CA2686951C - Inhibiteurs de diacylglycerol acyltransferase - Google Patents

Inhibiteurs de diacylglycerol acyltransferase Download PDF

Info

Publication number: CA2686951C
Authority: CA; Canada
Prior art keywords: phenyl; trifluoromethyl; amino; carbonyl; compound
Prior art date: 2007-05-22
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA2686951A

Other languages

English (en)

Other versions

CA2686951A1 (fr

Inventor

David Robert Bolin

Adrian Wai-Hing Cheung

Fariborz Firooznia

Matthew Michael Hamilton

Lee Apostle Mcdermott

Yimin Qian

Jenny Tan

Weiya Yun

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Madrigal Pharmaceuticals Inc

Original Assignee

Madrigal Pharmaceuticals Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2007-05-22

Filing date

2008-05-13

Publication date

2016-03-22

2008-05-13 Application filed by Madrigal Pharmaceuticals Inc filed Critical Madrigal Pharmaceuticals Inc

2008-11-27 Publication of CA2686951A1 publication Critical patent/CA2686951A1/fr

2016-03-22 Application granted granted Critical

2016-03-22 Publication of CA2686951C publication Critical patent/CA2686951C/fr

Status Expired - Fee Related legal-status Critical Current

2028-05-13 Anticipated expiration legal-status Critical

Links

108010001348 Diacylglycerol O-acyltransferase Proteins 0.000 title description 4
102000002148 Diacylglycerol O-acyltransferase Human genes 0.000 title description 3
239000002404 acyltransferase inhibitor Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 430
238000011282 treatment Methods 0.000 claims abstract description 16
150000003839 salts Chemical class 0.000 claims abstract description 15
208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 14
208000008589 Obesity Diseases 0.000 claims abstract description 12
235000020824 obesity Nutrition 0.000 claims abstract description 12
208000001145 Metabolic Syndrome Diseases 0.000 claims abstract description 11
201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims abstract description 11
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
238000002360 preparation method Methods 0.000 claims description 738
238000000034 method Methods 0.000 claims description 379
-1 haloloweralkyl Chemical group 0.000 claims description 289
PYCFLCQAJFEELT-UHFFFAOYSA-N 2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C(F)(F)F)=C(C(=O)O)N=C1C1=CC=CC=C1 PYCFLCQAJFEELT-UHFFFAOYSA-N 0.000 claims description 238
125000000217 alkyl group Chemical group 0.000 claims description 180
229910052736 halogen Inorganic materials 0.000 claims description 107
125000001424 substituent group Chemical group 0.000 claims description 104
150000002367 halogens Chemical class 0.000 claims description 101
125000003545 alkoxy group Chemical group 0.000 claims description 61
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 49
125000004093 cyano group Chemical group *C#N 0.000 claims description 48
239000005711 Benzoic acid Substances 0.000 claims description 42
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 39
125000003118 aryl group Chemical group 0.000 claims description 31
238000006243 chemical reaction Methods 0.000 claims description 31
229910052757 nitrogen Inorganic materials 0.000 claims description 31
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 28
239000002253 acid Substances 0.000 claims description 28
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 25
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 14
229910052799 carbon Inorganic materials 0.000 claims description 13
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
125000004122 cyclic group Chemical group 0.000 claims description 13
125000005037 alkyl phenyl group Chemical group 0.000 claims description 12
125000004076 pyridyl group Chemical group 0.000 claims description 11
229910052717 sulfur Inorganic materials 0.000 claims description 11
239000003814 drug Substances 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
125000001072 heteroaryl group Chemical group 0.000 claims description 9
229910052740 iodine Inorganic materials 0.000 claims description 9
208000032928 Dyslipidaemia Diseases 0.000 claims description 8
208000017170 Lipid metabolism disease Diseases 0.000 claims description 8
125000002015 acyclic group Chemical group 0.000 claims description 8
125000004494 ethyl ester group Chemical group 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 7
229910052794 bromium Inorganic materials 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
125000005936 piperidyl group Chemical group 0.000 claims description 6
125000003302 alkenyloxy group Chemical group 0.000 claims description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
150000003973 alkyl amines Chemical class 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
238000011321 prophylaxis Methods 0.000 claims description 4
IBUSLNJQKLZPNR-UHFFFAOYSA-N 2-phenyl-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=CSC(C=2C=CC=CC=2)=N1 IBUSLNJQKLZPNR-UHFFFAOYSA-N 0.000 claims description 3
