MXPA06014574A - Piperidinas n-sustituidas y su uso como farmaceuticos. - Google Patents
Piperidinas n-sustituidas y su uso como farmaceuticos.Info
- Publication number
- MXPA06014574A MXPA06014574A MXPA06014574A MXPA06014574A MXPA06014574A MX PA06014574 A MXPA06014574 A MX PA06014574A MX PA06014574 A MXPA06014574 A MX PA06014574A MX PA06014574 A MXPA06014574 A MX PA06014574A MX PA06014574 A MXPA06014574 A MX PA06014574A
- Authority
- MX
- Mexico
- Prior art keywords
- carboxamide
- cycloalkyl
- heterocycloalkyl
- piperidine
- alkyl
- Prior art date
Links
- -1 N-substituted piperidines Chemical class 0.000 title claims abstract description 244
- 239000003814 drug Substances 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 305
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 50
- 201000010099 disease Diseases 0.000 claims abstract description 36
- 230000000694 effects Effects 0.000 claims abstract description 36
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 claims abstract description 24
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229960002478 aldosterone Drugs 0.000 claims abstract description 24
- 230000014509 gene expression Effects 0.000 claims abstract description 13
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 231
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 218
- 238000000034 method Methods 0.000 claims description 216
- 125000000217 alkyl group Chemical group 0.000 claims description 179
- 125000003118 aryl group Chemical group 0.000 claims description 165
- 125000001072 heteroaryl group Chemical group 0.000 claims description 163
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 129
- 239000000203 mixture Substances 0.000 claims description 111
- 125000001188 haloalkyl group Chemical group 0.000 claims description 108
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 96
- 229910052799 carbon Inorganic materials 0.000 claims description 85
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 84
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims description 72
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 61
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 55
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 51
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 50
- BVOCPVIXARZNQN-UHFFFAOYSA-N nipecotamide Chemical compound NC(=O)C1CCCNC1 BVOCPVIXARZNQN-UHFFFAOYSA-N 0.000 claims description 47
- 238000006243 chemical reaction Methods 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 40
- 125000003342 alkenyl group Chemical group 0.000 claims description 36
- 229960000890 hydrocortisone Drugs 0.000 claims description 36
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 125000004432 carbon atom Chemical group C* 0.000 claims description 34
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 31
- 125000005466 alkylenyl group Chemical group 0.000 claims description 30
- 125000004429 atom Chemical group 0.000 claims description 29
- 125000000304 alkynyl group Chemical group 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 claims description 23
- 206010020772 Hypertension Diseases 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 229960004544 cortisone Drugs 0.000 claims description 22
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 claims description 21
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 claims description 21
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 21
- 206010022489 Insulin Resistance Diseases 0.000 claims description 19
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 19
- 208000008589 Obesity Diseases 0.000 claims description 19
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 19
- 235000020824 obesity Nutrition 0.000 claims description 19
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 19
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 17
- 230000005764 inhibitory process Effects 0.000 claims description 16
- 125000003282 alkyl amino group Chemical group 0.000 claims description 15
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 14
- 239000000651 prodrug Substances 0.000 claims description 14
- 229940002612 prodrug Drugs 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 10
- 229910052702 rhenium Inorganic materials 0.000 claims description 10
- 229910052721 tungsten Inorganic materials 0.000 claims description 10
- 241000009298 Trigla lyra Species 0.000 claims description 9
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 7
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 7
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 6
- 230000006378 damage Effects 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 5
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 5
- 206010012289 Dementia Diseases 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 5
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000004306 triazinyl group Chemical group 0.000 claims description 5
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 4
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 4
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 4
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 4
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 208000001132 Osteoporosis Diseases 0.000 claims description 4
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 208000010877 cognitive disease Diseases 0.000 claims description 4
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 3
