CA2521915A1 - Alpha substituted carboxylic acid as ppar modulators - Google Patents
Alpha substituted carboxylic acid as ppar modulators Download PDFInfo
- Publication number
- CA2521915A1 CA2521915A1 CA002521915A CA2521915A CA2521915A1 CA 2521915 A1 CA2521915 A1 CA 2521915A1 CA 002521915 A CA002521915 A CA 002521915A CA 2521915 A CA2521915 A CA 2521915A CA 2521915 A1 CA2521915 A1 CA 2521915A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- cr11r12
- oxazol
- phenyl
- ethoxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000001732 carboxylic acid derivatives Chemical class 0.000 title description 5
- 101150014691 PPARA gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 339
- 150000003839 salts Chemical class 0.000 claims abstract description 73
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims abstract description 27
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims abstract description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 208000008589 Obesity Diseases 0.000 claims abstract description 10
- 235000020824 obesity Nutrition 0.000 claims abstract description 10
- 238000002360 preparation method Methods 0.000 claims description 188
- 239000000203 mixture Substances 0.000 claims description 148
- 238000000034 method Methods 0.000 claims description 78
- -1 alkali metal cation Chemical class 0.000 claims description 63
- 125000000623 heterocyclic group Chemical group 0.000 claims description 42
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
- 241000124008 Mammalia Species 0.000 claims description 34
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 239000002585 base Substances 0.000 claims description 22
- 125000005843 halogen group Chemical group 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 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 12
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 10
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 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 9
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 239000008103 glucose Substances 0.000 claims description 9
- 235000019260 propionic acid Nutrition 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 8
- 239000003112 inhibitor Substances 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 102000004877 Insulin Human genes 0.000 claims description 6
- 108090001061 Insulin Proteins 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 229940125396 insulin Drugs 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 claims description 5
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 claims description 5
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 claims description 5
- 229940125753 fibrate Drugs 0.000 claims description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 5
- 229940031439 squalene Drugs 0.000 claims description 5
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 claims description 5
- PHJBAEXMMLNDPJ-UHFFFAOYSA-N 1-[3-[3-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]phenoxy]cyclobutane-1-carboxylic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=1)=CC=CC=1C(C=1)=CC=CC=1OC1(C(O)=O)CCC1 PHJBAEXMMLNDPJ-UHFFFAOYSA-N 0.000 claims description 4
- MIJHELLXNOJJSA-UHFFFAOYSA-N 1-[[4-[3-(5-methyl-2-phenyl-1,3-oxazol-4-yl)propoxy]phenyl]methyl]cyclobutane-1-carboxylic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCCOC(C=C1)=CC=C1CC1(C(O)=O)CCC1 MIJHELLXNOJJSA-UHFFFAOYSA-N 0.000 claims description 4
- OYWWKKYTRPWVCD-UHFFFAOYSA-N 2-[[5-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]pyridin-2-yl]methyl]oxolane-2-carboxylic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=N1)=CC=C1CC1(C(O)=O)CCCO1 OYWWKKYTRPWVCD-UHFFFAOYSA-N 0.000 claims description 4
- WXJOPUMLDHSETD-UHFFFAOYSA-N 2-[[6-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]pyridin-3-yl]methyl]oxolane-2-carboxylic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(N=C1)=CC=C1CC1(C(O)=O)CCCO1 WXJOPUMLDHSETD-UHFFFAOYSA-N 0.000 claims description 4