DWXWRKKMEWHHFT-UHFFFAOYSA-N 4-[4-[4-[[1-(4-fluorophenyl)-3-(trifluoromethyl)pyrazole-4-carbonyl]amino]phenyl]piperidine-1-carbonyl]cyclohexane-1-carboxylic acid Chemical compound C1CC(C(=O)O)CCC1C(=O)N1CCC(C=2C=CC(NC(=O)C=3C(=NN(C=3)C=3C=CC(F)=CC=3)C(F)(F)F)=CC=2)CC1 DWXWRKKMEWHHFT-UHFFFAOYSA-N 0.000 claims description 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
RHRJDXCKSLXRPS-AWEZNQCLSA-N ethyl (3s)-3-[[5-[[2-[2-(trifluoromethoxy)phenyl]-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CC[C@@H]1NC(N=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C(=CC=CC=2)OC(F)(F)F)=N1 RHRJDXCKSLXRPS-AWEZNQCLSA-N 0.000 claims description 3
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
239000013543 active substance Substances 0.000 claims description 2
IVFZDFSUDXLBMT-SFHVURJKSA-N ethyl (3s)-3-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]anilino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CC[C@@H]1NC(C=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 IVFZDFSUDXLBMT-SFHVURJKSA-N 0.000 claims description 2
QRJBYYPWKFKHDT-UHFFFAOYSA-N ethyl 1-[1-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-4-carbonyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(=O)C1CCN(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 QRJBYYPWKFKHDT-UHFFFAOYSA-N 0.000 claims description 2
125000001188 haloalkyl group Chemical group 0.000 claims description 2
BKYNFPVUIIEGBZ-UHFFFAOYSA-N methyl 1-[1-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-4-carbonyl]pyrrolidine-3-carboxylate Chemical compound C1C(C(=O)OC)CCN1C(=O)C1CCN(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 BKYNFPVUIIEGBZ-UHFFFAOYSA-N 0.000 claims description 2
125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
FNXJXLPVHMZFFE-UHFFFAOYSA-N 2,2-dimethyl-3-[1-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]piperidin-4-yl]propanoic acid Chemical compound C1CC(CC(C)(C)C(O)=O)CCN1C(N=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 FNXJXLPVHMZFFE-UHFFFAOYSA-N 0.000 claims 3
BHGWBRJSNXDLFG-NHCUHLMSSA-N (1r,2r)-2-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperazine-1-carbonyl]cyclopentane-1-carboxylic acid Chemical compound OC(=O)[C@@H]1CCC[C@H]1C(=O)N1CCN(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 BHGWBRJSNXDLFG-NHCUHLMSSA-N 0.000 claims 2
RETWODQJPUEKGV-DHIUTWEWSA-N (1r,2r)-2-[[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]phenyl]carbamoyl]cyclopentane-1-carboxylic acid Chemical compound OC(=O)[C@@H]1CCC[C@H]1C(=O)NC1=CC=C(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)C=C1 RETWODQJPUEKGV-DHIUTWEWSA-N 0.000 claims 2
IRUXIWCQYXLNGQ-DHIUTWEWSA-N (1r,2r)-2-[methyl-[1-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidin-4-yl]carbamoyl]cyclopentane-1-carboxylic acid Chemical compound O=C([C@H]1[C@@H](CCC1)C(O)=O)N(C)C(CC1)CCN1C(C=C1)=CC=C1NC(=O)C(=C(O1)C(F)(F)F)N=C1C1=CC=CC=C1 IRUXIWCQYXLNGQ-DHIUTWEWSA-N 0.000 claims 2
RETWODQJPUEKGV-GOTSBHOMSA-N (1s,2s)-2-[[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]phenyl]carbamoyl]cyclopentane-1-carboxylic acid Chemical compound OC(=O)[C@H]1CCC[C@@H]1C(=O)NC1=CC=C(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)C=C1 RETWODQJPUEKGV-GOTSBHOMSA-N 0.000 claims 2
MLSMPYMKZFXVAV-UHFFFAOYSA-N 2,2-dimethyl-4-[methyl-[1-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidin-4-yl]amino]-4-oxobutanoic acid Chemical compound C1CC(N(C)C(=O)CC(C)(C)C(O)=O)CCN1C(C=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 MLSMPYMKZFXVAV-UHFFFAOYSA-N 0.000 claims 2
IQAQKXBLIKEPKV-UHFFFAOYSA-N 2-[1-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-1-carbonyl]piperidin-4-yl]acetic acid Chemical compound C1CC(CC(=O)O)CCN1C(=O)N1CCC(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 IQAQKXBLIKEPKV-UHFFFAOYSA-N 0.000 claims 2
ONKPRMYOGAJGFB-UHFFFAOYSA-N 2-phenyl-n-[4-[1-[4-(2h-tetrazol-5-yl)cyclohexanecarbonyl]piperidin-4-yl]phenyl]-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound FC(F)(F)C=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=C1)=CC=C1C(CC1)CCN1C(=O)C(CC1)CCC1C1=NN=NN1 ONKPRMYOGAJGFB-UHFFFAOYSA-N 0.000 claims 2
CTWKCOVVBDPRFE-UHFFFAOYSA-N 3-chloro-4-[5-[[1-(4-fluorophenyl)-3-(trifluoromethyl)pyrazole-4-carbonyl]amino]pyridin-2-yl]benzoic acid Chemical compound ClC1=CC(C(=O)O)=CC=C1C(N=C1)=CC=C1NC(=O)C1=CN(C=2C=CC(F)=CC=2)N=C1C(F)(F)F CTWKCOVVBDPRFE-UHFFFAOYSA-N 0.000 claims 2
LZBFHPFSNBDUBK-UHFFFAOYSA-N 4-[4-[(5-methyl-2-phenyltriazole-4-carbonyl)amino]phenyl]-n-propylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)NCCC)CCC1C(C=C1)=CC=C1NC(=O)C1=NN(C=2C=CC=CC=2)N=C1C LZBFHPFSNBDUBK-UHFFFAOYSA-N 0.000 claims 2
IGJJXZYULQEUJD-UHFFFAOYSA-N 4-[4-[[1-(4-fluorophenyl)-3-(trifluoromethyl)pyrazole-4-carbonyl]amino]phenyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(C=C1)=CC=C1NC(=O)C1=CN(C=2C=CC(F)=CC=2)N=C1C(F)(F)F IGJJXZYULQEUJD-UHFFFAOYSA-N 0.000 claims 2
DELPAORSALAKTH-UHFFFAOYSA-N 4-[5-[[1-(4-fluorophenyl)-3-(trifluoromethyl)pyrazole-4-carbonyl]amino]pyridin-2-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(N=C1)=CC=C1NC(=O)C1=CN(C=2C=CC(F)=CC=2)N=C1C(F)(F)F DELPAORSALAKTH-UHFFFAOYSA-N 0.000 claims 2