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 206010070901 Diabetic dyslipidaemia Diseases 0.000 claims description 3
- 208000005189 Embolism Diseases 0.000 claims description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 3
- 206010061218 Inflammation Diseases 0.000 claims description 3
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
- 208000029078 coronary artery disease Diseases 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 claims description 3
- 230000002792 vascular Effects 0.000 claims description 3
- ZLZOAMCBQXFVAE-ZDUSSCGKSA-N (3s)-1-(3-chloro-2-fluorophenyl)sulfonyl-n-cyclohexylpiperidine-3-carboxamide Chemical compound FC1=C(Cl)C=CC=C1S(=O)(=O)N1C[C@@H](C(=O)NC2CCCCC2)CCC1 ZLZOAMCBQXFVAE-ZDUSSCGKSA-N 0.000 claims description 2
- ZLPRPBUYUNTRAJ-INIZCTEOSA-N (3s)-1-(3-chloro-2-methylphenyl)sulfonyl-n-cycloheptylpiperidine-3-carboxamide Chemical compound CC1=C(Cl)C=CC=C1S(=O)(=O)N1C[C@@H](C(=O)NC2CCCCCC2)CCC1 ZLPRPBUYUNTRAJ-INIZCTEOSA-N 0.000 claims description 2
- ODRPEKCTTLECBX-HNNXBMFYSA-N (3s)-1-(3-chloro-2-methylphenyl)sulfonyl-n-cyclohexylpiperidine-3-carboxamide Chemical compound CC1=C(Cl)C=CC=C1S(=O)(=O)N1C[C@@H](C(=O)NC2CCCCC2)CCC1 ODRPEKCTTLECBX-HNNXBMFYSA-N 0.000 claims description 2
- SFFOXPSWWCTHRH-ZDUSSCGKSA-N (3s)-1-(3-chloro-4-fluorophenyl)sulfonyl-n-cyclohexylpiperidine-3-carboxamide Chemical compound C1=C(Cl)C(F)=CC=C1S(=O)(=O)N1C[C@@H](C(=O)NC2CCCCC2)CCC1 SFFOXPSWWCTHRH-ZDUSSCGKSA-N 0.000 claims description 2
- SROXMWXRTDHRDS-ZDUSSCGKSA-N (3s)-1-(3-chlorophenyl)sulfonyl-n-cyclopentylpiperidine-3-carboxamide Chemical compound ClC1=CC=CC(S(=O)(=O)N2C[C@H](CCC2)C(=O)NC2CCCC2)=C1 SROXMWXRTDHRDS-ZDUSSCGKSA-N 0.000 claims description 2
- XEDBAWHPEVFYKJ-GRTSSRMGSA-N (3s)-1-(5-bromopyridin-2-yl)-n-(4-hydroxycyclohexyl)piperidine-3-carboxamide Chemical compound C1CC(O)CCC1NC(=O)[C@@H]1CN(C=2N=CC(Br)=CC=2)CCC1 XEDBAWHPEVFYKJ-GRTSSRMGSA-N 0.000 claims description 2
- VRLHYJZLHNZLLB-ZDUSSCGKSA-N (3s)-1-(5-chloro-2-fluorophenyl)sulfonyl-n-cyclohexylpiperidine-3-carboxamide Chemical compound FC1=CC=C(Cl)C=C1S(=O)(=O)N1C[C@@H](C(=O)NC2CCCCC2)CCC1 VRLHYJZLHNZLLB-ZDUSSCGKSA-N 0.000 claims description 2
- NBNZATXXBBNSND-GTPINHCMSA-N (3s)-1-benzoyl-n-(4-hydroxycyclohexyl)piperidine-3-carboxamide Chemical compound C1CC(O)CCC1NC(=O)[C@@H]1CN(C(=O)C=2C=CC=CC=2)CCC1 NBNZATXXBBNSND-GTPINHCMSA-N 0.000 claims description 2
- CAERBIPFBFQLQI-OOHWJJMZSA-N (3s)-3-n-(4-hydroxycyclohexyl)-1-n-phenylpiperidine-1,3-dicarboxamide Chemical compound C1CC(O)CCC1NC(=O)[C@@H]1CN(C(=O)NC=2C=CC=CC=2)CCC1 CAERBIPFBFQLQI-OOHWJJMZSA-N 0.000 claims description 2
- RCVUAUUNAWOXMV-ONUXSRJRSA-N (3s)-n-(1-adamantyl)-1-phenylpiperidine-3-carboxamide Chemical compound C([C@@H](C1)C(NC23CC4CC(CC(C4)C2)C3)=O)CCN1C1=CC=CC=C1 RCVUAUUNAWOXMV-ONUXSRJRSA-N 0.000 claims description 2
- LQIWZYZIPDRHIL-INIZCTEOSA-N (3s)-n-(1-methylcyclohexyl)-1-phenylpiperidine-3-carboxamide Chemical compound O=C([C@@H]1CN(CCC1)C=1C=CC=CC=1)NC1(C)CCCCC1 LQIWZYZIPDRHIL-INIZCTEOSA-N 0.000 claims description 2
- RAOIEIGLRGMSIY-COIXEQEXSA-N (3s)-n-(3-hydroxy-1-adamantyl)-1-phenylpiperidine-3-carboxamide Chemical compound C([C@@H](C1)C(=O)NC23CC4CC(C2)CC(C4)(C3)O)CCN1C1=CC=CC=C1 RAOIEIGLRGMSIY-COIXEQEXSA-N 0.000 claims description 2
- CRAVCTWTIULTBS-AOCRQIFASA-N (3s)-n-(4-hydroxycyclohexyl)-1-(2-methylquinolin-4-yl)piperidine-3-carboxamide Chemical compound O=C([C@H]1CCCN(C1)C=1C=C(N=C2C=CC=CC2=1)C)NC1CCC(O)CC1 CRAVCTWTIULTBS-AOCRQIFASA-N 0.000 claims description 2
- WGNFHUKHVIFQDE-MWXLCCTBSA-N (3s)-n-(4-hydroxycyclohexyl)-1-(5-phenylpyridin-2-yl)piperidine-3-carboxamide Chemical compound C1CC(O)CCC1NC(=O)[C@@H]1CN(C=2N=CC(=CC=2)C=2C=CC=CC=2)CCC1 WGNFHUKHVIFQDE-MWXLCCTBSA-N 0.000 claims description 2
- XJGHZOYIEZBFLA-DAFXYXGESA-N (3s)-n-[1-(4-chlorophenyl)propan-2-yl]-1-phenylpiperidine-3-carboxamide Chemical compound O=C([C@@H]1CN(CCC1)C=1C=CC=CC=1)NC(C)CC1=CC=C(Cl)C=C1 XJGHZOYIEZBFLA-DAFXYXGESA-N 0.000 claims description 2
- QZBDPAMWZLSFIX-INIZCTEOSA-N (3s)-n-cyclohexyl-1-(2-methylphenyl)piperidine-3-carboxamide Chemical compound CC1=CC=CC=C1N1C[C@@H](C(=O)NC2CCCCC2)CCC1 QZBDPAMWZLSFIX-INIZCTEOSA-N 0.000 claims description 2
- LZFNWPKAIZQXGJ-HNNXBMFYSA-N (3s)-n-cyclohexyl-1-(3-methoxyphenyl)piperidine-3-carboxamide Chemical compound COC1=CC=CC(N2C[C@H](CCC2)C(=O)NC2CCCCC2)=C1 LZFNWPKAIZQXGJ-HNNXBMFYSA-N 0.000 claims description 2
- SWNUHFZBHNAAPU-INIZCTEOSA-N (3s)-n-cyclohexyl-1-(3-methylphenyl)piperidine-3-carboxamide Chemical compound CC1=CC=CC(N2C[C@H](CCC2)C(=O)NC2CCCCC2)=C1 SWNUHFZBHNAAPU-INIZCTEOSA-N 0.000 claims description 2
- OUHNBYHPDLSUQE-HNNXBMFYSA-N (3s)-n-cyclohexyl-1-(4-fluoro-2-methylphenyl)piperidine-3-carboxamide Chemical compound CC1=CC(F)=CC=C1N1C[C@@H](C(=O)NC2CCCCC2)CCC1 OUHNBYHPDLSUQE-HNNXBMFYSA-N 0.000 claims description 2
- FSXIJYMGOITPDX-IBGZPJMESA-N (3s)-n-cyclohexyl-1-(4-phenoxyphenyl)piperidine-3-carboxamide Chemical compound O=C([C@@H]1CN(CCC1)C=1C=CC(OC=2C=CC=CC=2)=CC=1)NC1CCCCC1 FSXIJYMGOITPDX-IBGZPJMESA-N 0.000 claims description 2
- RKMJNYJFZLPULL-AWEZNQCLSA-N (3s)-n-cyclohexyl-1-[3-(trifluoromethyl)phenyl]piperidine-3-carboxamide Chemical compound FC(F)(F)C1=CC=CC(N2C[C@H](CCC2)C(=O)NC2CCCCC2)=C1 RKMJNYJFZLPULL-AWEZNQCLSA-N 0.000 claims description 2
- JDDUYMMKDTZDBF-ZDUSSCGKSA-N (3s)-n-cyclohexyl-1-[5-(trifluoromethyl)pyridin-2-yl]piperidine-3-carboxamide Chemical compound N1=CC(C(F)(F)F)=CC=C1N1C[C@@H](C(=O)NC2CCCCC2)CCC1 JDDUYMMKDTZDBF-ZDUSSCGKSA-N 0.000 claims description 2
