PT1537078E - Indoles que possuem actividade antidiabética - Google Patents
Indoles que possuem actividade antidiabética Download PDFInfo
- Publication number
- PT1537078E PT1537078E PT03791952T PT03791952T PT1537078E PT 1537078 E PT1537078 E PT 1537078E PT 03791952 T PT03791952 T PT 03791952T PT 03791952 T PT03791952 T PT 03791952T PT 1537078 E PT1537078 E PT 1537078E
- Authority
- PT
- Portugal
- Prior art keywords
- methyl
- indol
- trifluoromethoxy
- phenoxy
- acid
- Prior art date
Links
- 230000003178 anti-diabetic effect Effects 0.000 title description 2
- 150000002475 indoles Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 334
- -1 - O- (C2 -C5) alkyl Chemical group 0.000 claims description 282
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 197
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 claims description 141
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 141
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 claims description 116
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 94
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 71
- 235000019260 propionic acid Nutrition 0.000 claims description 71
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 57
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 57
- 238000011282 treatment Methods 0.000 claims description 54
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 52
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 46
- 125000005843 halogen group Chemical group 0.000 claims description 44
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 38
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 37
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 37
- 239000000556 agonist Substances 0.000 claims description 36
- 229910052736 halogen Inorganic materials 0.000 claims description 34
- 150000002367 halogens Chemical class 0.000 claims description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- 229940125396 insulin Drugs 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 29
- 102000004877 Insulin Human genes 0.000 claims description 28
- 108090001061 Insulin Proteins 0.000 claims description 28
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims description 28
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 24
- 239000003112 inhibitor Substances 0.000 claims description 22
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 21
- 239000008103 glucose Substances 0.000 claims description 20
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 19
- 108010016731 PPAR gamma Proteins 0.000 claims description 19
- LIZRTJPNVJDDNR-UHFFFAOYSA-N 3-methyl-2-[3-[[2-methyl-6-(trifluoromethoxy)-3-[4-(trifluoromethoxy)benzoyl]indol-1-yl]methyl]phenoxy]butanoic acid Chemical compound CC(C)C(C(O)=O)OC1=CC=CC(CN2C3=CC(OC(F)(F)F)=CC=C3C(C(=O)C=3C=CC(OC(F)(F)F)=CC=3)=C2C)=C1 LIZRTJPNVJDDNR-UHFFFAOYSA-N 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 201000001320 Atherosclerosis Diseases 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 102000023984 PPAR alpha Human genes 0.000 claims description 16
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 15
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 claims description 15
- 206010022489 Insulin Resistance Diseases 0.000 claims description 14
- 208000035475 disorder Diseases 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 201000001421 hyperglycemia Diseases 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 11
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 11
- 150000002632 lipids Chemical class 0.000 claims description 11
- 230000002829 reductive effect Effects 0.000 claims description 11
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 10
- 150000001721 carbon Chemical group 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 208000008589 Obesity Diseases 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 235000020824 obesity Nutrition 0.000 claims description 9
- 239000004031 partial agonist Substances 0.000 claims description 9
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 8
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 8
- 108010010234 HDL Lipoproteins Proteins 0.000 claims description 8
- 102000015779 HDL Lipoproteins Human genes 0.000 claims description 8
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 8
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 125000002950 monocyclic group Chemical group 0.000 claims description 8
- 229940123208 Biguanide Drugs 0.000 claims description 7
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 7