- NFZQKRHNYGYKFG-UHFFFAOYSA-N 2-methyl-2-[3-[[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxycarbonylamino]methyl]phenoxy]propanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(=O)NCC1=CC=CC(OC(C)(C)C(O)=O)=C1 NFZQKRHNYGYKFG-UHFFFAOYSA-N 0.000 claims description 4
- 229940123208 Biguanide Drugs 0.000 claims description 4
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 4
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 4
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 230000015556 catabolic process Effects 0.000 claims description 4
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 4
- 201000008980 hyperinsulinism Diseases 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- CKOGZMNNFXDJPY-UHFFFAOYSA-N 1-[3-[3-[3-(5-methyl-2-phenyl-1,3-oxazol-4-yl)propoxy]phenyl]phenoxy]cyclobutane-1-carboxylic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCCOC(C=1)=CC=CC=1C(C=1)=CC=CC=1OC1(C(O)=O)CCC1 CKOGZMNNFXDJPY-UHFFFAOYSA-N 0.000 claims description 3
- MUWQJZPVPLKJKQ-UHFFFAOYSA-N 1-[3-[3-[[2-(3-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]methoxy]phenyl]phenoxy]cyclobutane-1-carboxylic acid Chemical compound CC=1OC(C=2C=C(F)C=CC=2)=NC=1COC(C=1)=CC=CC=1C(C=1)=CC=CC=1OC1(C(O)=O)CCC1 MUWQJZPVPLKJKQ-UHFFFAOYSA-N 0.000 claims description 3
- UETLLSUOUKKBIY-UHFFFAOYSA-N 1-[3-[3-[[5-(4-methoxyphenyl)-1,2,4-oxadiazol-3-yl]methoxy]phenyl]phenoxy]cyclobutane-1-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1=NC(COC=2C=C(C=CC=2)C=2C=C(OC3(CCC3)C(O)=O)C=CC=2)=NO1 UETLLSUOUKKBIY-UHFFFAOYSA-N 0.000 claims description 3
- OJYQOJVNXIQXFG-UHFFFAOYSA-N 1-[3-[[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxycarbonylamino]methyl]phenoxy]cyclobutane-1-carboxylic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(=O)NCC(C=1)=CC=CC=1OC1(C(O)=O)CCC1 OJYQOJVNXIQXFG-UHFFFAOYSA-N 0.000 claims description 3
- OMOHMQBZICSIHV-UHFFFAOYSA-N 1-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]cyclobutane-1-carboxylic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC1(C(O)=O)CCC1 OMOHMQBZICSIHV-UHFFFAOYSA-N 0.000 claims description 3
- QHAMMGGPQVEHOF-UHFFFAOYSA-N 2-[3-[3-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]phenoxy]butanoic acid Chemical compound CCC(C(O)=O)OC1=CC=CC(C=2C=C(OCCC3=C(OC(=N3)C=3C=CC=CC=3)C)C=CC=2)=C1 QHAMMGGPQVEHOF-UHFFFAOYSA-N 0.000 claims description 3
- VAPQJECFICABMQ-UHFFFAOYSA-N 2-[3-[3-[2-[2-(3-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]phenyl]phenoxy]-2-methylpropanoic acid Chemical compound CC=1OC(C=2C=C(F)C=CC=2)=NC=1CCOC(C=1)=CC=CC=1C1=CC=CC(OC(C)(C)C(O)=O)=C1 VAPQJECFICABMQ-UHFFFAOYSA-N 0.000 claims description 3
- FYAKGDLTNNYZPS-UHFFFAOYSA-N 2-[3-[6-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]pyridin-2-yl]phenoxy]butanoic acid Chemical compound CCC(C(O)=O)OC1=CC=CC(C=2N=C(OCCC3=C(OC(=N3)C=3C=CC=CC=3)C)C=CC=2)=C1 FYAKGDLTNNYZPS-UHFFFAOYSA-N 0.000 claims description 3
- CEULVQJPVVKUGF-UHFFFAOYSA-N 2-[3-[[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxycarbonylamino]methyl]phenoxy]butanoic acid Chemical compound CCC(C(O)=O)OC1=CC=CC(CNC(=O)OCCC2=C(OC(=N2)C=2C=CC=CC=2)C)=C1 CEULVQJPVVKUGF-UHFFFAOYSA-N 0.000 claims description 3
- DZWGILOVKOJRFD-UHFFFAOYSA-N 2-[3-fluoro-4-[[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxycarbonylamino]methyl]phenoxy]-2-methylpropanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(=O)NCC1=CC=C(OC(C)(C)C(O)=O)C=C1F DZWGILOVKOJRFD-UHFFFAOYSA-N 0.000 claims description 3
- MNDAAURXDCSNKA-UHFFFAOYSA-N 2-[[6-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]naphthalen-2-yl]methyl]oxolane-2-carboxylic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1C=C2)=CC=C1C=C2CC1(C(O)=O)CCCO1 MNDAAURXDCSNKA-UHFFFAOYSA-N 0.000 claims description 3