- OPXWDPIAYYNTMY-HNNXBMFYSA-N (3s)-n-cyclohexyl-1-phenylpiperidine-3-carboxamide Chemical compound O=C([C@@H]1CN(CCC1)C=1C=CC=CC=1)NC1CCCCC1 OPXWDPIAYYNTMY-HNNXBMFYSA-N 0.000 claims description 2
- JYQSCBJDTKZOKU-ZDUSSCGKSA-N (3s)-n-cyclohexyl-1-pyrazin-2-ylpiperidine-3-carboxamide Chemical compound O=C([C@@H]1CN(CCC1)C=1N=CC=NC=1)NC1CCCCC1 JYQSCBJDTKZOKU-ZDUSSCGKSA-N 0.000 claims description 2
- UZUWPFYUNGCWEP-AWEZNQCLSA-N (3s)-n-cyclohexyl-1-pyridin-2-ylpiperidine-3-carboxamide Chemical compound O=C([C@@H]1CN(CCC1)C=1N=CC=CC=1)NC1CCCCC1 UZUWPFYUNGCWEP-AWEZNQCLSA-N 0.000 claims description 2
- XOVDTJFMSZZWBV-UHFFFAOYSA-N 1-(3-chlorophenyl)sulfonyl-n-cyclohexylpiperidine-3-carboxamide Chemical compound ClC1=CC=CC(S(=O)(=O)N2CC(CCC2)C(=O)NC2CCCCC2)=C1 XOVDTJFMSZZWBV-UHFFFAOYSA-N 0.000 claims description 2
- ILIPCBLDKZNOEK-UHFFFAOYSA-N 1-(benzenesulfonyl)-n-cyclohexyl-n-cyclopropylpiperidine-3-carboxamide Chemical compound C1CC1N(C1CCCCC1)C(=O)C(C1)CCCN1S(=O)(=O)C1=CC=CC=C1 ILIPCBLDKZNOEK-UHFFFAOYSA-N 0.000 claims description 2
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 2
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 claims description 2
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 2
- 125000004494 ethyl ester group Chemical group 0.000 claims description 2
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 2
- BCQZCKHIKRWSGH-HOTGVXAUSA-N methyl (3s)-3-[[(3s)-1-(3-chloro-2-methylphenyl)sulfonylpiperidin-3-yl]carbamoyl]piperidine-1-carboxylate Chemical compound C1N(C(=O)OC)CCC[C@@H]1C(=O)N[C@@H]1CN(S(=O)(=O)C=2C(=C(Cl)C=CC=2)C)CCC1 BCQZCKHIKRWSGH-HOTGVXAUSA-N 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 51
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 4
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- AMBKZGFFDSCPJG-AWEZNQCLSA-N (3s)-1-(1,3-benzoxazol-2-yl)-n-cyclohexylpiperidine-3-carboxamide Chemical compound O=C([C@@H]1CN(CCC1)C=1OC2=CC=CC=C2N=1)NC1CCCCC1 AMBKZGFFDSCPJG-AWEZNQCLSA-N 0.000 claims 1
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- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- 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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
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- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US58255704P | 2004-06-24 | 2004-06-24 | |
| US61457004P | 2004-09-30 | 2004-09-30 | |
| US68684005P | 2005-06-02 | 2005-06-02 | |
| PCT/US2005/022307 WO2006012226A2 (en) | 2004-06-24 | 2005-06-23 | N-substituted piperidines and their use as pharmaceuticals |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA06014574A true MXPA06014574A (es) | 2007-03-12 |
Family
ID=35786661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA06014574A MXPA06014574A (es) | 2004-06-24 | 2005-06-23 | Piperidinas n-sustituidas y su uso como farmaceuticos. |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US8071624B2 (OSRAM) |
| EP (1) | EP1758580A4 (OSRAM) |
| JP (1) | JP2008504275A (OSRAM) |
| AU (1) | AU2005267289A1 (OSRAM) |
| BR (1) | BRPI0512535A (OSRAM) |
| CA (1) | CA2570637A1 (OSRAM) |
| CR (1) | CR8793A (OSRAM) |
| EA (1) | EA200700117A1 (OSRAM) |
| EC (1) | ECSP067114A (OSRAM) |
| IL (1) | IL179520A0 (OSRAM) |
| MX (1) | MXPA06014574A (OSRAM) |
| NZ (1) | NZ551603A (OSRAM) |
| WO (1) | WO2006012226A2 (OSRAM) |
Families Citing this family (102)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100222316A1 (en) * | 2004-04-29 | 2010-09-02 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme |
| US7880001B2 (en) * | 2004-04-29 | 2011-02-01 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme |
| US8415354B2 (en) | 2004-04-29 | 2013-04-09 | Abbott Laboratories | Methods of use of inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme |
| TWI350168B (en) | 2004-05-07 | 2011-10-11 | Incyte Corp | Amido compounds and their use as pharmaceuticals |
| AU2005267331A1 (en) * | 2004-06-24 | 2006-02-02 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| BRPI0512410A (pt) * | 2004-06-24 | 2008-03-04 | Incyte Corp | compostos de amido e seu uso como produtos farmacêuticos |
| CA2589565A1 (en) * | 2004-06-24 | 2006-01-05 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| EP1768954A4 (en) * | 2004-06-24 | 2008-05-28 | Incyte Corp | 2-METHYLPROPANAMIDES AND THEIR USE AS PHARMACEUTICALS |
| EP1773780A4 (en) * | 2004-06-24 | 2008-01-09 | Incyte Corp | AMIDO COMPOUNDS AND USES THEREOF AS PHARMACEUTICAL PRODUCTS |
| BRPI0512535A (pt) | 2004-06-24 | 2008-03-25 | Incyte Corp | compostos de piperidinas n-substituìdas, suas composições e métodos de modulações |
| AU2005273986A1 (en) * | 2004-08-10 | 2006-02-23 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| US8110581B2 (en) | 2004-11-10 | 2012-02-07 | Incyte Corporation | Lactam compounds and their use as pharmaceuticals |
| AU2005304560C1 (en) * | 2004-11-10 | 2013-05-09 | Incyte Holdings Corporation | Lactam compounds and their use as pharmaceuticals |
| CN101103016A (zh) * | 2004-11-18 | 2008-01-09 | 因塞特公司 | 11-β羟基类固醇脱氢酶1型抑制剂及其使用方法 |
| ATE555081T1 (de) * | 2005-01-05 | 2012-05-15 | Abbott Lab | Adamantyl-derivate als inhibitoren des 11-beta- hydroxysteroid-dehydrogenase-1-enzyms |
| US20090192198A1 (en) | 2005-01-05 | 2009-07-30 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme |
| US8198331B2 (en) | 2005-01-05 | 2012-06-12 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme |
| CN102816081A (zh) * | 2005-01-05 | 2012-12-12 | 雅培制药有限公司 | 11-β-羟甾类脱氢酶1型酶的抑制剂 |