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 7
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 7
- 150000004283 biguanides Chemical class 0.000 claims description 7
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 7
- OVBFMEVBMNZIBR-UHFFFAOYSA-N -2-Methylpentanoic acid Natural products CCCC(C)C(O)=O OVBFMEVBMNZIBR-UHFFFAOYSA-N 0.000 claims description 6
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000002619 bicyclic group Chemical group 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 5
- 229940100389 Sulfonylurea Drugs 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 230000036961 partial effect Effects 0.000 claims description 5
- 150000003536 tetrazoles Chemical class 0.000 claims description 5
- MVQVNTPHUGQQHK-UHFFFAOYSA-N 3-pyridinemethanol Chemical compound OCC1=CC=CN=C1 MVQVNTPHUGQQHK-UHFFFAOYSA-N 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 230000003579 anti-obesity Effects 0.000 claims description 4
- 229920000080 bile acid sequestrant Polymers 0.000 claims description 4
- 229940096699 bile acid sequestrants Drugs 0.000 claims description 4
- 230000001906 cholesterol absorption Effects 0.000 claims description 4
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 claims description 4
- 230000009977 dual effect Effects 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 230000002792 vascular Effects 0.000 claims description 4
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 claims description 3
- STXANKVKGVTYTM-UHFFFAOYSA-N 2-[3-[[3-(4-chlorophenyl)-2-methyl-6-(trifluoromethyl)indol-1-yl]methyl]phenoxy]butanoic acid Chemical compound CCC(C(O)=O)OC1=CC=CC(CN2C3=CC(=CC=C3C(C=3C=CC(Cl)=CC=3)=C2C)C(F)(F)F)=C1 STXANKVKGVTYTM-UHFFFAOYSA-N 0.000 claims description 3
- 208000004611 Abdominal Obesity Diseases 0.000 claims description 3
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 claims description 3
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 3
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 3
- 206010065941 Central obesity Diseases 0.000 claims description 3
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
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- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims description 3
- 229940122904 Glucagon receptor antagonist Drugs 0.000 claims description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 3
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 3
- 206010036049 Polycystic ovaries Diseases 0.000 claims description 3
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 3
- 102100040918 Pro-glucagon Human genes 0.000 claims description 3
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- 206010038923 Retinopathy Diseases 0.000 claims description 3
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 3
- 102000001494 Sterol O-Acyltransferase Human genes 0.000 claims description 3
- 108010054082 Sterol O-acyltransferase Proteins 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 239000003888 alpha glucosidase inhibitor Substances 0.000 claims description 3
- 229960005370 atorvastatin Drugs 0.000 claims description 3
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 108091022863 bile acid binding Proteins 0.000 claims description 3
- 102000030904 bile acid binding Human genes 0.000 claims description 3
- GPUADMRJQVPIAS-QCVDVZFFSA-M cerivastatin sodium Chemical compound [Na+].COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 GPUADMRJQVPIAS-QCVDVZFFSA-M 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 229960003765 fluvastatin Drugs 0.000 claims description 3
- 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 claims description 3
- 229960004844 lovastatin Drugs 0.000 claims description 3
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 3
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 3
- 229960003512 nicotinic acid Drugs 0.000 claims description 3
- 235000001968 nicotinic acid Nutrition 0.000 claims description 3
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- 239000002530 phenolic antioxidant Substances 0.000 claims description 3
- 229960002797 pitavastatin Drugs 0.000 claims description 3
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 claims description 3
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 3
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- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 3
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- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- 229960000672 rosuvastatin Drugs 0.000 claims description 3
