WO2004063155A1 - Fused heterocyclic derivatives as ppar modulators - Google Patents
Fused heterocyclic derivatives as ppar modulators Download PDFInfo
- Publication number
- WO2004063155A1 WO2004063155A1 PCT/US2003/039120 US0339120W WO2004063155A1 WO 2004063155 A1 WO2004063155 A1 WO 2004063155A1 US 0339120 W US0339120 W US 0339120W WO 2004063155 A1 WO2004063155 A1 WO 2004063155A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- alkyl
- phenyl
- group
- aryl
- methyl
- Prior art date
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- 101150014691 PPARA gene Proteins 0.000 title 1
- 125000000623 heterocyclic group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 234
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 119
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 49
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 43
- 229940124530 sulfonamide Drugs 0.000 claims abstract description 17
- 150000003456 sulfonamides Chemical class 0.000 claims abstract description 17
- 150000003536 tetrazoles Chemical class 0.000 claims abstract description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 140
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 132
- 229910052739 hydrogen Inorganic materials 0.000 claims description 124
- 239000001257 hydrogen Substances 0.000 claims description 115
- 150000002431 hydrogen Chemical class 0.000 claims description 61
- 125000001424 substituent group Chemical group 0.000 claims description 53
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 claims description 51
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 50
- 125000003118 aryl group Chemical group 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 48
- 125000003545 alkoxy group Chemical group 0.000 claims description 47
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 46
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 44
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 40
- 125000001188 haloalkyl group Chemical group 0.000 claims description 38
- 125000004104 aryloxy group Chemical group 0.000 claims description 35
- -1 aryl- Co-4-alkyl Chemical group 0.000 claims description 33
- 125000001072 heteroaryl group Chemical group 0.000 claims description 28
- 125000005466 alkylenyl group Chemical group 0.000 claims description 26
- 150000003839 salts Chemical class 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 24
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 22
- 239000004480 active ingredient Substances 0.000 claims description 22
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 21
- 241000124008 Mammalia Species 0.000 claims description 20
- 229920006395 saturated elastomer Polymers 0.000 claims description 20
- 125000003342 alkenyl group Chemical group 0.000 claims description 19
- 125000002619 bicyclic group Chemical group 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 18
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 17
- 125000004043 oxo group Chemical group O=* 0.000 claims description 17
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims description 16
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 239000012453 solvate Substances 0.000 claims description 12
- 125000002837 carbocyclic group Chemical group 0.000 claims description 11
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 11
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 206010012601 diabetes mellitus Diseases 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 150000004677 hydrates Chemical class 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 8
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 8
- 108010015181 PPAR delta Proteins 0.000 claims description 8
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 8
- 150000001721 carbon Chemical group 0.000 claims description 8
- 125000005605 benzo group Chemical group 0.000 claims description 7
- 150000003857 carboxamides Chemical class 0.000 claims description 7
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 5
- 102000048124 delta Opioid Receptors Human genes 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- QXMPETNONJQAMV-UHFFFAOYSA-N 2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SCC=2C=3N=C(SC=3C=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 QXMPETNONJQAMV-UHFFFAOYSA-N 0.000 claims description 4