| RU2007129779A (ru) * | 2005-01-06 | 2009-02-20 | Астразенека Аб (Se) | Новые соединения пиридина |
| KR100979577B1 (ko) * | 2005-03-03 | 2010-09-01 | 에프. 호프만-라 로슈 아게 | 2형 진성 당뇨병의 치료를 위한11-베타-하이드록시스테로이드 탈수소효소의 억제제로서1-설폰일-피페리딘-3-카복실산 아마이드 유도체 |
| JP5140577B2 (ja) * | 2005-03-31 | 2013-02-06 | タケダ カリフォルニア インコーポレイテッド | ヒドロキシステロイドデヒドロゲナーゼ阻害剤 |
| WO2006113261A2 (en) * | 2005-04-14 | 2006-10-26 | Bristol-Myers Squibb Company | Inhibitors of 11-beta hydroxysteroid dehydrogenase type i |
| US7820699B2 (en) | 2005-04-27 | 2010-10-26 | Hoffmann-La Roche Inc. | Cyclic amines |
| WO2007046867A2 (en) * | 2005-05-19 | 2007-04-26 | Xenon Pharmaceuticals Inc. | Piperidine derivatives and their uses as therapeutic agents |
| MX2008000470A (es) * | 2005-07-13 | 2008-03-11 | Astrazeneca Ab | Analogos de piridina nuevos. |
| CA2621255A1 (en) * | 2005-09-21 | 2007-04-05 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| AU2006322060A1 (en) * | 2005-12-05 | 2007-06-14 | Incyte Corporation | Lactam compounds and methods of using the same |
| WO2007084314A2 (en) * | 2006-01-12 | 2007-07-26 | Incyte Corporation | MODULATORS OF 11-ß HYDROXYL STEROID DEHYDROGENASE TYPE 1, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USING THE SAME |
| BRPI0707408A2 (pt) * | 2006-01-31 | 2011-05-03 | Incyte Corp | compostos de amido e seu uso como produtos farmacêuticos |
| JP5099814B2 (ja) * | 2006-02-02 | 2012-12-19 | 田辺三菱製薬株式会社 | 含窒素複素二環式化合物 |
| RU2008132333A (ru) | 2006-02-07 | 2010-03-20 | Вайет (Us) | Ингибиторы 11-бета hsd1 |
| WO2007101270A1 (en) * | 2006-03-02 | 2007-09-07 | Incyte Corporation | MODULATORS OF 11-β HYDROXYL STEROID DEHYDROGENASE TYPE 1, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USING THE SAME |
| US20070208001A1 (en) * | 2006-03-03 | 2007-09-06 | Jincong Zhuo | Modulators of 11- beta hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same |
| US20070293529A1 (en) * | 2006-05-01 | 2007-12-20 | Yun-Long Li | Tetrasubstituted ureas as modulators of 11-beta hydroxyl steroid dehydrogenase type 1 |
| PE20080251A1 (es) | 2006-05-04 | 2008-04-25 | Boehringer Ingelheim Int | Usos de inhibidores de dpp iv |
| US7838544B2 (en) | 2006-05-17 | 2010-11-23 | Incyte Corporation | Heterocyclic inhibitors of 11-β hydroxyl steroid dehydrogenase type 1 and methods of using the same |
| TW200808695A (en) * | 2006-06-08 | 2008-02-16 | Amgen Inc | Benzamide derivatives and uses related thereto |
| TW200815426A (en) * | 2006-06-28 | 2008-04-01 | Astrazeneca Ab | New pyridine analogues II 333 |
| TW200811133A (en) * | 2006-07-04 | 2008-03-01 | Astrazeneca Ab | New pyridine analogues III 334 |
| WO2008004943A1 (en) * | 2006-07-04 | 2008-01-10 | Astrazeneca Ab | New pyridine analogues |
| JP2009542641A (ja) * | 2006-07-04 | 2009-12-03 | アストラゼネカ アクチボラグ | 新規ピリジン類縁体 |
| EP2041115A4 (en) * | 2006-07-04 | 2010-07-07 | Astrazeneca Ab | NEW PYRIDINE ANALOG |
| EP1918285A1 (en) * | 2006-11-03 | 2008-05-07 | Merck Sante | Diazepane-acetamide derivatives as selective 11beta-HSD1 inhibitors |
| US20080200448A1 (en) * | 2007-01-12 | 2008-08-21 | Astrazeneca Ab | New Pyridine Analogues VIII 518 |
| RU2009123928A (ru) * | 2007-01-12 | 2011-02-20 | Астразенека Аб (Se) | Пиридиновые соединения и их применение в качестве антагонистов p2y12 |
| US20080176827A1 (en) * | 2007-01-12 | 2008-07-24 | Astrazeneca Ab | New Pyridine Analogues VII 543 |
| WO2008145681A2 (en) * | 2007-05-31 | 2008-12-04 | Boehringer Ingelheim International Gmbh | Ccr2 receptor antagonists and uses thereof |
| CL2008001839A1 (es) | 2007-06-21 | 2009-01-16 | Incyte Holdings Corp | Compuestos derivados de 2,7-diazaespirociclos, inhibidores de 11-beta hidroxil esteroide deshidrogenasa tipo 1; composicion farmaceutica que comprende a dichos compuestos; utiles para tratar la obesidad, diabetes, intolerancia a la glucosa, diabetes tipo ii, entre otras enfermedades. |
| US20090018166A1 (en) * | 2007-07-13 | 2009-01-15 | Astrazeneca Ab | New Pyridine Analogues X 161 |
| JP5736098B2 (ja) * | 2007-08-21 | 2015-06-17 | アッヴィ・インコーポレイテッド | 中枢神経系障害を治療するための医薬組成物 |
| DE102008010221A1 (de) | 2008-02-20 | 2009-08-27 | Bayer Healthcare Ag | Heteroaryl-substituierte Piperidine |
| DE102007057718A1 (de) | 2007-11-30 | 2009-07-30 | Bayer Healthcare Ag | Heteroaryl-substituierte Piperidine |
| DK2227466T3 (da) * | 2007-11-30 | 2011-08-08 | Bayer Schering Pharma Ag | Heteroaryl-substituerede piperidiner |
| TW200944526A (en) | 2008-04-22 | 2009-11-01 | Vitae Pharmaceuticals Inc | Carbamate and urea inhibitors of 11β-hydroxysteroid dehydrogenase 1 |
| JP5502077B2 (ja) | 2008-06-05 | 2014-05-28 | グラクソ グループ リミテッド | 新規な化合物 |
| ES2445199T3 (es) | 2008-06-05 | 2014-02-28 | Glaxo Group Limited | Derivados de benzpirazol como inhibidores de PI3-quinasas |
| EP2280705B1 (en) | 2008-06-05 | 2014-10-08 | Glaxo Group Limited | Novel compounds |
| US8273900B2 (en) | 2008-08-07 | 2012-09-25 | Novartis Ag | Organic compounds |
| LT2349324T (lt) * | 2008-10-17 | 2017-12-27 | Sanofi-Aventis Deutschland Gmbh | Insulino ir glp-1 agonisto derinys |
| CN102256963B (zh) | 2008-12-19 | 2014-06-11 | 贝林格尔.英格海姆国际有限公司 | 作为ccr2受体拮抗剂用于治疗炎症、哮喘和copd的环状嘧啶-4-甲酰胺 |
| LT3508477T (lt) * | 2008-12-22 | 2022-02-10 | Chemocentryx, Inc. | C5ar antagonistai |
| US8524751B2 (en) | 2009-03-09 | 2013-09-03 | GlaxoSmithKline Intellecutual Property Development | 4-oxadiazol-2-YL-indazoles as inhibitors of P13 kinases |
| DE102009014484A1 (de) | 2009-03-23 | 2010-09-30 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Piperidine |