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 3
- LALFOYNTGMUKGG-BGRFNVSISA-L rosuvastatin calcium Chemical compound [Ca+2].CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O.CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O LALFOYNTGMUKGG-BGRFNVSISA-L 0.000 claims description 3
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- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 3
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- NCNVNURXIBVECA-INIZCTEOSA-N (4-chlorophenyl)-[2-methyl-1-[[3-[(1s)-1-(2h-tetrazol-5-yl)ethoxy]phenyl]methyl]-6-(trifluoromethoxy)indol-3-yl]methanone Chemical compound O([C@@H](C)C1=NNN=N1)C(C=1)=CC=CC=1CN(C1=CC(OC(F)(F)F)=CC=C11)C(C)=C1C(=O)C1=CC=C(Cl)C=C1 NCNVNURXIBVECA-INIZCTEOSA-N 0.000 claims description 2
- 125000006531 (C2-C5) alkyl group Chemical group 0.000 claims description 2
- LWCDJIZVNNXFPJ-UHFFFAOYSA-N 2-[3-[[3-(4-chlorophenoxy)-6-fluoro-2-methylindol-1-yl]methyl]phenoxy]butanoic acid Chemical compound CCC(C(O)=O)OC1=CC=CC(CN2C3=CC(F)=CC=C3C(OC=3C=CC(Cl)=CC=3)=C2C)=C1 LWCDJIZVNNXFPJ-UHFFFAOYSA-N 0.000 claims description 2
- HBSUETPUJSVLGL-UHFFFAOYSA-N 2-[6-[3-(4-chlorobenzoyl)-2-methyl-6-(trifluoromethoxy)indol-1-yl]pyridin-2-yl]oxy-2-methylpropanoic acid Chemical compound C12=CC=C(OC(F)(F)F)C=C2N(C=2N=C(OC(C)(C)C(O)=O)C=CC=2)C(C)=C1C(=O)C1=CC=C(Cl)C=C1 HBSUETPUJSVLGL-UHFFFAOYSA-N 0.000 claims description 2
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- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
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- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 210000001672 ovary Anatomy 0.000 claims description 2
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- NISPZHOPXCGOEX-SFHVURJKSA-N (2s)-2-[3-[[3-(4-methoxy-2-methylbenzoyl)-2-methyl-6-(trifluoromethoxy)indol-1-yl]methyl]phenoxy]propanoic acid Chemical compound CC1=CC(OC)=CC=C1C(=O)C(C1=CC=C(OC(F)(F)F)C=C11)=C(C)N1CC1=CC=CC(O[C@@H](C)C(O)=O)=C1 NISPZHOPXCGOEX-SFHVURJKSA-N 0.000 claims 17
- LOPXRVSGPQAMQP-UHFFFAOYSA-N 2-[5-[3-(4-chlorobenzoyl)-2-methyl-6-(trifluoromethoxy)indol-1-yl]-2-fluorophenoxy]-2-methylpropanoic acid Chemical compound C12=CC=C(OC(F)(F)F)C=C2N(C=2C=C(OC(C)(C)C(O)=O)C(F)=CC=2)C(C)=C1C(=O)C1=CC=C(Cl)C=C1 LOPXRVSGPQAMQP-UHFFFAOYSA-N 0.000 claims 15
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 claims 4
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- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- C07D209/04—Indoles; Hydrogenated indoles
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- C07D209/32—Oxygen atoms
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- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
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- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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Families Citing this family (137)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2495915A1 (en) * | 2002-08-29 | 2004-03-11 | Merck & Co., Inc. | Indoles having anti-diabetic activity |
| CA2495943C (en) * | 2002-08-29 | 2009-07-21 | Merck & Co., Inc. | Indoles having anti-diabetic activity |
| BRPI0406761A (pt) | 2003-01-14 | 2005-12-20 | Arena Pharm Inc | Derivados de arila e heteroarila 1,2,3-trissubstituìdos como moduladores do metabolismo e a profilaxia e tratamento de distúrbios relacionados a estes tais como diabetes e hiper-glicemia |
| EA200501607A1 (ru) * | 2003-04-14 | 2006-06-30 | ДЗЕ ИНСТИТЬЮТС ФОР ФАРМАСЬЮТИКАЛ ДИСКАВЕРИ, ЭлЭлСи | Замещённые фенилалкановые кислоты |
| KR20060006953A (ko) | 2003-04-30 | 2006-01-20 | 디 인스티튜트스 포 파마슈티컬 디스커버리, 엘엘씨 | 치환된 카르복실산 |
| AR045697A1 (es) | 2003-07-14 | 2005-11-09 | Arena Pharm Inc | Aril y heteroaril derivados fusionados como moduladores del metabolismo y la prevencion y tratamiento de trastornos relacionados con el mismo |
| CN101031289A (zh) * | 2004-04-26 | 2007-09-05 | 范德比尔特大学 | 作为具有降低胃肠毒性的治疗剂的吲哚乙酸和茚乙酸衍生物 |
| WO2005105785A2 (en) * | 2004-05-04 | 2005-11-10 | Novo Nordisk A/S | Indole derivatives for treatment of obesity |
| US20080076810A1 (en) * | 2004-05-28 | 2008-03-27 | Weiguo Lui | Benzoureas Having Anti-Diabetic Activity |
| US8022063B2 (en) * | 2004-05-29 | 2011-09-20 | 7Tm Pharma A/S | CRTH2 receptor ligands for medicinal uses |
| EP1765329A2 (en) | 2004-07-02 | 2007-03-28 | Merck & Co., Inc. | Indoles having anti-diabetic activity |
| CA2574021A1 (en) | 2004-07-30 | 2006-02-02 | Carmen Serra Comas | Tyrosine derivatives as ppar-gamma-modulators |
| US20060135540A1 (en) * | 2004-11-30 | 2006-06-22 | Jack Lin | PPAR active compounds |