FTOWPSVZIQKJEJ-SFHVURJKSA-N ethyl (3s)-3-[4-[[1-phenyl-3-(trifluoromethyl)pyrazole-4-carbonyl]amino]anilino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CC[C@@H]1NC(C=C1)=CC=C1NC(=O)C1=CN(C=2C=CC=CC=2)N=C1C(F)(F)F FTOWPSVZIQKJEJ-SFHVURJKSA-N 0.000 claims 2
UPXRSMSKXOEFEF-INIZCTEOSA-N ethyl (3s)-3-[4-[[2-[2-(trifluoromethoxy)phenyl]-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]anilino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CC[C@@H]1NC(C=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C(=CC=CC=2)OC(F)(F)F)=N1 UPXRSMSKXOEFEF-INIZCTEOSA-N 0.000 claims 2
AXKLANROCSVOMM-INIZCTEOSA-N ethyl (3s)-3-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]oxypyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CC[C@@H]1OC(N=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 AXKLANROCSVOMM-INIZCTEOSA-N 0.000 claims 2
IRKYZZXDYNWXDY-INIZCTEOSA-N ethyl (3s)-3-[[5-[(4-methyl-2-pyridin-2-yl-1,3-thiazole-5-carbonyl)amino]pyridin-2-yl]amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CC[C@@H]1NC(N=C1)=CC=C1NC(=O)C1=C(C)N=C(C=2N=CC=CC=2)S1 IRKYZZXDYNWXDY-INIZCTEOSA-N 0.000 claims 2
XVBHEADJSSBWDF-INIZCTEOSA-N ethyl (3s)-3-[[5-[[1-phenyl-3-(trifluoromethyl)pyrazole-4-carbonyl]amino]pyridin-2-yl]amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CC[C@@H]1NC(N=C1)=CC=C1NC(=O)C1=CN(C=2C=CC=CC=2)N=C1C(F)(F)F XVBHEADJSSBWDF-INIZCTEOSA-N 0.000 claims 2
BOKLCWCZYGJQQW-UHFFFAOYSA-N n-[4-[1-(cyclopentanecarbonyl)piperidin-4-yl]phenyl]-1-pyridin-2-yl-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound FC(F)(F)C1=NN(C=2N=CC=CC=2)C=C1C(=O)NC(C=C1)=CC=C1C(CC1)CCN1C(=O)C1CCCC1 BOKLCWCZYGJQQW-UHFFFAOYSA-N 0.000 claims 2
GBNVKPMJEJJLBQ-UHFFFAOYSA-N n-[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]phenyl]-1-pyridin-2-yl-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound FC(F)(F)C1=NN(C=2N=CC=CC=2)C=C1C(=O)NC(C=C1)=CC=C1C(CC1)CCN1C(=O)C1CC1 GBNVKPMJEJJLBQ-UHFFFAOYSA-N 0.000 claims 2
BZPQWHMYFUNVLX-UHFFFAOYSA-N n-[4-[1-[3-(3-oxo-1,2-oxazol-5-yl)propanoyl]piperidin-4-yl]phenyl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound O1N=C(O)C=C1CCC(=O)N1CCC(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 BZPQWHMYFUNVLX-UHFFFAOYSA-N 0.000 claims 2
OWXPOEKTJJCSCC-UHFFFAOYSA-N n-[4-[1-[4-(5-oxo-2h-1,2,4-oxadiazol-3-yl)cyclohexanecarbonyl]piperidin-4-yl]phenyl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound FC(F)(F)C=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=C1)=CC=C1C(CC1)CCN1C(=O)C(CC1)CCC1C1=NOC(=O)N1 OWXPOEKTJJCSCC-UHFFFAOYSA-N 0.000 claims 2
KQCIWGUAUKBWQH-UHFFFAOYSA-N n-[6-[4-(2-methylpropylcarbamoyl)phenyl]pyridin-3-yl]-2-pyridin-2-yl-4-(trifluoromethyl)-1,3-oxazole-5-carboxamide Chemical compound C1=CC(C(=O)NCC(C)C)=CC=C1C(N=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)N=C(C=2N=CC=CC=2)O1 KQCIWGUAUKBWQH-UHFFFAOYSA-N 0.000 claims 2
BAICKYASNINPIW-KRWDZBQOSA-N n-[6-[[(3s)-1-(2-methylpropanoyl)pyrrolidin-3-yl]amino]pyridin-3-yl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound C1N(C(=O)C(C)C)CC[C@@H]1NC(N=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 BAICKYASNINPIW-KRWDZBQOSA-N 0.000 claims 2
ILCYOKOPSGDYJR-KRWDZBQOSA-N tert-butyl (3s)-3-[[5-[(4-methyl-2-pyridin-2-yl-1,3-thiazole-5-carbonyl)amino]pyridin-2-yl]amino]pyrrolidine-1-carboxylate Chemical compound CC=1N=C(C=2N=CC=CC=2)SC=1C(=O)NC(C=N1)=CC=C1N[C@H]1CCN(C(=O)OC(C)(C)C)C1 ILCYOKOPSGDYJR-KRWDZBQOSA-N 0.000 claims 2
ORLMEMWKGCGHPA-PWRODBHTSA-N (1r,2r)-2-[(3s)-3-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenoxy]pyrrolidine-1-carbonyl]cyclopentane-1-carboxylic acid Chemical compound OC(=O)[C@@H]1CCC[C@H]1C(=O)N1C[C@@H](OC=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 ORLMEMWKGCGHPA-PWRODBHTSA-N 0.000 claims 1
YADSXGYUJIXCIC-FGZHOGPDSA-N (1r,2r)-2-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-1-carbonyl]cyclopentane-1-carboxylic acid Chemical compound OC(=O)[C@@H]1CCC[C@H]1C(=O)N1CCC(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 YADSXGYUJIXCIC-FGZHOGPDSA-N 0.000 claims 1
KHPYEYGHDMAMGD-VQTJNVASSA-N (1r,3s)-3-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperazine-1-carbonyl]cyclohexane-1-carboxylic acid Chemical compound C1[C@H](C(=O)O)CCC[C@@H]1C(=O)N1CCN(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 KHPYEYGHDMAMGD-VQTJNVASSA-N 0.000 claims 1
JULHREJWLLNGNJ-OALUTQOASA-N (1s,2s)-2-[4-[3-fluoro-4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperazine-1-carbonyl]cyclopentane-1-carboxylic acid Chemical compound OC(=O)[C@H]1CCC[C@@H]1C(=O)N1CCN(C=2C=C(F)C(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 JULHREJWLLNGNJ-OALUTQOASA-N 0.000 claims 1
CFYHCSHUIUTQMI-PMACEKPBSA-N (1s,2s)-2-[4-[4-[(2-tert-butyl-5-methyl-1,3-oxazole-4-carbonyl)amino]phenyl]piperazine-1-carbonyl]cyclopentane-1-carboxylic acid Chemical compound O1C(C(C)(C)C)=NC(C(=O)NC=2C=CC(=CC=2)N2CCN(CC2)C(=O)[C@@H]2[C@H](CCC2)C(O)=O)=C1C CFYHCSHUIUTQMI-PMACEKPBSA-N 0.000 claims 1