| ES2644724T3 (es) | 2009-04-30 | 2017-11-30 | Glaxo Group Limited | Indazoles sustituidos con oxazol como inhibidores de PI3-cinasas |
| DE102009022896A1 (de) | 2009-05-27 | 2010-12-02 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Piperidine |
| DE102009022894A1 (de) * | 2009-05-27 | 2010-12-02 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Piperidine |
| DE102009022895A1 (de) * | 2009-05-27 | 2010-12-02 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Piperidine |
| DE102009022897A1 (de) | 2009-05-27 | 2010-12-02 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Piperidine |
| ES2350077B1 (es) | 2009-06-04 | 2011-11-04 | Laboratorios Salvat, S.A. | Compuestos inhibidores de 11beta-hidroxiesteroide deshidrogenasa de tipo 1. |
| CN102711804B (zh) | 2009-11-13 | 2015-09-16 | 赛诺菲-安万特德国有限公司 | 包含glp-1激动剂和甲硫氨酸的药物组合物 |
| JP5832439B2 (ja) | 2009-11-13 | 2015-12-16 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Ｇｌｐ−１アゴニスト、インスリン及びメチオニンを含む薬学的組成物 |
| PT2513093E (pt) | 2009-12-17 | 2014-10-22 | Boehringer Ingelheim Int | Novos antagonistas do receptor ccr2 e suas utilizações |
| EP2569298B1 (en) | 2010-05-12 | 2015-11-25 | Boehringer Ingelheim International GmbH | Novel ccr2 receptor antagonists, method for producing the same, and use thereof as medicaments |
| US8946218B2 (en) | 2010-05-12 | 2015-02-03 | Boehringer Ingelheim International Gmbh | CCR2 receptor antagonists, method for producing the same, and use thereof as medicaments |
| JP5647339B2 (ja) | 2010-05-17 | 2014-12-24 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｃｒ２アンタゴニスト及びこれらの使用 |
| JP5636094B2 (ja) | 2010-05-25 | 2014-12-03 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｃｒ２受容体アンタゴニスト |
| US8962656B2 (en) | 2010-06-01 | 2015-02-24 | Boehringer Ingelheim International Gmbh | CCR2 antagonists |
| SI2585064T1 (sl) * | 2010-06-24 | 2017-08-31 | Chemocentryx, Inc. | Antagonisti C5AR |
| CN103179978A (zh) | 2010-08-30 | 2013-06-26 | 赛诺菲-安万特德国有限公司 | Ave0010用于制造供治疗2型糖尿病用的药物的用途 |
| CN103298786B (zh) * | 2010-10-11 | 2016-01-20 | 埃克希金医药品有限公司 | 芳基磺酰胺盐ccr3拮抗剂 |
| GB201018124D0 (en) | 2010-10-27 | 2010-12-08 | Glaxo Group Ltd | Polymorphs and salts |
| US9821032B2 (en) | 2011-05-13 | 2017-11-21 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin |
| JP5786258B2 (ja) | 2011-07-15 | 2015-09-30 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規かつ選択的なｃｃｒ２拮抗薬 |
| WO2013030160A1 (en) | 2011-08-29 | 2013-03-07 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for use in glycemic control in diabetes type 2 patients |
| TWI559929B (en) | 2011-09-01 | 2016-12-01 | Sanofi Aventis Deutschland | Pharmaceutical composition for use in the treatment of a neurodegenerative disease |
| JP2016505000A (ja) | 2012-12-21 | 2016-02-18 | エピザイム，インコーポレイティド | Ｐｒｍｔ５阻害剤およびその使用 |
| WO2014100716A1 (en) | 2012-12-21 | 2014-06-26 | Epizyme, Inc. | Prmt5 inhibitors and uses thereof |
| US9604930B2 (en) | 2012-12-21 | 2017-03-28 | Epizyme, Inc. | Tetrahydro- and dihydro-isoquinoline PRMT5 inhibitors and uses thereof |
| JP2016505002A (ja) | 2012-12-21 | 2016-02-18 | エピザイム，インコーポレイティド | ジヒドロイソキノリンまたはテトラヒドロイソキノリンを含有するｐｒｍｔ５阻害剤およびその使用 |
| JP2016505597A (ja) | 2012-12-21 | 2016-02-25 | エピザイム，インコーポレイティド | Ｐｒｍｔ５阻害剤およびその使用 |
| US9399194B2 (en) * | 2014-07-16 | 2016-07-26 | Battelle Energy Alliance, Llc | Methods for treating a liquid using draw solutions |
| WO2016022605A1 (en) | 2014-08-04 | 2016-02-11 | Epizyme, Inc. | Prmt5 inhibitors and uses thereof |
| ES2926828T3 (es) | 2014-09-29 | 2022-10-28 | Chemocentryx Inc | Procesos e intermedios en la preparación de antagonistas de C5aR |
| MA41138B1 (fr) | 2014-12-12 | 2023-07-31 | Sanofi Aventis Deutschland | Formulation à rapport fixe d'insuline glargine/lixisenatide |
| TWI748945B (zh) | 2015-03-13 | 2021-12-11 | 德商賽諾菲阿凡提斯德意志有限公司 | 第２型糖尿病病患治療 |
| TW201705975A (zh) | 2015-03-18 | 2017-02-16 | 賽諾菲阿凡提斯德意志有限公司 | 第２型糖尿病病患之治療 |
| AU2016287584B2 (en) | 2015-07-02 | 2020-03-26 | Centrexion Therapeutics Corporation | (4-((3R,4R)-3-methoxytetrahydro-pyran-4-ylamino)piperidin-1-yl)(5-methyl-6-(((2R,6S)-6-(p-tolyl)tetrahydro-2H-pyran-2-yl)methylamino)pyrimidin-4yl)methanone citrate |
| JP7339733B2 (ja) | 2016-01-14 | 2023-09-06 | ケモセントリックス，インコーポレイティド | Ｃ３腎症を処置する方法 |
| EP3235813A1 (en) | 2016-04-19 | 2017-10-25 | Cidqo 2012, S.L. | Aza-tetra-cyclo derivatives |
| CN114539273A (zh) | 2016-06-07 | 2022-05-27 | 北京加科思新药研发有限公司 | 可用作shp2抑制剂的新型杂环衍生物 |
| HRP20241239T1 (hr) | 2017-03-23 | 2024-12-06 | Jacobio Pharmaceuticals Co., Ltd. | Novi heterociklički derivati korisni kao shp2 inhibitori |
| WO2020063760A1 (en) | 2018-09-26 | 2020-04-02 | Jacobio Pharmaceuticals Co., Ltd. | Novel heterocyclic derivatives useful as shp2 inhibitors |
Family Cites Families (115)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL262366A (OSRAM) | 1960-03-14 | |||
| US3201466A (en) | 1963-03-08 | 1965-08-17 | Gulf Oil Corp | Substituted cyclopropanecarboxanilide herbicides |
| US3849403A (en) | 1968-04-29 | 1974-11-19 | American Home Prod | 2,3,4,5-tetrahydro-1,1,5,5-tetrasubstituted-1h-3-benzazepines |
| FR1600908A (en) | 1968-11-14 | 1970-08-03 | Hypocholesterolaemic and anorexigenic - phenoxy alkanoylaralkylamines | |
| DE2114420A1 (de) | 1971-03-25 | 1972-10-05 | Merck Patent Gmbh, 6100 Darmstadt | Substituierte Phenylalkanol-Derivate und Verfahren zu ihrer Herstellung |
| US3923350A (en) | 1974-03-11 | 1975-12-02 | Commercial Metals Company | Precision bearing assembly |