| MY148521A (en) | 2005-01-10 | 2013-04-30 | Arena Pharm Inc | Substituted pyridinyl and pyrimidinyl derivatives as modulators of metabolism and the treatment of disorders related thereto |
| WO2006075638A1 (ja) * | 2005-01-14 | 2006-07-20 | Dainippon Sumitomo Pharma Co., Ltd. | 新規ヘテロアリール誘導体 |
| ZA200705827B (en) * | 2005-01-19 | 2008-10-29 | Biolipox Ab | Indoles useful in the treatment of inflammation |
| US7538242B2 (en) | 2005-03-01 | 2009-05-26 | Kowa Co., Ltd. | Optically active PPAR-activating compound intermediate and method for producing same |
| BRPI0609352A2 (pt) | 2005-03-04 | 2011-10-18 | Merck & Co Inc | composto ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, uso de um composto ou um sal farmaceuticamente aceitável do mesmo, e, métodos para tratar uma ou mais doenças, distúrbios ou condições, e para tratar diabetes melito não dependentes da insulina (tipo 2) em um paciente |
| CA2599710A1 (en) | 2005-03-10 | 2006-09-21 | Merck & Co., Inc. | Novel crystalline forms of antidiabetic compounds |
| MX2008003202A (es) * | 2005-09-16 | 2008-03-25 | Serenex Inc | Derivados de carbazol. |
| US8399666B2 (en) | 2005-11-04 | 2013-03-19 | Panmira Pharmaceuticals, Llc | 5-lipoxygenase-activating protein (FLAP) inhibitors |
| US7977359B2 (en) | 2005-11-04 | 2011-07-12 | Amira Pharmaceuticals, Inc. | 5-lipdxygenase-activating protein (FLAP) inhibitors |
| GB2431927B (en) | 2005-11-04 | 2010-03-17 | Amira Pharmaceuticals Inc | 5-Lipoxygenase-activating protein (FLAP) inhibitors |
| CA2657691A1 (en) | 2006-06-19 | 2007-12-27 | Vanderbilt University | Methods and compositions for diagnostic and therapeutic targeting of cox-2 |
| TW200821284A (en) * | 2006-10-03 | 2008-05-16 | Merck & Co Inc | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
| WO2008089581A1 (en) | 2007-01-26 | 2008-07-31 | Merck Frosst Canada Ltd. | Fused aromatic ptp-1b inhibitors |
| PE20090159A1 (es) | 2007-03-08 | 2009-02-21 | Plexxikon Inc | COMPUESTOS DERIVADOS DE ACIDO INDOL-PROPIONICO COMO MODULADORES PPARs |
| WO2008137105A1 (en) | 2007-05-07 | 2008-11-13 | Merck & Co., Inc. | Method of treatment using fused aromatic compounds having anti-diabetic activity |
| RU2361581C2 (ru) * | 2007-09-14 | 2009-07-20 | Закрытое Акционерное Общество "Мастерклон" | Фармацевтическая композиция, обладающая противодиабетической, гиполипидемической, гипогликемической и гипохолестеринемической активностью, способ ее получения и способы лечения указанных заболеваний |
| TW200920369A (en) | 2007-10-26 | 2009-05-16 | Amira Pharmaceuticals Inc | 5-lipoxygenase activating protein (flap) inhibitor |
| JP5791500B2 (ja) | 2008-05-23 | 2015-10-07 | パンミラ ファーマシューティカルズ,エルエルシー. | 5−リポキシゲナーゼ活性化タンパク質阻害剤 |
| WO2010001869A1 (ja) * | 2008-06-30 | 2010-01-07 | 武田薬品工業株式会社 | 4置換ベンゼン化合物およびその用途 |
| TWI614024B (zh) * | 2008-08-11 | 2018-02-11 | 曼凱公司 | 超快起作用胰島素之用途 |
| US8546431B2 (en) | 2008-10-01 | 2013-10-01 | Panmira Pharmaceuticals, Llc | 5-lipoxygenase-activating protein (FLAP) inhibitors |
| JO2870B1 (en) | 2008-11-13 | 2015-03-15 | ميرك شارب اند دوهم كورب | Amino Tetra Hydro Pirans as Inhibitors of Peptide Dipeptide IV for the Treatment or Prevention of Diabetes |
| WO2010056717A1 (en) | 2008-11-17 | 2010-05-20 | Merck Sharp & Dohme Corp. | Substituted bicyclic amines for the treatment of diabetes |
| RU2408579C2 (ru) * | 2008-12-31 | 2011-01-10 | Федеральное государственное образовательное учреждение высшего профессионального образования "ЮЖНЫЙ ФЕДЕРАЛЬНЫЙ УНИВЕРСИТЕТ" (ЮФУ) | Гидрогалогениды n-[2-(1-алкил-1н-индол-3-ил)-1-(4-алкилпиперазин-1-карбонил)винил]-2-фторбензамида, обладающие местноанестезирующей и антиаритмической активностью |
| TW201028414A (en) | 2009-01-16 | 2010-08-01 | Merck Sharp & Dohme | Oxadiazole beta carboline derivatives as antidiabetic compounds |
| EP2389226B1 (en) | 2009-01-23 | 2013-11-20 | Merck Sharp & Dohme Corp. | Bridged and fused heterocyclic antidiabetic compounds |
| CA2749891A1 (en) | 2009-01-23 | 2010-07-29 | Hubert B. Josien | Bridged and fused antidiabetic compounds |
| EP2393810A1 (en) | 2009-02-05 | 2011-12-14 | Schering Corporation | Phthalazine-containing antidiabetic compounds |
| WO2011011508A1 (en) | 2009-07-23 | 2011-01-27 | Schering Corporation | Benzo-fused oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors |
| WO2011011506A1 (en) | 2009-07-23 | 2011-01-27 | Schering Corporation | Spirocyclic oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors |
| WO2011019538A1 (en) | 2009-08-13 | 2011-02-17 | Merck Sharp & Dohme Corp. | Substituted cyclopropyl compounds, compositions containing such compounds and methods of treatment |
| IN2012DN00721A (enExample) | 2009-09-02 | 2015-06-19 | Merck Sharp & Dohme | |
| CN102695414A (zh) | 2010-01-15 | 2012-09-26 | 默沙东公司 | 作为抗糖尿病化合物的噁二唑β-咔啉衍生物 |
| RU2012136451A (ru) | 2010-01-28 | 2014-03-10 | Президент Энд Феллоуз Оф Гарвард Колледж | Композиции и способы улучшения активности протеасомы |
| EP2538783B1 (en) | 2010-02-22 | 2016-06-01 | Merck Sharp & Dohme Corp. | Substituted aminotetrahydrothiopyrans and derivatives thereof as dipeptidyl peptidase-iv inhibitors for the treatment of diabetes |
| JP2013100235A (ja) * | 2010-03-08 | 2013-05-23 | Dainippon Sumitomo Pharma Co Ltd | 新規インドール誘導体 |
| US8785634B2 (en) | 2010-04-26 | 2014-07-22 | Merck Sharp & Dohme Corp | Spiropiperidine prolylcarboxypeptidase inhibitors |
| US9365539B2 (en) | 2010-05-11 | 2016-06-14 | Merck Sharp & Dohme Corp. | Prolylcarboxypeptidase inhibitors |
| EP2571876B1 (en) | 2010-05-21 | 2016-09-07 | Merck Sharp & Dohme Corp. | Substituted seven-membered heterocyclic compounds as dipeptidyl peptidase-iv inhibitors for the treatment of diabetes |
| WO2011156246A1 (en) | 2010-06-11 | 2011-12-15 | Merck Sharp & Dohme Corp. | Novel prolylcarboxypeptidase inhibitors |
| WO2012024183A1 (en) | 2010-08-18 | 2012-02-23 | Merck Sharp & Dohme Corp. | Spiroxazolidinone compounds |
| CN103201262B (zh) | 2010-08-20 | 2016-06-01 | 艾米拉医药股份有限公司 | 自分泌运动因子抑制剂及其用途 |
| SG188548A1 (en) | 2010-09-22 | 2013-04-30 | Arena Pharm Inc | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| MX2013004739A (es) | 2010-10-29 | 2013-07-02 | Merck Sharp & Dohme | Derivados heterociclicos de diazenodiolato. |
| AU2012208837B2 (en) | 2011-01-20 | 2016-07-28 | Merck Sharp & Dohme Corp. | Mineralocorticoid receptor antagonists |
| JO3350B1 (ar) | 2011-03-07 | 2019-03-13 | Merck Sharp & Dohme | مشتقات حلقية غير متجانسة محتوية على مجموعات أمينو أولية ومركبات داي أزينيومديولات |
| US8957062B2 (en) | 2011-04-08 | 2015-02-17 | Merck Sharp & Dohme Corp. | Substituted cyclopropyl compounds, compositions containing such compounds and methods of treatment |
| WO2012139495A1 (en) | 2011-04-13 | 2012-10-18 | Merck Sharp & Dohme Corp. | Mineralocorticoid receptor antagonists |
| US9272987B2 (en) | 2011-05-02 | 2016-03-01 | Merck Sharp & Dohme Corp. | Diazeniumdiolate cyclohexyl derivatives |
| JP6208122B2 (ja) | 2011-05-12 | 2017-10-04 | プロテオステイシス セラピューティクス,インコーポレイテッド | プロテオスタシス調節因子 |
| EP2714680B1 (en) | 2011-05-27 | 2015-11-25 | Amira Pharmaceuticals, Inc. | Heterocyclic autotaxin inhibitors and uses thereof |
| US20140088124A1 (en) | 2011-06-02 | 2014-03-27 | Robert J. DeVita | Imidazole derivatives |
| WO2012173917A1 (en) | 2011-06-16 | 2012-12-20 | Merck Sharp & Dohme Corp. | Substituted cyclopropyl compounds, compositions containing such compounds, and methods of treatment |
| EP2760855B1 (en) | 2011-09-30 | 2017-03-15 | Merck Sharp & Dohme Corp. | Substituted cyclopropyl compounds, compositions containing such compounds as well as their use in treating type-2 diabetes |
| US9505730B2 (en) | 2011-10-13 | 2016-11-29 | Merck Sharp & Dohme Corp. | Mineralocorticoid receptor antagonists |
| EP3078374B1 (en) | 2011-10-17 | 2019-06-19 | Vanderbilt University | Indomethacin analogs for the treatment of castrate-resistant prostate cancer |
| US9018200B2 (en) | 2011-10-24 | 2015-04-28 | Merck Sharp & Dohme Corp. | Substituted piperidinyl compounds useful as GPR119 agonists |
| JO3210B1 (ar) | 2011-10-28 | 2018-03-08 | Merck Sharp & Dohme | مثبط منصهر لبروتين نقل الكوليسترليستير اوكسازوليدينون ثمائي الحلقة |
| WO2013068328A1 (en) | 2011-11-07 | 2013-05-16 | Intervet International B.V. | Bicyclo [2.2.2] octan-1-ylcarboxylic acid compounds as dgat-1 inhibitors |
| WO2013068439A1 (en) | 2011-11-09 | 2013-05-16 | Intervet International B.V. | 4-amino-5-oxo-7,8-dihydropyrimido[5, 4 -f] [1, 4] oxazepine compounds as dgat1 inhibitors |
| US9018224B2 (en) | 2011-11-15 | 2015-04-28 | Merck Sharp & Dohme Corp. | Substituted cyclopropyl compounds useful as GPR119 agonists |
| WO2013122920A1 (en) | 2012-02-17 | 2013-08-22 | Merck Sharp & Dohme Corp. | Dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes |
| JP2015516965A (ja) * | 2012-04-03 | 2015-06-18 | アポセンス リミテッドAposense Ltd. | 診断指標及び治療指標のための新規な標的指向性薬剤 |
| CA2870488A1 (en) | 2012-04-16 | 2013-10-24 | Kaneq Pharma Inc. | Fused aromatic phosphonate derivatives as precursors to ptp-1b inhibitors |
| EP2874622A4 (en) | 2012-07-23 | 2015-12-30 | Merck Sharp & Dohme | TREATMENT OF DIABETES WITH DIPEPTIDYLPEPTIDASE IV INHIBITORS |