IRUXIWCQYXLNGQ-GOTSBHOMSA-N (1s,2s)-2-[methyl-[1-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidin-4-yl]carbamoyl]cyclopentane-1-carboxylic acid Chemical compound O=C([C@@H]1[C@H](CCC1)C(O)=O)N(C)C(CC1)CCN1C(C=C1)=CC=C1NC(=O)C(=C(O1)C(F)(F)F)N=C1C1=CC=CC=C1 IRUXIWCQYXLNGQ-GOTSBHOMSA-N 0.000 claims 1
SKEDTYBNNNNCEN-SFTDATJTSA-N (1s,2s)-2-[methyl-[1-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]piperidin-4-yl]carbamoyl]cyclopentane-1-carboxylic acid Chemical compound O=C([C@@H]1[C@H](CCC1)C(O)=O)N(C)C(CC1)CCN1C(N=C1)=CC=C1NC(=O)C(=C(O1)C(F)(F)F)N=C1C1=CC=CC=C1 SKEDTYBNNNNCEN-SFTDATJTSA-N 0.000 claims 1
LGGJIXXQVDIZAQ-NRFANRHFSA-N (2s)-1-[1-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-4-carbonyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)C1CCN(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 LGGJIXXQVDIZAQ-NRFANRHFSA-N 0.000 claims 1
OBLCSYZBGDZBJP-UHFFFAOYSA-N 1-[1-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-4-carbonyl]piperidine-2-carboxylic acid Chemical compound OC(=O)C1CCCCN1C(=O)C1CCN(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 OBLCSYZBGDZBJP-UHFFFAOYSA-N 0.000 claims 1
FOCRLNXSIIYKET-UHFFFAOYSA-N 1-[1-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-4-carbonyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C(=O)C1CCN(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 FOCRLNXSIIYKET-UHFFFAOYSA-N 0.000 claims 1
QXRQNAYWTZDAJC-UHFFFAOYSA-N 1-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-1-carbonyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C(=O)N1CCC(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 QXRQNAYWTZDAJC-UHFFFAOYSA-N 0.000 claims 1
QKHYUDIFFVTCDE-UHFFFAOYSA-N 1-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-1-carbonyl]pyrrolidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CCN1C(=O)N1CCC(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 QKHYUDIFFVTCDE-UHFFFAOYSA-N 0.000 claims 1
VGBXWWKNVODDTJ-UHFFFAOYSA-N 1-methyl-4-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-1-carbonyl]cyclohexane-1-carboxylic acid Chemical compound C1CC(C)(C(O)=O)CCC1C(=O)N1CCC(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 VGBXWWKNVODDTJ-UHFFFAOYSA-N 0.000 claims 1
RMIRLOXABJGUJO-UHFFFAOYSA-N 2,2-dimethyl-4-[4-[4-[(5-methyl-2-phenyl-1,3-oxazole-4-carbonyl)amino]phenyl]piperidin-1-yl]-4-oxobutanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=C1)=CC=C1C1CCN(C(=O)CC(C)(C)C(O)=O)CC1 RMIRLOXABJGUJO-UHFFFAOYSA-N 0.000 claims 1
OZVGIYSTVUWMGB-UHFFFAOYSA-N 2,2-dimethyl-4-oxo-4-[3-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenoxy]piperidin-1-yl]butanoic acid Chemical compound C1N(C(=O)CC(C)(C)C(O)=O)CCCC1OC(C=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 OZVGIYSTVUWMGB-UHFFFAOYSA-N 0.000 claims 1
VRAMGYCGTBTZDN-UHFFFAOYSA-N 2,2-dimethyl-4-oxo-4-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]phenyl]butanoic acid Chemical compound C1=CC(C(=O)CC(C)(C)C(O)=O)=CC=C1C(C=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 VRAMGYCGTBTZDN-UHFFFAOYSA-N 0.000 claims 1
WGKCAVKDCBRORD-UHFFFAOYSA-N 2,2-dimethyl-4-oxo-4-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperazin-1-yl]butanoic acid Chemical compound C1CN(C(=O)CC(C)(C)C(O)=O)CCN1C(C=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 WGKCAVKDCBRORD-UHFFFAOYSA-N 0.000 claims 1
ANLAQQSXCLJGRW-UHFFFAOYSA-N 2,2-dimethyl-5-oxo-5-[3-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenoxy]piperidin-1-yl]pentanoic acid Chemical compound C1N(C(=O)CCC(C)(C)C(O)=O)CCCC1OC(C=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 ANLAQQSXCLJGRW-UHFFFAOYSA-N 0.000 claims 1
RIPZRLRAXYJCPL-UHFFFAOYSA-N 2-[4-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]benzoyl]cyclopentane-1-carboxylic acid Chemical compound OC(=O)C1CCCC1C(=O)C1=CC=C(C=2N=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)C=C1 RIPZRLRAXYJCPL-UHFFFAOYSA-N 0.000 claims 1
OQPICJMUEMCDQR-UHFFFAOYSA-N 2-phenyl-n-[4-[1-[2-(2h-tetrazol-5-yl)acetyl]piperidin-4-yl]phenyl]-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound FC(F)(F)C=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=C1)=CC=C1C(CC1)CCN1C(=O)CC1=NN=NN1 OQPICJMUEMCDQR-UHFFFAOYSA-N 0.000 claims 1
YLVKUJRITASIAX-UHFFFAOYSA-N 2-phenyl-n-[4-[4-[2-(2h-tetrazol-5-yl)acetyl]piperazin-1-yl]phenyl]-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound FC(F)(F)C=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=C1)=CC=C1N(CC1)CCN1C(=O)CC1=NN=NN1 YLVKUJRITASIAX-UHFFFAOYSA-N 0.000 claims 1
GHCOMEFFFZBWOP-UHFFFAOYSA-N 2-phenyl-n-[4-[4-[4-(2h-tetrazol-5-yl)cyclohexanecarbonyl]piperazin-1-yl]phenyl]-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound FC(F)(F)C=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=C1)=CC=C1N(CC1)CCN1C(=O)C(CC1)CCC1C1=NN=NN1 GHCOMEFFFZBWOP-UHFFFAOYSA-N 0.000 claims 1
DFQRAVSDALGQGI-UHFFFAOYSA-N 3,3-dimethyl-5-oxo-5-[3-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenoxy]piperidin-1-yl]pentanoic acid Chemical compound C1N(C(=O)CC(C)(CC(O)=O)C)CCCC1OC(C=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 DFQRAVSDALGQGI-UHFFFAOYSA-N 0.000 claims 1