| ES427013A1 (es) | 1974-06-05 | 1976-07-16 | Alter Sa | Un procedimiento de preparacion de ciertas amidas del aci- do 2 - (p - clorofenoxi) - 2 - metilpropionico. |
| GB1460389A (en) | 1974-07-25 | 1977-01-06 | Pfizer Ltd | 4-substituted quinazoline cardiac stimulants |
| US3933829A (en) | 1974-08-22 | 1976-01-20 | John Wyeth & Brother Limited | 4-Aminoquinoline derivatives |
| TR18917A (tr) | 1974-10-31 | 1977-12-09 | Ciba Geigy Ag | 1-(bis-triflormetilfenil)-2-oksopirolidin-4-karbonik asitleri ve bunlarin tuerevleri |
| US3933350A (en) * | 1974-12-09 | 1976-01-20 | Mignano Frank J | Paper insert feeder |
| FR2312247A1 (fr) | 1975-05-30 | 1976-12-24 | Parcor | Derives de la thieno-pyridine, leur procede de preparation et leurs applications |
| US4145435A (en) | 1976-11-12 | 1979-03-20 | The Upjohn Company | 2-aminocycloaliphatic amide compounds |
| JPS57156450A (en) | 1981-03-24 | 1982-09-27 | Ihara Chem Ind Co Ltd | 1-(4-chlorophenyl)-1-cyclopentanecarboxylic acid derivative, its preparation, and aquatic life repellent containing said compound as active component |
| US4439606A (en) | 1982-05-06 | 1984-03-27 | American Cyanamid Company | Antiatherosclerotic 1-piperazinecarbonyl compounds |
| CA1325217C (en) | 1983-11-07 | 1993-12-14 | John T. Lai | 3,5-dialkyl-4-hydroxyphenyl-substituted derivatives |
| JPS60149562A (ja) | 1984-01-13 | 1985-08-07 | Kyorin Pharmaceut Co Ltd | 新規なピペリジン誘導体およびその製法 |
| US4701459A (en) * | 1986-07-08 | 1987-10-20 | Bristol-Myers Company | 7-amino-1,3-dihydro-2H-imidazo[4,5-b]quinolin 2-ones and method for inhibiting phosphodiesterase and blood platelet aggregation |
| FI874212A7 (fi) * | 1986-09-29 | 1988-03-30 | Bristol Myers Squibb Co | 5-arylideeni- ja 5-alkylideenisubstituoitujen hydantoiinien valmistusmenetelmä |
| EP0273659A1 (en) | 1986-12-27 | 1988-07-06 | Takeda Chemical Industries, Ltd. | Azaspiro compounds, their production and use |
| DE3911670A1 (de) | 1989-04-10 | 1990-10-11 | Schaeffler Waelzlager Kg | Radial-waelzlager |
| DE3920616A1 (de) | 1989-06-23 | 1991-01-03 | Boehringer Mannheim Gmbh | Arzneimittel, enthaltend di-tert.-butylhydroxyphenyl-derivate sowie neue derivate |
| US5206240A (en) | 1989-12-08 | 1993-04-27 | Merck & Co., Inc. | Nitrogen-containing spirocycles |
| US5852029A (en) | 1990-04-10 | 1998-12-22 | Israel Institute For Biological Research | Aza spiro compounds acting on the cholinergic system with muscarinic agonist activity |
| FR2672213B1 (fr) | 1991-02-05 | 1995-03-10 | Sanofi Sa | Utilisation de derives 4-(3-trifluoromethylphenyl)-1,2,3,6-tetrahydropyridiniques comme capteurs de radicaux libres. |
| JPH04275271A (ja) | 1991-03-04 | 1992-09-30 | Lederle Japan Ltd | インドメタシン誘導体 |
| JPH04334357A (ja) * | 1991-05-02 | 1992-11-20 | Fujirebio Inc | 酵素阻害作用を有するアシル誘導体 |
| FR2678272B1 (fr) | 1991-06-27 | 1994-01-14 | Synthelabo | Derives de 2-aminopyrimidine-4-carboxamide, leur preparation et leur application en therapeutique. |
| DE4234295A1 (de) * | 1992-10-12 | 1994-04-14 | Thomae Gmbh Dr K | Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| FR2705343B1 (fr) | 1993-05-17 | 1995-07-21 | Fournier Ind & Sante | Dérivés de beta,beta-diméthyl-4-pipéridineéthanamine, leur procédé de préparation et leur utilisation en thérapeutique. |
| DE9403308U1 (de) | 1994-02-28 | 1994-04-28 | INA Wälzlager Schaeffler KG, 91074 Herzogenaurach | Ausgleichsgetriebe für ein Kraftfahrzeug |
| FR2724656B1 (fr) | 1994-09-15 | 1996-12-13 | Adir | Nouveaux derives du benzopyranne, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| PL182502B1 (pl) | 1994-09-27 | 2002-01-31 | Janssen Pharmaceutica Nv | Nowe związki, pochodne bicyklicznego benzoesanu N-podstawionego piperydynylu, środek farmaceutyczny i sposób wytwarzania pochodnych bicyklicznego benzoesanu N-podstawionego piperydynylu |
| FR2734265B1 (fr) | 1995-05-17 | 1997-06-13 | Adir | Nouveaux composes spiro heterocycliques, leur procede de preparation et les compositions pharmaceutiques les contenant |
| US5693567A (en) | 1995-06-07 | 1997-12-02 | Xerox Corporation | Separately etching insulating layer for contacts within array and for peripheral pads |
| FR2736053B1 (fr) | 1995-06-28 | 1997-09-19 | Sanofi Sa | Nouvelles 1-phenylalkyl-1,2,3,6-tetrahydropyridines |
| GB9517622D0 (en) | 1995-08-29 | 1995-11-01 | Univ Edinburgh | Regulation of intracellular glucocorticoid concentrations |
| CA2233204A1 (en) | 1995-09-29 | 1997-04-03 | Joseph A. Jakubowski | Spiro compounds as inhibitors of fibrinogen-dependent platelet aggregation |
| GB9604311D0 (en) * | 1996-02-29 | 1996-05-01 | Merck & Co Inc | Inhibitors of farnesyl-protein transferase |
| GB9600235D0 (en) | 1996-01-05 | 1996-03-06 | Pfizer Ltd | Therapeutic agents |
| RU2194038C2 (ru) | 1996-05-01 | 2002-12-10 | Орто-Макнейл Фармасьютикал, Инк. | Карбоксамидные производные пирролидина или пиперидина, фармацевтическая композиция на их основе и способ ингибирования агрегации тромбоцитов |
| NZ334389A (en) | 1996-08-28 | 2001-05-25 | Ube Industries | Cyclic amine derivatives |
| HUP0000191A2 (hu) * | 1996-09-13 | 2001-04-28 | Schering Corp. | Farnezil-protein-transzferáz inhibitorként alkalmazható új triciklusos piperidinil-vegyületek |
| IL122072A (en) | 1996-11-14 | 2001-03-19 | Akzo Nobel Nv | Piperidine derivatives their preparation and pharmaceutical compositions containing them |
| GB2327609A (en) * | 1997-07-23 | 1999-02-03 | Merck & Co Inc | A method for eliciting an avß5 or dual avß3/avß5 antagonizing effect |