- HEIMHRZFDOAASV-UHFFFAOYSA-N 2-[[6-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]pyridin-3-yl]methyl]oxane-2-carboxylic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(N=C1)=CC=C1CC1(C(O)=O)CCCCO1 HEIMHRZFDOAASV-UHFFFAOYSA-N 0.000 claims description 3
- UKJMTZGBGIXWHJ-UHFFFAOYSA-N 2-[[6-[2-[2-(3-chlorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]pyridin-3-yl]methyl]oxolane-2-carboxylic acid Chemical compound CC=1OC(C=2C=C(Cl)C=CC=2)=NC=1CCOC(N=C1)=CC=C1CC1(C(O)=O)CCCO1 UKJMTZGBGIXWHJ-UHFFFAOYSA-N 0.000 claims description 3
- MNVXKRKUKYAITA-UHFFFAOYSA-N 2-[[6-[2-[2-(3-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]pyridin-3-yl]methyl]oxolane-2-carboxylic acid Chemical compound COC1=CC=CC(C=2OC(C)=C(CCOC=3N=CC(CC4(OCCC4)C(O)=O)=CC=3)N=2)=C1 MNVXKRKUKYAITA-UHFFFAOYSA-N 0.000 claims description 3
- RWXGXHQTECRZHE-UHFFFAOYSA-N 2-ethoxy-3-[3-[3-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]phenyl]propanoic acid Chemical compound CCOC(C(O)=O)CC1=CC=CC(C=2C=C(OCCC3=C(OC(=N3)C=3C=CC=CC=3)C)C=CC=2)=C1 RWXGXHQTECRZHE-UHFFFAOYSA-N 0.000 claims description 3
- XTKDTQMKMYZMHG-UHFFFAOYSA-N 2-ethoxy-3-[3-[[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxycarbonylamino]methyl]phenyl]propanoic acid Chemical compound CCOC(C(O)=O)CC1=CC=CC(CNC(=O)OCCC2=C(OC(=N2)C=2C=CC=CC=2)C)=C1 XTKDTQMKMYZMHG-UHFFFAOYSA-N 0.000 claims description 3
- LRSMHDKOINPHTE-UHFFFAOYSA-N 2-ethoxy-3-[5-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]pyridin-2-yl]propanoic acid Chemical compound C1=NC(CC(OCC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 LRSMHDKOINPHTE-UHFFFAOYSA-N 0.000 claims description 3
- JTZPVQRNTCZQFO-UHFFFAOYSA-N 2-ethoxy-3-[6-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]pyridin-3-yl]propanoic acid Chemical compound N1=CC(CC(OCC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 JTZPVQRNTCZQFO-UHFFFAOYSA-N 0.000 claims description 3
- LERJUFJQHMJLRY-UHFFFAOYSA-N 2-methoxy-2-methyl-3-[6-[3-(5-methyl-2-phenyl-1,3-oxazol-4-yl)propoxy]pyridin-3-yl]propanoic acid Chemical compound N1=CC(CC(C)(OC)C(O)=O)=CC=C1OCCCC1=C(C)OC(C=2C=CC=CC=2)=N1 LERJUFJQHMJLRY-UHFFFAOYSA-N 0.000 claims description 3
- BMMOUOTXLRKEKN-UHFFFAOYSA-N 2-methoxy-3-[6-[2-(4-phenoxyphenyl)ethoxy]pyridin-3-yl]propanoic acid Chemical compound N1=CC(CC(OC)C(O)=O)=CC=C1OCCC(C=C1)=CC=C1OC1=CC=CC=C1 BMMOUOTXLRKEKN-UHFFFAOYSA-N 0.000 claims description 3
- ZAAAPJRNYQMLCO-UHFFFAOYSA-N 2-methoxy-3-[6-[2-[2-(3-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]pyridin-3-yl]-2-methylpropanoic acid Chemical compound COC1=CC=CC(C=2OC(C)=C(CCOC=3N=CC(CC(C)(OC)C(O)=O)=CC=3)N=2)=C1 ZAAAPJRNYQMLCO-UHFFFAOYSA-N 0.000 claims description 3
- PMESMFBQOHJIDA-UHFFFAOYSA-N 2-methoxy-3-[6-[2-[5-methyl-2-(3-methylphenyl)-1,3-oxazol-4-yl]ethoxy]pyridin-3-yl]propanoic acid Chemical compound N1=CC(CC(OC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=C(C)C=CC=2)=N1 PMESMFBQOHJIDA-UHFFFAOYSA-N 0.000 claims description 3
- WUCLCQVTRFQPAF-UHFFFAOYSA-N 2-methyl-2-[3-[3-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl]phenoxy]propanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1COC(C=1)=CC=CC=1C1=CC=CC(OC(C)(C)C(O)=O)=C1 WUCLCQVTRFQPAF-UHFFFAOYSA-N 0.000 claims description 3
- JEQPYDUYXNCNJL-UHFFFAOYSA-N 2-methyl-2-[3-[[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxycarbonylamino]methyl]phenoxy]propanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1COC(=O)NCC1=CC=CC(OC(C)(C)C(O)=O)=C1 JEQPYDUYXNCNJL-UHFFFAOYSA-N 0.000 claims description 3
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- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 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 3
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- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
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- 239000012453 solvate Substances 0.000 claims description 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 11