KRFDMWHAUBHOHF-UHFFFAOYSA-N 3-[1-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-1-carbonyl]piperidin-4-yl]propanoic acid Chemical compound C1CC(CCC(=O)O)CCN1C(=O)N1CCC(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 KRFDMWHAUBHOHF-UHFFFAOYSA-N 0.000 claims 1
WTJPFPNGRRCRMQ-UHFFFAOYSA-N 3-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperazine-1-carbonyl]adamantane-1-carboxylic acid Chemical compound C1C(C(=O)O)(C2)CC(C3)CC1CC32C(=O)N(CC1)CCN1C(C=C1)=CC=C1NC(=O)C(=C(O1)C(F)(F)F)N=C1C1=CC=CC=C1 WTJPFPNGRRCRMQ-UHFFFAOYSA-N 0.000 claims 1
VINZJTPYWRACGA-UHFFFAOYSA-N 4-[1-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-1-carbonyl]piperidin-4-yl]butanoic acid Chemical compound C1CC(CCCC(=O)O)CCN1C(=O)N1CCC(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 VINZJTPYWRACGA-UHFFFAOYSA-N 0.000 claims 1
MARFUFVBECBSBC-UHFFFAOYSA-N 4-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-1-carbonyl]cyclohexane-1-carboxylic acid Chemical compound C1CC(C(=O)O)CCC1C(=O)N1CCC(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 MARFUFVBECBSBC-UHFFFAOYSA-N 0.000 claims 1
KMNYYEXPRMKYIH-WGSAOQKQSA-N C1C[C@@H](C(=O)O)CC[C@@H]1C(=O)N1CCN(C=2C=C(F)C(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 Chemical compound C1C[C@@H](C(=O)O)CC[C@@H]1C(=O)N1CCN(C=2C=C(F)C(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 KMNYYEXPRMKYIH-WGSAOQKQSA-N 0.000 claims 1
HTRVUVYQDBIUPI-IPJJNNNSSA-N C1C[C@@H](C(=O)O)CC[C@@H]1C(=O)N1C[C@@H](OC=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 Chemical compound C1C[C@@H](C(=O)O)CC[C@@H]1C(=O)N1C[C@@H](OC=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 HTRVUVYQDBIUPI-IPJJNNNSSA-N 0.000 claims 1
LEHBYBLXUUUJMC-MXVIHJGJSA-N chembl1766809 Chemical compound C1C[C@@H](C(=O)O)CC[C@@H]1C(=O)N1CCN(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 LEHBYBLXUUUJMC-MXVIHJGJSA-N 0.000 claims 1
NFQPFDYSKZBOSQ-OAHLLOKOSA-N ethyl (3r)-3-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyrimidin-2-yl]oxypyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CC[C@H]1OC(N=C1)=NC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 NFQPFDYSKZBOSQ-OAHLLOKOSA-N 0.000 claims 1
VPIIMEKIVFENNY-IBGZPJMESA-N ethyl (3s)-3-[4-[[1-phenyl-3-(trifluoromethyl)pyrazole-4-carbonyl]amino]phenoxy]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CC[C@@H]1OC(C=C1)=CC=C1NC(=O)C1=CN(C=2C=CC=CC=2)N=C1C(F)(F)F VPIIMEKIVFENNY-IBGZPJMESA-N 0.000 claims 1
CWWGBHGRZCJETK-ZDUSSCGKSA-N ethyl (3s)-3-[5-[[2-[2-(trifluoromethoxy)phenyl]-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyrimidin-2-yl]oxypyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CC[C@@H]1OC(N=C1)=NC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C(=CC=CC=2)OC(F)(F)F)=N1 CWWGBHGRZCJETK-ZDUSSCGKSA-N 0.000 claims 1
LTEQUEBGLIACNY-HNNXBMFYSA-N ethyl (3s)-3-[[5-[[1-pyridin-2-yl-3-(trifluoromethyl)pyrazole-4-carbonyl]amino]pyridin-2-yl]amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CC[C@@H]1NC(N=C1)=CC=C1NC(=O)C1=CN(C=2N=CC=CC=2)N=C1C(F)(F)F LTEQUEBGLIACNY-HNNXBMFYSA-N 0.000 claims 1
HWCWBRQJWLFCOA-LBPRGKRZSA-N ethyl (3s)-3-[[5-[[2-[2-(trifluoromethoxy)phenyl]-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyrimidin-2-yl]amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CC[C@@H]1NC(N=C1)=NC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C(=CC=CC=2)OC(F)(F)F)=N1 HWCWBRQJWLFCOA-LBPRGKRZSA-N 0.000 claims 1
CDLAYOMPYNNCQK-UHFFFAOYSA-N ethyl 1-[1-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-4-carbonyl]piperidine-3-carboxylate Chemical compound C1C(C(=O)OCC)CCCN1C(=O)C1CCN(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 CDLAYOMPYNNCQK-UHFFFAOYSA-N 0.000 claims 1
QLNCSQFFTAILSQ-UHFFFAOYSA-N ethyl 3-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]oxypiperidine-1-carboxylate Chemical compound C1N(C(=O)OCC)CCCC1OC(N=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 QLNCSQFFTAILSQ-UHFFFAOYSA-N 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
PLZSQXRTQFNNIY-QFIPXVFZSA-N methyl (2s)-1-[1-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-4-carbonyl]pyrrolidine-2-carboxylate Chemical compound COC(=O)[C@@H]1CCCN1C(=O)C1CCN(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 PLZSQXRTQFNNIY-QFIPXVFZSA-N 0.000 claims 1
FFDAGFYGPGJOOG-UHFFFAOYSA-N methyl 2-[4-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]benzoyl]cyclopentane-1-carboxylate Chemical compound COC(=O)C1CCCC1C(=O)C1=CC=C(C=2N=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)C=C1 FFDAGFYGPGJOOG-UHFFFAOYSA-N 0.000 claims 1
RTEFVLXCSZGXDA-UHFFFAOYSA-N n-[4-[1-[2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetyl]piperidin-4-yl]phenyl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound FC(F)(F)C=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=C1)=CC=C1C(CC1)CCN1C(=O)CC1SC(=O)NC1=O RTEFVLXCSZGXDA-UHFFFAOYSA-N 0.000 claims 1