- MLRJYOJSBPJMGJ-UHFFFAOYSA-N 2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SCC2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 MLRJYOJSBPJMGJ-UHFFFAOYSA-N 0.000 claims description 4
- UMWZZLDNVUQPRY-UHFFFAOYSA-N 3-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SCC=2C=3N=C(SC=3C=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 UMWZZLDNVUQPRY-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- NKTJHYBYKQVDLG-UHFFFAOYSA-N 2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-4,5,6,7,8,9-hexahydrocycloocta[d][1,3]thiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SCC2C=3N=C(SC=3CCCCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 NKTJHYBYKQVDLG-UHFFFAOYSA-N 0.000 claims description 3
- ISFGGMBEAJESIE-UHFFFAOYSA-N 2-[3-[[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-4-yl]methoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OCC=2C=3N=C(SC=3C=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 ISFGGMBEAJESIE-UHFFFAOYSA-N 0.000 claims description 3
- AJPCZXSCOFDKMF-UHFFFAOYSA-N 2-[3-[[2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OCC2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 AJPCZXSCOFDKMF-UHFFFAOYSA-N 0.000 claims description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 229960003424 phenylacetic acid Drugs 0.000 claims description 3
- 239000003279 phenylacetic acid Substances 0.000 claims description 3
- 102000005962 receptors Human genes 0.000 claims description 3
- 108020003175 receptors Proteins 0.000 claims description 3
- LSYQBJIIKXNEHU-UHFFFAOYSA-N 2-[2-ethyl-4-[[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-7-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(CC)=CC(SCC=2C=3SC(=NC=3C=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 LSYQBJIIKXNEHU-UHFFFAOYSA-N 0.000 claims description 2
- WPGUAIZCNYEENQ-INIZCTEOSA-N 2-[2-methyl-4-[[(4r)-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SC[C@H]2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 WPGUAIZCNYEENQ-INIZCTEOSA-N 0.000 claims description 2
- MLRJYOJSBPJMGJ-HNNXBMFYSA-N 2-[2-methyl-4-[[(4r)-2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SC[C@H]2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 MLRJYOJSBPJMGJ-HNNXBMFYSA-N 0.000 claims description 2
- WPGUAIZCNYEENQ-MRXNPFEDSA-N 2-[2-methyl-4-[[(4s)-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SC[C@@H]2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 WPGUAIZCNYEENQ-MRXNPFEDSA-N 0.000 claims description 2
- XSEIFFMZKVPKCQ-QGZVFWFLSA-N 2-[2-methyl-4-[[(4s)-2-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-4h-cyclohepta[d][1,3]thiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SC[C@@H]2C=3N=C(SC=3CCCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 XSEIFFMZKVPKCQ-QGZVFWFLSA-N 0.000 claims description 2
- MLRJYOJSBPJMGJ-OAHLLOKOSA-N 2-[2-methyl-4-[[(4s)-2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SC[C@@H]2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 MLRJYOJSBPJMGJ-OAHLLOKOSA-N 0.000 claims description 2
- MOMMQBFMXWNUCB-UHFFFAOYSA-N 2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methoxy]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(OCC2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 MOMMQBFMXWNUCB-UHFFFAOYSA-N 0.000 claims description 2
- WPGUAIZCNYEENQ-UHFFFAOYSA-N 2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SCC2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 WPGUAIZCNYEENQ-UHFFFAOYSA-N 0.000 claims description 2
- XSEIFFMZKVPKCQ-UHFFFAOYSA-N 2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-4h-cyclohepta[d][1,3]thiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SCC2C=3N=C(SC=3CCCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 XSEIFFMZKVPKCQ-UHFFFAOYSA-N 0.000 claims description 2
- MQFZYVYYQVKLOX-UHFFFAOYSA-N 2-[2-methyl-4-[[7-methyl-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=2N=C(C=3C=CC(=CC=3)C(F)(F)F)SC=2C(C)CCC1CSC1=CC=C(OCC(O)=O)C(C)=C1 MQFZYVYYQVKLOX-UHFFFAOYSA-N 0.000 claims description 2
- AYEMAHRIKLHTPJ-INIZCTEOSA-N 2-[3-[[(4r)-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OC[C@H]2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 AYEMAHRIKLHTPJ-INIZCTEOSA-N 0.000 claims description 2
- AJPCZXSCOFDKMF-HNNXBMFYSA-N 2-[3-[[(4r)-2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OC[C@H]2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 AJPCZXSCOFDKMF-HNNXBMFYSA-N 0.000 claims description 2