| US9453038B2 (en) | 2012-12-17 | 2016-09-27 | Merck Sharp & Dohme Corp. | Glucokinase activator compounds, compositions containing such compounds, and methods of treatment |
| EP2934518B1 (en) | 2012-12-19 | 2020-02-19 | Merck Sharp & Dohme Corp. | Spirocyclic cetp inhibitors |
| US9849135B2 (en) | 2013-01-25 | 2017-12-26 | President And Fellows Of Harvard College | USP14 inhibitors for treating or preventing viral infections |
| JP2016530209A (ja) | 2013-09-17 | 2016-09-29 | ファーマケア,インク. | ビニルオートタキシン阻害剤化合物 |
| US9951026B2 (en) | 2013-09-17 | 2018-04-24 | Pharmakea, Inc. | Heterocyclic vinyl autotaxin inhibitor compounds |
| EP3049405A4 (en) | 2013-09-26 | 2017-03-08 | Pharmakea Inc. | Autotaxin inhibitor compounds |
| WO2015051496A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| WO2015073528A1 (en) | 2013-11-12 | 2015-05-21 | Proteostasis Therapeutics, Inc. | Proteasome activity enhancing compounds |
| KR102515248B1 (ko) | 2013-11-22 | 2023-03-29 | 사브레 테라퓨틱스 엘엘씨 | 오토탁신 억제제 화합물 |
| WO2015089809A1 (en) | 2013-12-19 | 2015-06-25 | Merck Sharp & Dohme Corp. | Antidiabetic substituted heteroaryl compounds |
| WO2015112465A1 (en) | 2014-01-24 | 2015-07-30 | Merck Sharp & Dohme Corp. | Isoquinoline derivatives as mgat2 inhibitors |
| KR102471082B1 (ko) * | 2014-05-20 | 2022-11-25 | 라퀄리아 파마 인코포레이티드 | 벤즈이소옥사졸 유도체염 |
| WO2015176267A1 (en) | 2014-05-22 | 2015-11-26 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| EP3174537B1 (en) | 2014-07-29 | 2021-06-23 | Merck Sharp & Dohme Corp. | Monocyclic isoxazolines as inhibitors of cholesterol ester transfer protein |
| WO2016022448A1 (en) | 2014-08-08 | 2016-02-11 | Merck Sharp & Dohme Corp. | Antidiabetic bicyclic compounds |
| US10100042B2 (en) | 2014-08-08 | 2018-10-16 | Merck Sharp & Dohme Corp. | [5,6]—fused bicyclic antidiabetic compounds |
| WO2016022742A1 (en) | 2014-08-08 | 2016-02-11 | Merck Sharp & Dohme Corp. | Antidiabetic bicyclic compounds |
| CA2964379C (en) | 2014-10-24 | 2023-08-15 | Merck Sharp & Dohme Corp. | Co-agonists of the glucagon and glp-1 receptors |
| TW201625635A (zh) | 2014-11-21 | 2016-07-16 | 默沙東藥廠 | 作為可溶性鳥苷酸環化酶活化劑之三唑并吡基衍生物 |
| AU2016205361C1 (en) | 2015-01-06 | 2021-04-08 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the S1P1 receptor |
| EA039684B1 (ru) | 2015-05-27 | 2022-02-28 | Сабре Терапьютикс Ллс | Ингибиторы аутотаксина и их применения |
| WO2016191334A1 (en) | 2015-05-27 | 2016-12-01 | Merck Sharp & Dohme Corp. | Imidazo-pyrazinyl derivatives useful as soluble guanylate cyclase activators |
| US10213429B2 (en) | 2015-05-28 | 2019-02-26 | Merck Sharp & Dohme Corp. | Imidazo-pyrazinyl derivatives useful as soluble guanylate cyclase activators |
| CA3002551A1 (en) | 2015-06-22 | 2016-12-29 | Arena Pharmaceuticals, Inc. | Crystalline l-arginine salt of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl)acetic acid(com pound 1)for use in s1p1 receptor-associated disorders |
| US20180230166A1 (en) | 2015-07-13 | 2018-08-16 | Merck Sharp & Dohme Corp. | Bicyclic heterocycles as inhibitors of cholesterol ester transfer protein |
| WO2017062334A1 (en) | 2015-10-05 | 2017-04-13 | Merck Sharp & Dohme Corp. | Antibody peptide conjugates that have agonist activity at both the glucagon and glucagon-like peptide 1 receptors |
| CN113004205B (zh) * | 2015-10-07 | 2024-07-02 | 米托布里奇公司 | Ppar激动剂、化合物、药物组合物及其使用方法 |
| US10450309B2 (en) | 2015-11-30 | 2019-10-22 | Merch Sharp & Dohme Corp. | Aryl sulfonamides as BLT1 antagonists |
| EP3383868B1 (en) | 2015-11-30 | 2022-10-05 | Merck Sharp & Dohme LLC | Aryl sulfonamides as blt1 antagonists |
| WO2017107052A1 (en) | 2015-12-22 | 2017-06-29 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase stimulators |
| CN107286158A (zh) * | 2016-03-30 | 2017-10-24 | 中国科学院上海药物研究所 | 苯基[a]吲哚[2,3-g]并喹嗪类化合物、其制备方法、药物组合物及其应用 |
| ES2861503T3 (es) | 2016-04-13 | 2021-10-06 | Mitobridge Inc | Agonistas de PPAR, compuestos, composiciones farmacéuticas y métodos de uso de los mismos |
| WO2017197555A1 (en) | 2016-05-16 | 2017-11-23 | Merck Sharp & Dohme Corp. | Fused pyrazine derivatives useful as soluble guanylate cyclase stimulators |
| WO2017201683A1 (en) | 2016-05-25 | 2017-11-30 | Merck Sharp & Dohme Corp. | Substituted tetrahydroisoquinoline compounds useful as gpr120 agonists |
| US10414774B2 (en) | 2016-08-15 | 2019-09-17 | Merck Sharp & Dohme Corp. | Compound useful for altering the levels of bile acids for the treatment of diabetes and cardiometabolc disease |
