-2-fluoro-benzyl)-(1-{(R)-3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenoxy}-acetic acid tert-butyl ester (235);
{4-[(5-Cyano-2-fluoro-benzyl)-(1-{(R)-3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenoxy}-acetic acid methyl ester (237);
{4-[(5-Cyano-2-fluoro-benzyl)-(1-{(R)-3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenoxy}-acetic acid (238); 4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-carbamoylmethoxy-phenyl)-(5-cyano-2-fluoro-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (239);
(E)-3-{4-[(5-Cyano-2-fluoro-benzyl)-(1-{3-[(4,6-dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-amino]-phenyl}-acrylic acid (240);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[benzo[1,3]dioxol-5-yl-(5-cyano-2-fluoro-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (242);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(5-cyano-2-fluoro-benzyl)-(1H-indol-5-yl)-amino]-piperidin-1-yl}-butyl)-amide (245);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(6-acetylamino-pyridin-3-yl)-(5-cyano-2-fluoro-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (246);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-methoxy-phenyl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (290);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[thiophen-3-ylmethyl-(4-trifluoromethoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (291);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-chloro-phenyl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (292);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-acetyl-phenyl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (293);
4,6-Dimethyl-pyrimidine-5-carboxylic acid [(R)-3-(4-{[4-(1-methoxyimino-ethyl)-phenyl]-thiophen-3-ylmethyl-amino}-piperidin-1-yl)-butyl]-amide (294);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[thiophen-3-ylmethyl-(4-trifluoromethyl-phenyl)-amino-piperidin-1-yl}-butyl)-amide (295);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-hydroxy-phenyl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (296);
{4-[(1-{(R)-3-[(4,6-Dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-thiophen-3-ylmethyl-amino]-phenoxy}-acetic acid (297);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-carbamoylmethoxy-phenyl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (298);
4-[(1-{(R)-3-[(4,6-Dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-thiophen-3-ylmethyl-amino]-benzoic acid methyl ester (299);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-carbamoyl-phenyl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (300);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-bromo-phenyl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (301);
4-{4-[(1-{(R)-3-[(4,6-Dimethyl-pyrimidine-5-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-thiophen-3-ylmethyl-amino]-phenoxy}-benzoic acid (302);
4,6-Dimethyl-pyrimidine-5-carboxylic acid [(R)-3-(4-{[4-(4-carbamoyl-phenoxy)-phenyl]-thiophen-3-ylmethyl-amino}-piperidin-1-yl)-butyl]-amide (303);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-fluoro-phenyl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (304);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-ethoxy-phenyl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (305);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-cyano-phenyl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (306);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-methylsulfanyl-phenyl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (307);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-methanesulfonyl-phenyl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (308);
3,5-Dimethyl-N-((R)-3-{4-[thiophen-3-ylmethyl-(4-trifluoromethoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (309);
2,4-Dimethyl-N-((R)-3-{4-[thiophen-3-ylmethyl-(4-trifluoromethoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-nicotinamide (316);
N-((R)-3-{4-[(4-Methoxy-phenyl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-2,4-dimethyl-nicotinamide (321);
3,5-Dichloro-N-((R)-3-{4-[(4-methoxy-phenyl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-isonicotinamide (323);
N-((R)-3-{4-[(4-Methoxy-phenyl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-3,5-dimethyl-isonicotinamide (325);
4,6-Dimethyl-pyrimidine-5-carboxylic acid {3-[4-(pyridin-3-yl-thiophen-3-ylmethyl-amino)-piperidin-1-yl]-butyl}-amide (327);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(6-acetylamino-pyridin-3-yl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (328);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(6-chloro-pyridin-3-yl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (329);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(6-bromo-pyridin-3-yl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (330);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(6-ethoxy-pyridin-3-yl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (331);
2,4-Dimethyl-N-{3-[4-(pyridin-3-yl-thiophen-3-ylmethyl-amino)-piperidin-1-yl]-butyl}-nicotinamide (334);
3,5-Dichloro-N-{3-[4-(pyridin-3-yl-thiophen-3-ylmethyl-amino)-piperidin-1-yl]-butyl}-isonicotinamide (336);
3,5-Dimethyl-N-{3-[4-(pyridin-3-yl-thiophen-3-ylmethyl-amino)-piperidin-1-yl]-butyl}-isonicotinamide (337);