- AYEMAHRIKLHTPJ-MRXNPFEDSA-N 2-[3-[[(4s)-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OC[C@@H]2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 AYEMAHRIKLHTPJ-MRXNPFEDSA-N 0.000 claims description 2
- AJPCZXSCOFDKMF-OAHLLOKOSA-N 2-[3-[[(4s)-2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OC[C@@H]2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 AJPCZXSCOFDKMF-OAHLLOKOSA-N 0.000 claims description 2
- VRZRNMUGRLBYMH-UHFFFAOYSA-N 2-[3-[[2-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-4h-cyclohepta[d][1,3]thiazol-4-yl]methoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OCC2C=3N=C(SC=3CCCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 VRZRNMUGRLBYMH-UHFFFAOYSA-N 0.000 claims description 2
- WNGDCAVZHBQGEU-UHFFFAOYSA-N 2-methyl-2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-4-yl]methoxy]phenoxy]propanoic acid Chemical compound C1=C(OC(C)(C)C(O)=O)C(C)=CC(OCC=2C=3N=C(SC=3C=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 WNGDCAVZHBQGEU-UHFFFAOYSA-N 0.000 claims description 2
- GEWKLPAJUKPLJR-SFHVURJKSA-N 3-[2-methyl-4-[[(4r)-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methoxy]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(OC[C@H]2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 GEWKLPAJUKPLJR-SFHVURJKSA-N 0.000 claims description 2
- VSMDKBVLWCUDSE-SFHVURJKSA-N 3-[2-methyl-4-[[(4r)-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SC[C@H]2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 VSMDKBVLWCUDSE-SFHVURJKSA-N 0.000 claims description 2
- MASRIAZPJQZFBO-KRWDZBQOSA-N 3-[2-methyl-4-[[(4r)-2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SC[C@H]2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 MASRIAZPJQZFBO-KRWDZBQOSA-N 0.000 claims description 2
- GEWKLPAJUKPLJR-GOSISDBHSA-N 3-[2-methyl-4-[[(4s)-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methoxy]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(OC[C@@H]2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 GEWKLPAJUKPLJR-GOSISDBHSA-N 0.000 claims description 2
- VSMDKBVLWCUDSE-GOSISDBHSA-N 3-[2-methyl-4-[[(4s)-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SC[C@@H]2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 VSMDKBVLWCUDSE-GOSISDBHSA-N 0.000 claims description 2
- AFPSGVLCIZLFNL-LJQANCHMSA-N 3-[2-methyl-4-[[(4s)-2-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-4h-cyclohepta[d][1,3]thiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SC[C@@H]2C=3N=C(SC=3CCCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 AFPSGVLCIZLFNL-LJQANCHMSA-N 0.000 claims description 2
- MASRIAZPJQZFBO-QGZVFWFLSA-N 3-[2-methyl-4-[[(4s)-2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SC[C@@H]2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 MASRIAZPJQZFBO-QGZVFWFLSA-N 0.000 claims description 2
- PXVZUEYBHCULQB-UHFFFAOYSA-N 3-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-4-yl]methoxy]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(OCC=2C=3N=C(SC=3C=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 PXVZUEYBHCULQB-UHFFFAOYSA-N 0.000 claims description 2
- VSMDKBVLWCUDSE-UHFFFAOYSA-N 3-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SCC2C=3N=C(SC=3CCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 VSMDKBVLWCUDSE-UHFFFAOYSA-N 0.000 claims description 2
- RJTQUAYEWRMUMM-UHFFFAOYSA-N 3-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methoxy]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(OCC2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 RJTQUAYEWRMUMM-UHFFFAOYSA-N 0.000 claims description 2
- MASRIAZPJQZFBO-UHFFFAOYSA-N 3-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4h-cyclopenta[d][1,3]thiazol-4-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=CC(SCC2C=3N=C(SC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 MASRIAZPJQZFBO-UHFFFAOYSA-N 0.000 claims description 2
- 108020005497 Nuclear hormone receptor Proteins 0.000 claims description 2
- PKCBADCPSHELDO-UHFFFAOYSA-N ethyl 2-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-4-yl]methylsulfanyl]phenoxy]acetate Chemical compound C1=C(C)C(OCC(=O)OCC)=CC=C1SCC1=CC=CC2=C1N=C(C=1C=CC(=CC=1)C(F)(F)F)S2 PKCBADCPSHELDO-UHFFFAOYSA-N 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 21
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 3