| CA2322171C (en) | 1998-02-27 | 2009-10-27 | Sankyo Company Limited | Cyclic amino compounds |
| US6087368A (en) | 1998-06-08 | 2000-07-11 | Bristol-Myers Squibb Company | Quinazolinone inhibitors of cGMP phosphodiesterase |
| JP2002519428A (ja) | 1998-07-02 | 2002-07-02 | メルク エンド カムパニー インコーポレーテッド | プレニル−タンパク質トランスフェラーゼの阻害剤 |
| DE69918404T2 (de) | 1998-10-16 | 2005-08-04 | Daiichi Suntory Pharma Co., Ltd. | Aminophenoxyessigsäure derivate als neuroschützende mittel |
| KR20010108394A (ko) | 1999-03-26 | 2001-12-07 | 다비드 에 질레스 | 신규 화합물 |
| EP1165500A1 (en) | 1999-04-02 | 2002-01-02 | Du Pont Pharmaceuticals Company | Amide derivatives as inhibitors of matrix metalloproteinases,tnf-alpha,and aggrecanase |
| ES2165274B1 (es) | 1999-06-04 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de indolilpiperidina como agentes antihistaminicos y antialergicos. |
| CA2378202A1 (en) | 1999-07-21 | 2001-01-25 | Odd-Geir Berge | New compounds |
| JP4275271B2 (ja) | 1999-11-15 | 2009-06-10 | 寺崎電気産業株式会社 | 計測表示装置 |
| AU780419C (en) | 1999-12-03 | 2005-09-29 | Ono Pharmaceutical Co. Ltd. | Triazaspiro(5.5)undecane derivatives and drugs containing the same as the active ingredient |
| RU2265021C2 (ru) | 1999-12-03 | 2005-11-27 | Оно Фармасьютикал Ко., Лтд. | Производные триазаспиро[5,5]ундекана (варианты), фармацевтическая композиция и способ регулирования хемокина/рецептора хемокина |
| ATE337292T1 (de) | 2000-04-26 | 2006-09-15 | Warner Lambert Co | Trans-n- 4-(4-hydroxyphenyl)cyclohexylö-3- phenylpropionamid als subtyp-selektiver nmda rezeptor antagonist |
| US7294637B2 (en) | 2000-09-11 | 2007-11-13 | Sepracor, Inc. | Method of treating addiction or dependence using a ligand for a monamine receptor or transporter |
| AUPR079700A0 (en) * | 2000-10-17 | 2000-11-09 | Alchemia Pty Ltd | Combinatorial libraries of monosaccharides |
| US7102009B2 (en) | 2001-01-12 | 2006-09-05 | Amgen Inc. | Substituted amine derivatives and methods of use |
| US7365205B2 (en) | 2001-06-20 | 2008-04-29 | Daiichi Sankyo Company, Limited | Diamine derivatives |
| US6547958B1 (en) | 2001-07-13 | 2003-04-15 | Chevron U.S.A. Inc. | Hydrocarbon conversion using zeolite SSZ-59 |
| US7074788B2 (en) | 2001-11-22 | 2006-07-11 | Biovitrum Ab | Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1 |
| US6818772B2 (en) * | 2002-02-22 | 2004-11-16 | Abbott Laboratories | Antagonists of melanin concentrating hormone effects on the melanin concentrating hormone receptor |
| HRP20040716A2 (en) * | 2002-02-27 | 2005-02-28 | Pfizer Products Inc. | Acc inhibitors |
| GB0213715D0 (en) | 2002-06-14 | 2002-07-24 | Syngenta Ltd | Chemical compounds |
| AU2003241579B9 (en) | 2002-06-19 | 2009-07-30 | Eli Lilly And Company | Amide linker peroxisome proliferator activated receptor modulators |
| SE0202133D0 (sv) | 2002-07-08 | 2002-07-08 | Astrazeneca Ab | Novel compounds |
| AU2003267551A1 (en) | 2002-08-21 | 2004-03-11 | Astrazeneca Ab | Thieno-pyrrole compounds as antagonists of gonadotropin releasing hormone |
| WO2004022554A1 (en) | 2002-09-07 | 2004-03-18 | Celltech R & D Limited | Quinazolinone derivatives |
| EP1551818B1 (en) | 2002-10-09 | 2009-02-04 | Schering Corporation | Thiadiazoledioxides and thiadiazoleoxides as cxc- and cc-chemokine receptor ligands |
| US20040072802A1 (en) | 2002-10-09 | 2004-04-15 | Jingwu Duan | Beta-amino acid derivatives as inhibitors of matrix metalloproteases and TNF-alpha |
| CA2501611A1 (en) | 2002-10-11 | 2004-04-22 | Astrazeneca Ab | 1,4-disubstituted piperidine derivatives and their use as 11-betahsd1 inhibitors |
| WO2004035581A1 (ja) | 2002-10-18 | 2004-04-29 | Ono Pharmaceutical Co., Ltd. | スピロ複素環誘導体化合物およびその化合物を有効成分とする薬剤 |
| WO2004058727A1 (en) | 2002-12-20 | 2004-07-15 | Bayer Pharmaceuticals Corporation | Substituted 3,5-dihydro-4h-imidazol-4-ones for the treatment of obesity |
| RU2333203C2 (ru) | 2002-12-25 | 2008-09-10 | Дайити Фармасьютикал Ко., Лтд. | Диаминовые производные |
| TW200503994A (en) | 2003-01-24 | 2005-02-01 | Novartis Ag | Organic compounds |
| CA2512886A1 (en) | 2003-02-28 | 2004-09-10 | Galderma Research & Development, S.N.C. | Ligands that modulate lxr-type receptors |
| US7205318B2 (en) | 2003-03-18 | 2007-04-17 | Bristol-Myers Squibb Company | Lactam-containing cyclic diamines and derivatives as a factor Xa inhibitors |
| US20040188324A1 (en) | 2003-03-26 | 2004-09-30 | Saleh Elomari | Hydrocarbon conversion using molecular sieve SSZ-65 |
| EP1618090A1 (en) | 2003-04-11 | 2006-01-25 | Novo Nordisk A/S | 11ß-HYDROXYSTEROID DEHYDROGENASE TYPE 1 ACTIVE COMPOUNDS |
| CA2524269A1 (en) | 2003-05-02 | 2004-11-18 | Elan Pharmaceuticals, Inc. | 4- bromo - 5 - (2- chloro - benzoylamino) - 1h - pyrazole - 3 - carboxylic acid amide derivatives and related compounds as bradykinin b1 receptor antagonists for the treatment of inflammatory diseases |
| US7652061B2 (en) | 2003-05-20 | 2010-01-26 | Novartis A.G. | N-acyl nitrogen heterocycles as ligands of peroxisome proliferator-activated receptors |
| SE0302755D0 (sv) | 2003-10-17 | 2003-10-17 | Astrazeneca Ab | Novel compounds |
| GB0325956D0 (en) | 2003-11-06 | 2003-12-10 | Addex Pharmaceuticals Sa | Novel compounds |
| EP1683797A1 (en) | 2003-11-13 | 2006-07-26 | Ono Pharmaceutical Co., Ltd. | Heterocyclic spiro compound |
| AU2004305321A1 (en) | 2003-12-19 | 2005-07-07 | Pfizer Inc. | Benzenesulfonylamino-pyridin-2-yl derivatives and related compounds as inhibitors of 11-beta-hydroxysteroid dehydrogenase type 1 (11-beta-hsd-1) for the treatment of diabetes and obesity |