| EP3496715B1 (en) | 2016-08-15 | 2021-11-03 | Merck Sharp & Dohme Corp. | Compounds useful for altering the levels of bile acids for the treatment of diabetes and cardiometabolic disease |
| WO2018057409A1 (en) | 2016-09-20 | 2018-03-29 | Merck Sharp & Dohme Corp. | Substituted 1-methyl-1,2,3,4-tetrahydroisoquinoline molecules as pcsk9 allosteric binders |
| RU2019117958A (ru) | 2016-11-18 | 2020-12-18 | Мерк Шарп И Доум Корп. | Производные индола, полезные в качестве ингибиторов диацилглицерид-о-ацилтрансферазы 2 |
| CA3043203A1 (en) | 2016-11-18 | 2018-05-24 | Merck Sharp & Dohme Corp. | Indazole derivatives useful as inhibitors of diacylglyceride o-acyltransferase 2 |
| WO2018107415A1 (en) | 2016-12-15 | 2018-06-21 | Merck Sharp & Dohme Corp. | Hydroxy isoxazole compounds useful as gpr120 agonists |
| CA3053418A1 (en) | 2017-02-16 | 2018-08-23 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of primary biliary cholangitis |
| CA3102136A1 (en) | 2018-06-06 | 2019-12-12 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the s1p1 receptor |
| JOP20190150A1 (ar) | 2018-06-21 | 2019-12-21 | Merck Sharp & Dohme | مركبات مناهضة لـ pcsk9 |
| WO2020205688A1 (en) | 2019-04-04 | 2020-10-08 | Merck Sharp & Dohme Corp. | Inhibitors of histone deacetylase-3 useful for the treatment of cancer, inflammation, neurodegeneration diseases and diabetes |
| WO2020236688A1 (en) | 2019-05-22 | 2020-11-26 | Merck Sharp & Dohme Corp. | Natriuretic peptide receptor a agonists useful for the treatment of cardiometabolic diseases, kidney disease and diabetes |
| US20220281886A1 (en) | 2019-05-22 | 2022-09-08 | Merck Sharp Dohme Corp. | Natriuretic peptide receptor a agonists useful for the treatment of cardiometabolic diseases, kidney disease and diabetes |
| TW202123960A (zh) | 2019-08-30 | 2021-07-01 | 美商默沙東藥廠 | Pcsk9拮抗劑化合物 |
| EP3842060A1 (en) | 2019-12-23 | 2021-06-30 | Merck Sharp & Dohme Corp. | Stapled lactam co-agonists of the glucagon and glp-1 receptors |
| EP3842061A1 (en) | 2019-12-23 | 2021-06-30 | Merck Sharp & Dohme Corp. | Stapled triazole co-agonists of the glucagon and glp-1 receptors |
| EP3842449A1 (en) | 2019-12-23 | 2021-06-30 | Merck Sharp & Dohme Corp. | Stapled olefin co-agonists of the glucagon and glp-1 receptors |
| TWI894229B (zh) | 2020-03-16 | 2025-08-21 | 瑞士商諾華公司 | 作為yap/taz-tead蛋白-蛋白相互作用抑制劑之聯芳基衍生物 |
| EP4153584A1 (en) | 2020-05-18 | 2023-03-29 | Merck Sharp & Dohme LLC | Novel diacylglyceride o-acyltransferase 2 inhibitors |
| CR20230160A (es) | 2020-10-08 | 2023-06-02 | Merck Sharp & Dohme Llc | Preparación de derivados de oxindol como nuevos inhibidores de la diacilglicerol o-aciltransferasa 2 |
| MX2024002146A (es) | 2021-08-19 | 2024-03-08 | Merck Sharp & Dohme Llc | Compuestos para el tratamiento de afecciones relacionadas con la actividad de pcsk9. |
| US20230406885A1 (en) | 2022-06-15 | 2023-12-21 | Merck Sharp & Dohme Llc | Cyclic peptides for trapping interleukin-1 beta |
| KR20250107282A (ko) | 2022-12-02 | 2025-07-11 | 머크 샤프 앤드 돔 엘엘씨 | 신규 디아실글리세리드 o-아실트랜스퍼라제 2 억제제로서의 융합된 아졸 유도체의 제조 |
| WO2025060786A1 (zh) * | 2023-09-19 | 2025-03-27 | 湘北威尔曼制药股份有限公司 | 一种六元并五元稠环衍生物及其制备方法和应用 |
| WO2025106386A1 (en) | 2023-11-14 | 2025-05-22 | Merck Sharp & Dohme Llc | A cyclic peptide for trapping interleukin-1 beta |
| WO2025128805A1 (en) | 2023-12-15 | 2025-06-19 | Merck Sharp & Dohme Llc | A cyclic peptide il-1beta trap for the treatment of atherosclerosis and inflammatory disorders |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5686481A (en) * | 1993-12-21 | 1997-11-11 | Smithkline Beecham Corporation | Endothelin receptor antagonists |
| US5482960A (en) * | 1994-11-14 | 1996-01-09 | Warner-Lambert Company | Nonpeptide endothelin antagonists |
| US6297269B1 (en) * | 1995-06-06 | 2001-10-02 | Pfizer Inc. | Substituted n-(indole-2-carbonyl-) amides and derivatives as glycogen phosphorylase inhibitors |
| JP2000516958A (ja) | 1996-08-26 | 2000-12-19 | ジェネティックス・インスチチュート・インコーポレーテッド | ホスホリパーゼ酵素の阻害剤 |
| CA2322162A1 (en) | 1998-02-25 | 1999-09-02 | Genetics Institute, Llc | Inhibitors of phospholipase enzymes |
| EA200000873A1 (ru) | 1998-02-25 | 2001-04-23 | Дженетикс Инститьют, Инк. | Ингибиторы фосфолипазы a |
| EA200000868A1 (ru) | 1998-02-25 | 2001-04-23 | Дженетикс Инститьют, Инк. | Ингибиторы фосфолипаз |
| SK7522001A3 (en) * | 1998-03-31 | 2002-02-05 | Inst For Pharm Discovery Inc | Substituted indolealkanoic acids |
| WO2000028188A1 (en) * | 1998-11-10 | 2000-05-18 | Baker Hughes Incorporated | Self-controlled directional drilling systems and methods |