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 3
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 3
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- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims 3
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Classifications
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
- C07D213/66—One oxygen atom attached in position 3 or 5 having in position 3 an oxygen atom and in each of the positions 4 and 5 a carbon atom bound to an oxygen, sulphur, or nitrogen atom, e.g. pyridoxal
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/14—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by halogen atoms or by nitro or nitroso groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
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- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/08—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C317/22—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
- C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
- C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C62/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C62/30—Unsaturated compounds
- C07C62/34—Unsaturated compounds containing ether groups, groups, groups, or groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
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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
- C07D401/04—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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D405/00—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
- C07D405/02—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
- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyridine Compounds (AREA)
- Furan Compounds (AREA)
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PCT/IB2004/001159 WO2004092145A1 (en) | 2003-04-15 | 2004-04-01 | Alpha substituted carboxylic acid as ppar modulators |
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CA2521915A1 true CA2521915A1 (en) | 2004-10-28 |
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KR (1) | KR20060009846A (es) |
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AP (1) | AP2005003418A0 (es) |
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CL (1) | CL2004000800A1 (es) |
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TN (1) | TNSN05262A1 (es) |
TW (1) | TW200510353A (es) |
UY (1) | UY28266A1 (es) |
WO (1) | WO2004092145A1 (es) |
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CA2567437A1 (en) * | 2004-05-25 | 2005-12-08 | Metabolex, Inc. | Substituted triazoles as modulators of ppar and methods of their preparation |
KR20080019213A (ko) | 2005-05-09 | 2008-03-03 | 아칠리온 파르마세우티칼스 인코포레이티드 | 티아졸 화합물 및 그 사용방법 |
BRPI0622100A2 (pt) | 2006-10-30 | 2011-12-27 | Chroma Therapeutics Ltd | hidroxamatos como inibidores de desacetilase de histona |
US20110021534A1 (en) * | 2007-03-08 | 2011-01-27 | Albireo Ab | 2 -substituted- 3 -phenylpropionic acid derivatives and their use in the treatment of inflammatory bowel disease |
EP2164846A2 (en) | 2007-05-22 | 2010-03-24 | Achillion Pharmaceuticals, Inc. | Heteroaryl substituted thiazoles and their use as antiviral agents. |
US8106209B2 (en) | 2008-06-06 | 2012-01-31 | Achillion Pharmaceuticals, Inc. | Substituted aminothiazole prodrugs of compounds with anti-HCV activity |
US8344018B2 (en) | 2008-07-14 | 2013-01-01 | Gilead Sciences, Inc. | Oxindolyl inhibitor compounds |
WO2010009155A2 (en) | 2008-07-14 | 2010-01-21 | Gilead Colorado, Inc. | Fused heterocyclyc inhibitor compounds |
WO2010009139A2 (en) | 2008-07-14 | 2010-01-21 | Gilead Colorado, Inc. | Imidazolyl pyrimidine inhibitor compounds |
MX2011001090A (es) | 2008-07-28 | 2011-03-15 | Gilead Sciences Inc | Compuestos de inhibidor de desacetilasa de histona de cicloalquilideno y heterocicloalquilideno. |