| WO2005068460A1 (en) | 2003-12-22 | 2005-07-28 | Schering Corporation | Isothiazole dioxides as cxc- and cc- chemokine receptor ligands |
| SE0303541D0 (sv) | 2003-12-22 | 2003-12-22 | Astrazeneca Ab | New compounds |
| JP2007522129A (ja) | 2004-01-21 | 2007-08-09 | エラン ファーマシューティカルズ，インコーポレイテッド | アスパラギン酸プロテアーゼ阻害薬を用いるアミロイドーシスの処置方法 |
| EP1745019A1 (en) | 2004-05-06 | 2007-01-24 | Pfizer Inc. | Novel compounds of proline and morpholine derivatives |
| TWI350168B (en) | 2004-05-07 | 2011-10-11 | Incyte Corp | Amido compounds and their use as pharmaceuticals |
| CA2589565A1 (en) | 2004-06-24 | 2006-01-05 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| BRPI0512410A (pt) | 2004-06-24 | 2008-03-04 | Incyte Corp | compostos de amido e seu uso como produtos farmacêuticos |
| AU2005267331A1 (en) | 2004-06-24 | 2006-02-02 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| EP1768954A4 (en) | 2004-06-24 | 2008-05-28 | Incyte Corp | 2-METHYLPROPANAMIDES AND THEIR USE AS PHARMACEUTICALS |
| EP1773780A4 (en) | 2004-06-24 | 2008-01-09 | Incyte Corp | AMIDO COMPOUNDS AND USES THEREOF AS PHARMACEUTICAL PRODUCTS |
| BRPI0512535A (pt) | 2004-06-24 | 2008-03-25 | Incyte Corp | compostos de piperidinas n-substituìdas, suas composições e métodos de modulações |
| AU2005273986A1 (en) | 2004-08-10 | 2006-02-23 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| WO2006047176A1 (en) | 2004-10-22 | 2006-05-04 | Cargill, Incorporated | Process for the production of maltodextrins and maltodextrins |
| AU2005304560C1 (en) | 2004-11-10 | 2013-05-09 | Incyte Holdings Corporation | Lactam compounds and their use as pharmaceuticals |
| EP1833836B1 (en) | 2004-11-12 | 2011-12-21 | Bristol-Myers Squibb Company | Imidazo-fused thiazolo [4,5-b] pyridine based tricyclic compounds and pharmaceutical compositions comprising same |
| CN101103016A (zh) | 2004-11-18 | 2008-01-09 | 因塞特公司 | 11-β羟基类固醇脱氢酶1型抑制剂及其使用方法 |
| CN102816081A (zh) | 2005-01-05 | 2012-12-12 | 雅培制药有限公司 | 11-β-羟甾类脱氢酶1型酶的抑制剂 |
| KR100979577B1 (ko) | 2005-03-03 | 2010-09-01 | 에프. 호프만-라 로슈 아게 | 2형 진성 당뇨병의 치료를 위한11-베타-하이드록시스테로이드 탈수소효소의 억제제로서1-설폰일-피페리딘-3-카복실산 아마이드 유도체 |
| CA2621255A1 (en) | 2005-09-21 | 2007-04-05 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| AU2006322060A1 (en) | 2005-12-05 | 2007-06-14 | Incyte Corporation | Lactam compounds and methods of using the same |
| WO2007084314A2 (en) | 2006-01-12 | 2007-07-26 | Incyte Corporation | MODULATORS OF 11-ß HYDROXYL STEROID DEHYDROGENASE TYPE 1, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USING THE SAME |
| BRPI0707408A2 (pt) | 2006-01-31 | 2011-05-03 | Incyte Corp | compostos de amido e seu uso como produtos farmacêuticos |
| JP2007219880A (ja) * | 2006-02-17 | 2007-08-30 | Fujitsu Ltd | 評判情報処理プログラム、方法及び装置 |
| WO2007101270A1 (en) | 2006-03-02 | 2007-09-07 | Incyte Corporation | MODULATORS OF 11-β HYDROXYL STEROID DEHYDROGENASE TYPE 1, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USING THE SAME |
| US20070208001A1 (en) | 2006-03-03 | 2007-09-06 | Jincong Zhuo | Modulators of 11- beta hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same |
| US20070293529A1 (en) | 2006-05-01 | 2007-12-20 | Yun-Long Li | Tetrasubstituted ureas as modulators of 11-beta hydroxyl steroid dehydrogenase type 1 |
| US7838544B2 (en) | 2006-05-17 | 2010-11-23 | Incyte Corporation | Heterocyclic inhibitors of 11-β hydroxyl steroid dehydrogenase type 1 and methods of using the same |
| CL2008001839A1 (es) | 2007-06-21 | 2009-01-16 | Incyte Holdings Corp | Compuestos derivados de 2,7-diazaespirociclos, inhibidores de 11-beta hidroxil esteroide deshidrogenasa tipo 1; composicion farmaceutica que comprende a dichos compuestos; utiles para tratar la obesidad, diabetes, intolerancia a la glucosa, diabetes tipo ii, entre otras enfermedades. |
-
2005
- 2005-06-23 BR BRPI0512535-9A patent/BRPI0512535A/pt not_active IP Right Cessation
- 2005-06-23 CA CA002570637A patent/CA2570637A1/en not_active Abandoned
- 2005-06-23 JP JP2007518277A patent/JP2008504275A/ja active Pending
- 2005-06-23 EA EA200700117A patent/EA200700117A1/ru unknown
- 2005-06-23 EP EP05763380A patent/EP1758580A4/en not_active Withdrawn
- 2005-06-23 US US11/159,448 patent/US8071624B2/en active Active
- 2005-06-23 AU AU2005267289A patent/AU2005267289A1/en not_active Abandoned
- 2005-06-23 WO PCT/US2005/022307 patent/WO2006012226A2/en not_active Ceased
- 2005-06-23 NZ NZ551603A patent/NZ551603A/en not_active IP Right Cessation
- 2005-06-23 MX MXPA06014574A patent/MXPA06014574A/es not_active Application Discontinuation
-
2006
- 2006-11-23 IL IL179520A patent/IL179520A0/en unknown
- 2006-12-06 CR CR8793A patent/CR8793A/es unknown
- 2006-12-26 EC EC2006007114A patent/ECSP067114A/es unknown
-
2011
- 2011-10-24 US US13/279,700 patent/US8288417B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| IL179520A0 (en) | 2007-05-15 |
| BRPI0512535A (pt) | 2008-03-25 |
| EA200700117A1 (ru) | 2007-06-29 |
| US20120040964A1 (en) | 2012-02-16 |
| WO2006012226A2 (en) | 2006-02-02 |
| CA2570637A1 (en) | 2006-02-02 |
| US8288417B2 (en) | 2012-10-16 |
| EP1758580A4 (en) | 2008-01-16 |
| US20060004049A1 (en) | 2006-01-05 |
| JP2008504275A (ja) | 2008-02-14 |
| CR8793A (es) | 2007-08-28 |
| ECSP067114A (es) | 2007-01-26 |
| US8071624B2 (en) | 2011-12-06 |
| WO2006012226A3 (en) | 2006-07-27 |
| AU2005267289A1 (en) | 2006-02-02 |
| EP1758580A2 (en) | 2007-03-07 |
| NZ551603A (en) | 2010-11-26 |
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