NYUCPOIFVHRXGO-UHFFFAOYSA-N n-[4-[4-(tert-butylsulfonylcarbamoyl)piperidin-1-yl]phenyl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound C1CC(C(=O)NS(=O)(=O)C(C)(C)C)CCN1C(C=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 NYUCPOIFVHRXGO-UHFFFAOYSA-N 0.000 claims 1
XKMXHTIZXOSTNE-JOCHJYFZSA-N n-[4-[4-[(2r)-1-(dimethylsulfamoyl)pyrrolidine-2-carbonyl]piperazin-1-yl]phenyl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound CN(C)S(=O)(=O)N1CCC[C@@H]1C(=O)N1CCN(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 XKMXHTIZXOSTNE-JOCHJYFZSA-N 0.000 claims 1
NVLNLLFCIDZRGP-OAQYLSRUSA-N n-[4-[4-[(2r)-1-methylsulfonylpyrrolidine-2-carbonyl]piperazin-1-yl]phenyl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound CS(=O)(=O)N1CCC[C@@H]1C(=O)N1CCN(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 NVLNLLFCIDZRGP-OAQYLSRUSA-N 0.000 claims 1
XKMXHTIZXOSTNE-QFIPXVFZSA-N n-[4-[4-[(2s)-1-(dimethylsulfamoyl)pyrrolidine-2-carbonyl]piperazin-1-yl]phenyl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound CN(C)S(=O)(=O)N1CCC[C@H]1C(=O)N1CCN(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 XKMXHTIZXOSTNE-QFIPXVFZSA-N 0.000 claims 1
NVLNLLFCIDZRGP-NRFANRHFSA-N n-[4-[4-[(2s)-1-methylsulfonylpyrrolidine-2-carbonyl]piperazin-1-yl]phenyl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound CS(=O)(=O)N1CCC[C@H]1C(=O)N1CCN(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 NVLNLLFCIDZRGP-NRFANRHFSA-N 0.000 claims 1
PPVCSDBNQCVWCS-UHFFFAOYSA-N n-[4-[4-[2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetyl]piperazin-1-yl]phenyl]-2-phenyl-1,3-thiazole-4-carboxamide Chemical compound C1CN(C=2C=CC(NC(=O)C=3N=C(SC=3)C=3C=CC=CC=3)=CC=2)CCN1C(=O)CC1SC(=O)NC1=O PPVCSDBNQCVWCS-UHFFFAOYSA-N 0.000 claims 1
DUJKGNOCXCLVGJ-UHFFFAOYSA-N n-[4-[4-[ethylcarbamoyl(methyl)amino]piperidin-1-yl]phenyl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound C1CC(N(C)C(=O)NCC)CCN1C(C=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 DUJKGNOCXCLVGJ-UHFFFAOYSA-N 0.000 claims 1
SJSDCZCLTJGBPX-UHFFFAOYSA-N n-[4-[4-[methyl(propylcarbamoyl)amino]piperidin-1-yl]phenyl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound C1CC(N(C)C(=O)NCCC)CCN1C(C=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 SJSDCZCLTJGBPX-UHFFFAOYSA-N 0.000 claims 1
LDWHSEFQCJLJJX-UHFFFAOYSA-N n-[6-(4-carbamoylpiperidin-1-yl)pyridin-3-yl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound C1CC(C(=O)N)CCN1C(N=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 LDWHSEFQCJLJJX-UHFFFAOYSA-N 0.000 claims 1
NPBLVMMQWPQOGP-UHFFFAOYSA-N n-[6-[4-(cyclopropylcarbamoyl)phenyl]pyridin-3-yl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound FC(F)(F)C=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=N1)=CC=C1C(C=C1)=CC=C1C(=O)NC1CC1 NPBLVMMQWPQOGP-UHFFFAOYSA-N 0.000 claims 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
201000010099 disease Diseases 0.000 abstract description 4
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 334
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 262
239000000203 mixture Substances 0.000 description 153
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238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 102
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239000007787 solid Substances 0.000 description 84
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
239000002904 solvent Substances 0.000 description 54
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 51
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 45
239000012044 organic layer Substances 0.000 description 44
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238000012360 testing method Methods 0.000 description 2
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150000003672 ureas Chemical class 0.000 description 2
238000010626 work up procedure Methods 0.000 description 2
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WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
239000012453 solvate Substances 0.000 description 1
238000007614 solvation Methods 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000003860 storage Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000005017 substituted alkenyl group Chemical group 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
125000004426 substituted alkynyl group Chemical group 0.000 description 1
125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
150000003457 sulfones Chemical group 0.000 description 1
150000003462 sulfoxides Chemical group 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
239000003826 tablet Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
IUUYANMOEMBTBV-OGFXRTJISA-N tert-butyl (2r)-pyrrolidine-2-carboxylate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)[C@H]1CCCN1 IUUYANMOEMBTBV-OGFXRTJISA-N 0.000 description 1
IGZORTGLYQDNMF-SSDOTTSWSA-N tert-butyl (2s)-2-amino-3,3-dimethylbutanoate Chemical compound CC(C)(C)OC(=O)[C@@H](N)C(C)(C)C IGZORTGLYQDNMF-SSDOTTSWSA-N 0.000 description 1
XJJBXZIKXFOMLP-ZETCQYMHSA-N tert-butyl (2s)-pyrrolidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1CCCN1 XJJBXZIKXFOMLP-ZETCQYMHSA-N 0.000 description 1