| HUP0104987A3 (en) | 1998-12-18 | 2002-09-30 | Axys Pharmaceuticals Inc South | Benzimidazole or indole derivatives protease inhibitors, and pharmaceutical compositions containing them |
| WO2001030343A1 (en) * | 1999-10-22 | 2001-05-03 | Merck & Co., Inc. | Pharmaceuticals for treating obesity |
| AU7705601A (en) * | 2000-07-25 | 2002-02-05 | Merck & Co Inc | N-substituted indoles useful in the treatment of diabetes |
| HUP0302477A2 (hu) | 2000-10-10 | 2003-12-29 | Smithkline Beecham Corp. | Szubsztituált indolszármazékok, ezeket tartalmazó gyógyszerkészítmények és ezek alkalmazása PPAR-gamma kötő szerként |
| US6706751B2 (en) * | 2000-12-21 | 2004-03-16 | Hoffman-La Roche Inc. | Dihydroindole and tetrahydroquinoline derivatives |
| JP4292402B2 (ja) | 2001-09-07 | 2009-07-08 | 小野薬品工業株式会社 | インドール誘導体化合物、それらの製造方法およびそれらを有効成分として含有する薬剤 |
| GB0205165D0 (en) * | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
| AU2003214462A1 (en) * | 2002-04-03 | 2003-10-13 | Astrazeneca Ab | Indole derivatives having anti-angiogenetic activity |
| US20040038958A1 (en) | 2002-07-11 | 2004-02-26 | Chris Rundfeldt | Topical treatment of skin diseases |
| CA2495943C (en) * | 2002-08-29 | 2009-07-21 | Merck & Co., Inc. | Indoles having anti-diabetic activity |
| US7129264B2 (en) * | 2003-04-16 | 2006-10-31 | Bristol-Myers Squibb Company | Biarylmethyl indolines and indoles as antithromboembolic agents |
| EP1680131A4 (en) * | 2003-08-01 | 2009-05-27 | Janssen Pharmaceutica Nv | SUBSTITUTED INDOLE-O-GLUCOSIDES |
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2003
- 2003-08-27 CA CA002495943A patent/CA2495943C/en not_active Expired - Fee Related
- 2003-08-27 WO PCT/US2003/026677 patent/WO2004020408A1/en not_active Ceased
- 2003-08-27 BR BR0313825-9A patent/BR0313825A/pt not_active IP Right Cessation
- 2003-08-27 PL PL03375302A patent/PL375302A1/xx not_active Application Discontinuation
- 2003-08-27 US US10/524,697 patent/US7186746B2/en not_active Expired - Lifetime
- 2003-08-27 KR KR1020057003552A patent/KR20050057074A/ko not_active Abandoned
- 2003-08-27 AU AU2003265681A patent/AU2003265681A1/en not_active Abandoned
- 2003-08-27 CN CNB038206919A patent/CN100457730C/zh not_active Expired - Fee Related
- 2003-08-27 PT PT03791952T patent/PT1537078E/pt unknown
- 2003-08-27 JP JP2004531948A patent/JP4377815B2/ja not_active Expired - Fee Related
- 2003-08-27 HR HR20050181A patent/HRP20050181A2/hr not_active Application Discontinuation
- 2003-08-27 ES ES03791952T patent/ES2342596T3/es not_active Expired - Lifetime
- 2003-08-27 MX MXPA05002303A patent/MXPA05002303A/es active IP Right Grant
- 2003-08-27 DE DE60332125T patent/DE60332125D1/de not_active Expired - Lifetime
- 2003-08-27 RU RU2005108668/04A patent/RU2328483C2/ru not_active IP Right Cessation
- 2003-08-27 WO PCT/US2003/027156 patent/WO2004020409A1/en not_active Ceased
- 2003-08-27 NZ NZ538031A patent/NZ538031A/en unknown
- 2003-08-27 DK DK03791952.9T patent/DK1537078T3/da active
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2005
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- 2005-02-08 IL IL16676405A patent/IL166764A0/xx not_active IP Right Cessation
- 2005-02-25 EC EC2005005632A patent/ECSP055632A/es unknown
- 2005-03-16 MA MA28147A patent/MA27396A1/fr unknown
- 2005-03-23 NO NO20051546A patent/NO20051546L/no not_active Application Discontinuation
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2007
- 2007-03-06 US US11/714,341 patent/US7345085B2/en not_active Expired - Lifetime
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| RU2005108668A (ru) | 2005-08-27 |
| DK1537078T3 (da) | 2010-08-02 |
| RU2328483C2 (ru) | 2008-07-10 |
| HRP20050181A2 (en) | 2006-03-31 |
| AU2003265681A1 (en) | 2004-03-19 |
| WO2004020409A1 (en) | 2004-03-11 |
| CN100457730C (zh) | 2009-02-04 |
| ES2342596T3 (es) | 2010-07-09 |
| NZ538031A (en) | 2007-10-26 |
| WO2004020408A1 (en) | 2004-03-11 |
| CA2495943C (en) | 2009-07-21 |
| JP4377815B2 (ja) | 2009-12-02 |
| CA2495943A1 (en) | 2004-03-11 |
| PL375302A1 (en) | 2005-11-28 |
| IL166764A0 (en) | 2006-01-15 |
| US7186746B2 (en) | 2007-03-06 |
| KR20050057074A (ko) | 2005-06-16 |
| HK1083836A1 (zh) | 2006-07-14 |
| CN1678578A (zh) | 2005-10-05 |
| US20070161689A1 (en) | 2007-07-12 |
| BR0313825A (pt) | 2005-07-12 |
| MA27396A1 (fr) | 2005-06-01 |
| NO20051546L (no) | 2005-05-24 |
| JP2006500384A (ja) | 2006-01-05 |
| ECSP055632A (es) | 2005-04-18 |
| US7345085B2 (en) | 2008-03-18 |
| IS7680A (is) | 2005-01-31 |
| MXPA05002303A (es) | 2005-06-08 |
| DE60332125D1 (de) | 2010-05-27 |
| US20050277685A1 (en) | 2005-12-15 |
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