4,6-Dimethyl-pyrimidine-5-carboxylic acid {3-[4-(pyrimidin-5-yl-thiophen-3-ylmethyl-amino)-piperidin-1-yl]-butyl}-amide (339);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-methoxy-phenyl)-(4-methyl-thiophen-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-amide (342);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-bromo-thiophen-3-ylmethyl)-(4-methoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (343);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-methoxy-phenyl)-(4-methoxy-thiophen-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-amide (344);
4,6-Dimethyl-pyrimidine-5-carboxylic acid {(R)-3-[4-(benzo[1,3]dioxol-5-yl-thiophen-3-ylmethyl-amino)-piperidin-1-yl]-butyl}-amide (345);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(2,3-dihydro-benzo[1,4]dioxin-6-yl)-thiophen-3-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (346);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-methoxy-phenyl)-thiophen-2-ylmethyl-amino]-piperidin-1-yl}-butyl)-amide (347);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-methoxy-phenyl)-(3-methyl-thiophen-2-ylmethyl)-amino]-piperidin-1-yl}-butyl)-amide (348);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(5-chloro-thiophen-2-ylmethyl)-(4-methoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (349);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[furan-2-ylmethyl-(4-methoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (350);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-amide (351);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-bromo-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-amide (352);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-methyl-pyridin-3-ylmethyl)-p-tolyl-amino]-piperidin-1-yl}-butyl)-amide (353);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-methyl-pyridin-3-ylmethyl)-(4-methylsulfanyl-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (354);
4,6-Dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-carbamoyl-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-amide (355);
4,6-Dimethyl-pyrimidine-5-carboxylic acid ((R)-3-{4-[(4-methyl-pyridin-3-ylmethyl)-(4-trifluoromethoxy-phenyl)-amino]-piperidin-1-yl}-butyl)-amide (356);
N-(3-{4-[(4-Methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-3,5-dimethyl-isonicotinamide (357);
N-((R)-3-{4-[(4-Methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-2,4-dimethyl-nicotinamide (359);
3,5-Dichloro-N-((R)-3-{4-[(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-isonicotinamide (362);
N-(3-{4-[(4-Carbamoyl-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-2,4-dimethyl-nicotinamide (366);
N-((R)-3 {4-[(4-Carbamoylmethoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-2,4-dimethyl-nicotinamide (367);
Methanesulfonic acid 4-[(1-{(R)-3-[(2,4-dimethyl-pyridine-3-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-(4-methyl-pyridin-3-ylmethyl)-amino]-phenyl ester (368); and
2,4-Dimethyl-N-(3-{4-[(4-methyl-pyridin-3-ylmethyl)-(4-morpholin-4-yl-phenyl)-amino]-piperidin-1-yl}-butyl)-nicotinamide (369).
- A pharmaceutical composition comprising the compound of claim 4 and a pharmaceutically acceptable carrier.
- The compound of claim 1, wherein R3 is indolyl, 1,3-benzodioxolyl, 1,4-benzodioxanyl, or benzofuranyl.
Owners (US)
-
Genzyme Corporation
(Jan 09 2008)
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Anormed Inc
(Aug 15 2005)
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Applicants
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Genzyme Corp
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Inventors
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Zhou Yuanxi
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Bridger Gary J
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Skerlj Renato T
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Bogucki David
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Yang Wen
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Bourque Elyse
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Langille Jonathan
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Li Tong-shuang
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Metz Markus
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Di Fluri Maria R
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Nan Siqiao
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CPC Classifications
-
C07D401/14
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C07D401/12
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C07D413/14
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C07D417/14
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IPC Classifications
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A61K31/4468
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A61K31/4545
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C07D401/12
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C07D401/14
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C07D413/14
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C07D417/14
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Document Preview
- Publication: Feb 17, 2009
-
Application:
Dec 13, 2004
US 1200204 A
-
Priority:
Dec 13, 2004
US 1200204 A
-
Priority:
Dec 11, 2003
US 52897503 P