- LKTNJCONYPMERP-FQEVSTJZSA-N (2s)-2-methoxy-3-[4-[[2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazol-4-yl]methoxy]phenyl]propanoic acid Chemical compound C1=CC(C[C@H](OC)C(O)=O)=CC=C1OCC1=CC=CC2=C1N=C(C=1C=CC(=CC=1)C(F)(F)F)S2 LKTNJCONYPMERP-FQEVSTJZSA-N 0.000 claims 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
- XSEIFFMZKVPKCQ-KRWDZBQOSA-N 2-[2-methyl-4-[[(4r)-2-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-4h-cyclohepta[d][1,3]thiazol-4-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C)=CC(SC[C@H]2C=3N=C(SC=3CCCC2)C=2C=CC(=CC=2)C(F)(F)F)=C1 XSEIFFMZKVPKCQ-KRWDZBQOSA-N 0.000 claims 1
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- BSVIOYCZTJRBDB-UHFFFAOYSA-N methyl 2-(3-methoxyphenyl)acetate Chemical compound COC(=O)CC1=CC=CC(OC)=C1 BSVIOYCZTJRBDB-UHFFFAOYSA-N 0.000 description 1
- ZBQBSRXDNRKDPZ-UHFFFAOYSA-N methyl 2-(4-hydroxy-2-methylphenyl)acetate Chemical compound COC(=O)CC1=CC=C(O)C=C1C ZBQBSRXDNRKDPZ-UHFFFAOYSA-N 0.000 description 1
- XXTWNWQHEGVDMQ-UHFFFAOYSA-N methyl 2-(4-methoxy-2-methylphenyl)acetate Chemical compound COC(=O)CC1=CC=C(OC)C=C1C XXTWNWQHEGVDMQ-UHFFFAOYSA-N 0.000 description 1
- BRYPZFFZTRQJSU-UHFFFAOYSA-N methyl 2-(6-hydroxy-1-benzofuran-3-yl)acetate Chemical compound OC1=CC=C2C(CC(=O)OC)=COC2=C1 BRYPZFFZTRQJSU-UHFFFAOYSA-N 0.000 description 1
- HIZAWDWPLNYOKB-UHFFFAOYSA-N methyl 2-(6-hydroxy-1-benzofuran-3-yl)propanoate Chemical compound OC1=CC=C2C(C(C)C(=O)OC)=COC2=C1 HIZAWDWPLNYOKB-UHFFFAOYSA-N 0.000 description 1
- NTNUDYROPUKXNA-UHFFFAOYSA-N methyl 2-(triphenyl-$l^{5}-phosphanylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC)C1=CC=CC=C1 NTNUDYROPUKXNA-UHFFFAOYSA-N 0.000 description 1
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- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
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- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D263/57—Aryl or substituted aryl radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
- C07D277/66—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2 with aromatic rings or ring systems directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D417/02—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 two hetero rings
- C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
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CA002509202A CA2509202A1 (en) | 2003-01-06 | 2003-12-31 | Fused heterocyclic derivatives as ppar modulators |
AU2003296405A AU2003296405A1 (en) | 2003-01-06 | 2003-12-31 | Fused heterocyclic derivatives as ppar modulators |
JP2004566526A JP2006516254A (en) | 2003-01-06 | 2003-12-31 | Fused heterocyclic derivatives as PPAR modulators |
US10/539,477 US7384965B2 (en) | 2003-01-06 | 2003-12-31 | Fused heterocyclic derivatives as PPAR modulators |
EP03815196A EP1585726A1 (en) | 2003-01-06 | 2003-12-31 | Fused heterocyclic derivatives as ppar modulators |
US12/099,929 US7598266B2 (en) | 2003-01-06 | 2008-04-09 | Fused heterocyclic derivatives as PPAR modulators |
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US43854003P | 2003-01-06 | 2003-01-06 | |
US43854103P | 2003-01-06 | 2003-01-06 | |
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US60/438,541 | 2003-01-06 |
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US12/099,929 Division US7598266B2 (en) | 2003-01-06 | 2008-04-09 | Fused heterocyclic derivatives as PPAR modulators |
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WO2004063155A1 true WO2004063155A1 (en) | 2004-07-29 |
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PCT/US2003/039120 WO2004063155A1 (en) | 2003-01-06 | 2003-12-31 | Fused heterocyclic derivatives as ppar modulators |
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US (2) | US7384965B2 (en) |
EP (1) | EP1585726A1 (en) |
JP (1) | JP2006516254A (en) |
AU (1) | AU2003296405A1 (en) |
CA (1) | CA2509202A1 (en) |
WO (1) | WO2004063155A1 (en) |
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JP2009507846A (en) * | 2005-09-07 | 2009-02-26 | プレキシコン,インコーポレーテッド | PPAR active compounds |
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AU2003296405A1 (en) | 2004-08-10 |
US20060205744A1 (en) | 2006-09-14 |
US7598266B2 (en) | 2009-10-06 |
EP1585726A1 (en) | 2005-10-19 |
JP2006516254A (en) | 2006-06-29 |
CA2509202A1 (en) | 2004-07-29 |
US20090054479A1 (en) | 2009-02-26 |
US7384965B2 (en) | 2008-06-10 |
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