PFYOFRHEJVHCND-LLVKDONJSA-N tert-butyl (3r)-3-[(5-aminopyridin-2-yl)amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@H]1NC1=CC=C(N)C=N1 PFYOFRHEJVHCND-LLVKDONJSA-N 0.000 description 1
RAYFFVQMYZRSEO-SNVBAGLBSA-N tert-butyl (3r)-3-[(5-nitropyridin-2-yl)amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@H]1NC1=CC=C([N+]([O-])=O)C=N1 RAYFFVQMYZRSEO-SNVBAGLBSA-N 0.000 description 1
IXETXAKEWMYRQI-QGZVFWFLSA-N tert-butyl (3r)-3-[[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@H]1NC(N=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 IXETXAKEWMYRQI-QGZVFWFLSA-N 0.000 description 1
CMIBWIAICVBURI-SSDOTTSWSA-N tert-butyl (3r)-3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](N)C1 CMIBWIAICVBURI-SSDOTTSWSA-N 0.000 description 1
RYWQNZFJMSYAED-ZDUSSCGKSA-N tert-butyl (3s)-3-(4-aminophenoxy)pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1OC1=CC=C(N)C=C1 RYWQNZFJMSYAED-ZDUSSCGKSA-N 0.000 description 1
SGQPXIZHVCLLRP-ZDUSSCGKSA-N tert-butyl (3s)-3-(4-nitrophenoxy)pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1OC1=CC=C([N+]([O-])=O)C=C1 SGQPXIZHVCLLRP-ZDUSSCGKSA-N 0.000 description 1
PRDVDKXXIRYCAA-NSHDSACASA-N tert-butyl (3s)-3-(5-aminopyridin-2-yl)oxypyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1OC1=CC=C(N)C=N1 PRDVDKXXIRYCAA-NSHDSACASA-N 0.000 description 1
DIGLAIRFOUGIMZ-JTQLQIEISA-N tert-butyl (3s)-3-(5-nitropyrimidin-2-yl)oxypyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1OC1=NC=C([N+]([O-])=O)C=N1 DIGLAIRFOUGIMZ-JTQLQIEISA-N 0.000 description 1
GHVCZCDORVILFB-VIFPVBQESA-N tert-butyl (3s)-3-[(5-nitropyrimidin-2-yl)amino]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1NC1=NC=C([N+]([O-])=O)C=N1 GHVCZCDORVILFB-VIFPVBQESA-N 0.000 description 1
CMIBWIAICVBURI-UHFFFAOYSA-N tert-butyl 3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)C1 CMIBWIAICVBURI-UHFFFAOYSA-N 0.000 description 1
UIJXHKXIOCDSEB-UHFFFAOYSA-N tert-butyl 3-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(O)C1 UIJXHKXIOCDSEB-UHFFFAOYSA-N 0.000 description 1
RXFHRKPNLPBDGE-UHFFFAOYSA-N tert-butyl 4-(4-aminophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(N)C=C1 RXFHRKPNLPBDGE-UHFFFAOYSA-N 0.000 description 1
UNNMTKGKCWNQNU-UHFFFAOYSA-N tert-butyl 4-(4-nitrophenoxy)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OC1=CC=C([N+]([O-])=O)C=C1 UNNMTKGKCWNQNU-UHFFFAOYSA-N 0.000 description 1
MGYCIJUTYLUYJM-UHFFFAOYSA-N tert-butyl 4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C([N+]([O-])=O)C=C1 MGYCIJUTYLUYJM-UHFFFAOYSA-N 0.000 description 1
PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
FEYLUKDSKVSMSZ-UHFFFAOYSA-N tert-butyl n-(4-aminocyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(N)CC1 FEYLUKDSKVSMSZ-UHFFFAOYSA-N 0.000 description 1
NSOGPQYEDHRIBD-SNVBAGLBSA-N tert-butyl n-[(3r)-1-[(5-aminopyrimidin-2-yl)amino]pyrrolidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCN1NC1=NC=C(N)C=N1 NSOGPQYEDHRIBD-SNVBAGLBSA-N 0.000 description 1
DQQJBEAXSOOCPG-SSDOTTSWSA-N tert-butyl n-[(3r)-pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCNC1 DQQJBEAXSOOCPG-SSDOTTSWSA-N 0.000 description 1
DQQJBEAXSOOCPG-ZETCQYMHSA-N tert-butyl n-[(3s)-pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CCNC1 DQQJBEAXSOOCPG-ZETCQYMHSA-N 0.000 description 1
FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
SIPCWZPMFWUPID-UHFFFAOYSA-N tert-butyl n-[4-(4-aminoanilino)cyclohexyl]carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCC1NC1=CC=C(N)C=C1 SIPCWZPMFWUPID-UHFFFAOYSA-N 0.000 description 1
USZVCDRKIVKICD-UHFFFAOYSA-N tert-butyl n-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]carbamate Chemical compound C1=NC(NC(=O)OC(C)(C)C)=CC=C1B1OC(C)(C)C(C)(C)O1 USZVCDRKIVKICD-UHFFFAOYSA-N 0.000 description 1
XYKYUXYNQDXZTD-UHFFFAOYSA-N tert-butyl n-methyl-n-pyrrolidin-3-ylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)C1CCNC1 XYKYUXYNQDXZTD-UHFFFAOYSA-N 0.000 description 1
UJJLJRQIPMGXEZ-UHFFFAOYSA-N tetrahydro-2-furoic acid Chemical compound OC(=O)C1CCCO1 UJJLJRQIPMGXEZ-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
150000003568 thioethers Chemical group 0.000 description 1
150000003573 thiols Chemical group 0.000 description 1
150000003577 thiophenes Chemical class 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
230000004584 weight gain Effects 0.000 description 1
235000019786 weight gain Nutrition 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
ORXQGKIUCDPEAJ-YRNVUSSQSA-N xanthohumol Chemical compound COC1=CC(O)=C(CC=C(C)C)C(O)=C1C(=O)\C=C\C1=CC=C(O)C=C1 ORXQGKIUCDPEAJ-YRNVUSSQSA-N 0.000 description 1
UVBDKJHYMQEAQV-UHFFFAOYSA-N xanthohumol Natural products OC1=C(CC=C(C)C)C(OC)=CC(OC)=C1C(=O)C=CC1=CC=C(O)C=C1 UVBDKJHYMQEAQV-UHFFFAOYSA-N 0.000 description 1
235000008209 xanthohumol Nutrition 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CA2686951A 2007-05-22 2008-05-13 Inhibiteurs de diacylglycerol acyltransferase Expired - Fee Related CA2686951C (fr)