BRPI1010883A2 (pt) | 2009-06-08 | 2018-07-10 | Gilead Sciences Inc | compostos inibidores da anilina cicloalquilcarbamato benzamida hdac. |
CN102459159A (zh) | 2009-06-08 | 2012-05-16 | 吉利德科学股份有限公司 | 烷酰基氨基苯甲酰胺苯胺hdac抑制剂化合物 |
DE102010055499A1 (de) * | 2010-12-22 | 2011-06-16 | W.C. Heraeus Gmbh | Prozess zur Herstellung von Bendamustinalkylester, Bendarmustin sowie Derivaten davon |
CA2853439A1 (en) | 2011-10-31 | 2013-05-10 | Xenon Pharmaceuticals Inc. | Benzenesulfonamide compounds and their use as therapeutic agents |
US9481677B2 (en) | 2011-10-31 | 2016-11-01 | Xenon Pharmaceuticals Inc. | Biaryl ether sulfonamides and their use as therapeutic agents |
FR2982858B1 (fr) * | 2011-11-18 | 2013-11-29 | Rhodia Operations | Procede de fabrication de composes comprenant des fonctions nitriles |
FR2984322B1 (fr) * | 2011-12-16 | 2013-12-20 | Rhodia Operations | Procede de fabrication de composes comprenant des fonctions nitriles |
SG11201408284VA (en) | 2012-05-22 | 2015-02-27 | Xenon Pharmaceuticals Inc | N-substituted benzamides and their use in the treatment of pain |
WO2014008458A2 (en) | 2012-07-06 | 2014-01-09 | Genentech, Inc. | N-substituted benzamides and methods of use thereof |
US9550775B2 (en) | 2013-03-14 | 2017-01-24 | Genentech, Inc. | Substituted triazolopyridines and methods of use thereof |
BR112015023397A2 (pt) | 2013-03-15 | 2017-07-18 | Genentech Inc | benzoxazois substituídos e métodos de uso dos mesmos |
MX2016006936A (es) | 2013-11-27 | 2016-10-05 | Genentech Inc | Benzamidas sustituidas y metodos para usarlas. |
CN106715418A (zh) | 2014-07-07 | 2017-05-24 | 基因泰克公司 | 治疗化合物及其使用方法 |
BR112017024853A2 (pt) | 2015-05-22 | 2018-08-07 | Genentech Inc | composto, composição farmacêutica, método para tratar uma doença ou condição em um mamífero, para tratamento de prurido em um mamífero, para tratamento ou profilaxia e uso de um composto |
JP2018526371A (ja) | 2015-08-27 | 2018-09-13 | ジェネンテック, インコーポレイテッド | 治療化合物及びその使用方法 |
SG10202007787RA (en) | 2015-09-28 | 2020-09-29 | Genentech Inc | Therapeutic compounds and methods of use thereof |
EP3380466A1 (en) | 2015-11-25 | 2018-10-03 | Genentech, Inc. | Substituted benzamides useful as sodium channel blockers |
JP2019513714A (ja) | 2016-03-30 | 2019-05-30 | ジェネンテック, インコーポレイテッド | 置換ベンズアミド及びその使用方法 |
AU2017347549A1 (en) | 2016-10-17 | 2019-05-02 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
CN110546148A (zh) | 2017-03-24 | 2019-12-06 | 基因泰克公司 | 作为钠通道抑制剂的4-哌啶-n-(嘧啶-4-基)色满-7-磺酰胺衍生物 |
TW202000651A (zh) | 2018-02-26 | 2020-01-01 | 美商建南德克公司 | 治療性組成物及其使用方法 |
US10947251B2 (en) | 2018-03-30 | 2021-03-16 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
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PT1088824E (pt) * | 1999-09-30 | 2004-04-30 | Pfizer Prod Inc | Pirrolil-amidas biciclicas como inibidores de glicogenio-fosforilase |
CA2438492A1 (en) * | 2001-02-15 | 2002-08-22 | Pfizer Products Inc. | Proliferative activator receptor (ppar) compounds |
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AP2005003418A0 (en) | 2005-12-31 |
UY28266A1 (es) | 2004-11-30 |
ECSP056105A (es) | 2006-03-01 |
NO20055370D0 (no) | 2005-11-14 |
NL1025946A1 (nl) | 2004-10-18 |
EA200501462A1 (ru) | 2006-04-28 |
EP1615899A1 (en) | 2006-01-18 |
MXPA05010967A (es) | 2005-11-28 |
CN1805943A (zh) | 2006-07-19 |
PE20050415A1 (es) | 2005-06-13 |
KR20060009846A (ko) | 2006-02-01 |
AU2004230316A1 (en) | 2004-10-28 |
CL2004000800A1 (es) | 2005-03-04 |
JP2006523671A (ja) | 2006-10-19 |
OA13157A (en) | 2006-12-13 |
TW200510353A (en) | 2005-03-16 |
AR044514A1 (es) | 2005-09-14 |
NL1025946C2 (nl) | 2005-02-01 |
MA27764A1 (fr) | 2006-02-01 |
BRPI0409429A (pt) | 2006-04-18 |
TNSN05262A1 (fr) | 2007-07-10 |
NO20055370L (no) | 2006-01-12 |
IS8033A (is) | 2005-09-15 |
ZA200508362B (en) | 2006-11-29 |
PA8600201A1 (es) | 2005-02-04 |
WO2004092145A1 (en) | 2004-10-28 |
WO2004092145A8 (en) | 2005-05-12 |
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