Applications Claiming Priority (9)

Application Number	Priority Date	Filing Date	Title
US93132707P	2007-05-22	2007-05-22
US93127307P	2007-05-22	2007-05-22
US93136907P	2007-05-22	2007-05-22
US93130307P	2007-05-22	2007-05-22
US60/931,327		2007-05-22
US60/931,303		2007-05-22
US60/931,273		2007-05-22
US60/931,369		2007-05-22
PCT/EP2008/055843 WO2008141976A1 (fr)	2007-05-22	2008-05-13	Inhibiteurs de diacylglycérol acyltransférase

Publications (2)

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CA2686951A1 CA2686951A1 (fr)	2008-11-27
CA2686951C true CA2686951C (fr)	2016-03-22

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CA2686951A Expired - Fee Related CA2686951C (fr)	2007-05-22	2008-05-13	Inhibiteurs de diacylglycerol acyltransferase

Country Status (7)

Country	Link
EP (1)	EP2155687A1 (fr)
CN (1)	CN101835757B (fr)
AU (1)	AU2008253118B2 (fr)
BR (1)	BRPI0811947A2 (fr)
CA (1)	CA2686951C (fr)
MX (1)	MX2009012285A (fr)
WO (1)	WO2008141976A1 (fr)

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AR058562A1 (es)	2005-12-22	2008-02-13	Astrazeneca Ab	Derivados de pirimido [4,5 b] (1,4) oxazinas , procedimientos de obtencion y su uso como inhibidores de acetil coa y dgat 1
WO2007126957A2 (fr)	2006-03-31	2007-11-08	Novartis Ag	Nouveaux composés
BRPI0712802A2 (pt)	2006-05-30	2012-10-23	Astrazeneca Ab	composto, métodos para produzir uma inibição da atividade de dgat1, e para tratar diabete melito e/ou obesidade em um animal de sangue quente, uso de um composto, composição farmacêutica, e, processo para preparar um composto
US8153644B2 (en)	2007-05-22	2012-04-10	Madrigal Pharmaceuticals, Inc.	Diacylglycerol acyltransferase inhibitors
US8115011B2 (en)	2007-05-22	2012-02-14	Madrigal Pharmaceuticals, Inc.	Diacylglycerol acyltransferase inhibitors
US8058299B2 (en)	2007-05-22	2011-11-15	Via Pharmaceuticals, Inc.	Diacylglycerol acyltransferase inhibitors
AU2008258487B2 (en)	2007-06-08	2012-11-15	Janssen Pharmaceutica N.V.	Piperidine/piperazine derivatives
CA2687918C (fr)	2007-06-08	2016-11-08	Janssen Pharmaceutica N.V.	Derives de piperidine/piperazine
EP2152271B1 (fr)	2007-06-08	2015-10-21	Janssen Pharmaceutica, N.V.	Dérivés de piperidine/piperazine
JO2972B1 (en)	2007-06-08	2016-03-15	جانسين فارماسوتيكا ان. في	Piperidine / piperazine derivatives
AR066169A1 (es)	2007-09-28	2009-07-29	Novartis Ag	Derivados de benzo-imidazoles, utiles para trastornos asociados con la actividad de dgat
JP5579170B2 (ja) *	2008-06-05	2014-08-27	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	Ｄｇａｔ阻害剤とｐｐａｒ作動薬を含有する薬剤組み合わせ物
US8211884B2 (en)	2008-08-06	2012-07-03	Madrigal Pharmaceuticals, Inc.	Diacylglycerol acyltransferase inhibitors
US8324385B2 (en)	2008-10-30	2012-12-04	Madrigal Pharmaceuticals, Inc.	Diacylglycerol acyltransferase inhibitors
JP2012509274A (ja)	2008-11-19	2012-04-19	シェーリングコーポレイション	ジアシルグリセロールアシルトランスフェラーゼの阻害薬
EP2367817A4 (fr) *	2008-12-03	2012-05-09	Via Pharmaceuticals Inc	Inhibiteurs de l'enzyme diacylglycérol acyltransférase
US8211914B2 (en)	2008-12-17	2012-07-03	Madrigal Pharmaceuticals, Inc.	Inhibitors of diacylglycerol acyltransferase
US8889674B2 (en)	2009-03-05	2014-11-18	Shionogi & Co., Ltd.	Piperidine and pyrrolidine derivatives having NPY Y5 receptor antagonism
WO2011078102A1 (fr) *	2009-12-22	2011-06-30	第一三共株式会社	Nouveau dérivé de phénoxypyrimidine
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CN103237800B (zh) *	2010-10-14	2015-10-21	田边三菱制药株式会社	酰胺衍生物及其用途
TW201236685A (en) *	2010-11-11	2012-09-16	Daiichi Sankyo Co Ltd	New pyrazole amide derivatives
US9458151B2 (en) *	2011-08-11	2016-10-04	Jikai Biosciences, Inc.	Isothiazole derivatives as PIM kinase inhibitors and preparation methods and use in medicinal manufacture thereof
US9453003B2 (en) *	2011-08-11	2016-09-27	Jikai Biosciences, Inc.	Pyrimidine derivatives as PIM kinase inhibitors and preparation methods and use in medicinal manufacture thereof
CN102924444B (zh) *	2011-08-11	2015-07-08	上海吉铠医药科技有限公司	Pim激酶抑制剂及其制备方法与在制药中的应用
US9452995B2 (en) *	2011-08-11	2016-09-27	Jikai Biosciences, Inc.	Pyridine derivatives as PIM kinase inhibitors and preparation methods and use in medicinal manufacture thereof
WO2013154173A1 (fr)	2012-04-13	2013-10-17	田辺三菱製薬株式会社	Dérivé d'amidopyridine, et son utilisation
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CN104610187B (zh) *	2015-02-10	2016-04-06	佛山市赛维斯医药科技有限公司	一类含脒结构的烷氧苯基噻唑羧酸酰胺类双靶点抑制剂、其制备方法及用途
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AU2008253118B2 (en)	2013-11-21
AU2008253118A1 (en)	2008-11-27
CA2686951A1 (fr)	2008-11-27
CN101835757B (zh)	2014-03-05
WO2008141976A1 (fr)	2008-11-27
BRPI0811947A2 (pt)	2014-11-11
EP2155687A1 (fr)	2010-02-24
MX2009012285A (es)	2009-12-15
CN101835757A (zh)	2010-09-15
HK1148519A1 (en)	2011-09-09

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