JP2006525329A - 置換カルボン酸類 - Google Patents

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Publication number

JP2006525329A

JP2006525329A JP2006509981A JP2006509981A JP2006525329A JP 2006525329 A JP2006525329 A JP 2006525329A JP 2006509981 A JP2006509981 A JP 2006509981A JP 2006509981 A JP2006509981 A JP 2006509981A JP 2006525329 A JP2006525329 A JP 2006525329A

Authority

JP

Japan

Prior art keywords

alkyl

phenyl

biphenyl

benzyl

benzofuran

Prior art date

2003-04-30

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.)

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• 150000001735 carboxylic acids Chemical class 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 372
• 238000000034 method Methods 0.000 claims abstract description 82
• 238000011282 treatment Methods 0.000 claims abstract description 34
• 150000003839 salts Chemical class 0.000 claims abstract description 22
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
• 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 15
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 171
• 229910052736 halogen Inorganic materials 0.000 claims description 162
• 150000002367 halogens Chemical class 0.000 claims description 162
• -1 R 21 Chemical compound 0.000 claims description 130
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 105
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 61
• 125000005037 alkyl phenyl group Chemical group 0.000 claims description 56
• 125000000217 alkyl group Chemical group 0.000 claims description 52
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 45
• 229910052739 hydrogen Inorganic materials 0.000 claims description 44
• 125000001188 haloalkyl group Chemical group 0.000 claims description 41
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 39
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 37
• 125000003118 aryl group Chemical group 0.000 claims description 27
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 27
• 125000001041 indolyl group Chemical group 0.000 claims description 27
• 229910052799 carbon Inorganic materials 0.000 claims description 26
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 24
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims description 24
• 125000003545 alkoxy group Chemical group 0.000 claims description 23
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 23
• 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 22
• 125000004122 cyclic group Chemical group 0.000 claims description 20
• 125000002252 acyl group Chemical group 0.000 claims description 18
• 125000003386 piperidinyl group Chemical group 0.000 claims description 18
• TXCDCPKCNAJMEE-UHFFFAOYSA-N dibenzofuran Chemical compound C1=CC=C2C3=CC=CC=C3OC2=C1 TXCDCPKCNAJMEE-UHFFFAOYSA-N 0.000 claims description 17
• 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims description 17
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 17
• 125000005545 phthalimidyl group Chemical group 0.000 claims description 16
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
• 125000002757 morpholinyl group Chemical group 0.000 claims description 14
• 125000001072 heteroaryl group Chemical group 0.000 claims description 13
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 13
• 125000004076 pyridyl group Chemical group 0.000 claims description 13
• 239000002904 solvent Substances 0.000 claims description 13
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 12
• 125000004988 dibenzothienyl group Chemical group C1(=CC=CC=2SC3=C(C21)C=CC=C3)* 0.000 claims description 12
• 125000001624 naphthyl group Chemical group 0.000 claims description 10
• 125000001424 substituent group Chemical group 0.000 claims description 10
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 9
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 9
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
• 125000001544 thienyl group Chemical group 0.000 claims description 9
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 8
• 125000005605 benzo group Chemical group 0.000 claims description 7
• 239000000126 substance Substances 0.000 claims description 7
• 239000002671 adjuvant Substances 0.000 claims description 6
• FOUKSPNWVQXNSE-UHFFFAOYSA-N 4-[4-(4-dibenzofuran-4-ylphenyl)phenyl]-4-oxo-2-[[3-(trifluoromethyl)phenyl]methyl]butanoic acid Chemical compound C=1C=C(C=2C=CC(=CC=2)C=2C3=C(C4=CC=CC=C4O3)C=CC=2)C=CC=1C(=O)CC(C(=O)O)CC1=CC=CC(C(F)(F)F)=C1 FOUKSPNWVQXNSE-UHFFFAOYSA-N 0.000 claims description 5
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 5
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims description 5
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 5
• NQDPPXMOGTWHAA-UHFFFAOYSA-N 2-benzyl-4-[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]phenyl]-4-oxobutanoic acid Chemical compound C=1C=CC=CC=1CC(C(=O)O)CC(=O)C(C=C1)=CC=C1C(C=C1)=CC=C1C(C1=CC=CC=C1O1)=C1CC1=CC=CC=C1 NQDPPXMOGTWHAA-UHFFFAOYSA-N 0.000 claims description 4
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 4
• 235000004279 alanine Nutrition 0.000 claims description 4
• 125000002541 furyl group Chemical group 0.000 claims description 4
• 229960005190 phenylalanine Drugs 0.000 claims description 4
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
• BCAPAVNRPJLWBU-UHFFFAOYSA-N 2-[[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]phenyl]sulfonylamino]butanoic acid Chemical compound C1=CC(S(=O)(=O)NC(CC)C(O)=O)=CC=C1C1=CC=C(C=2C3=CC=CC=C3OC=2CC=2C=CC=CC=2)C=C1 BCAPAVNRPJLWBU-UHFFFAOYSA-N 0.000 claims description 3
• WAKZELVPMHJKIX-UHFFFAOYSA-N 2-benzyl-4-[2-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]phenyl]-4-oxobutanoic acid Chemical compound C=1C=CC=CC=1CC(C(=O)O)CC(=O)C1=CC=CC=C1C(C=C1)=CC=C1C(C1=CC=CC=C1O1)=C1CC1=CC=CC=C1 WAKZELVPMHJKIX-UHFFFAOYSA-N 0.000 claims description 3
• VCOJXFLHAWTRFN-UHFFFAOYSA-N 2-benzyl-4-[3-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]phenyl]-4-oxobutanoic acid Chemical compound C=1C=CC=CC=1CC(C(=O)O)CC(=O)C(C=1)=CC=CC=1C(C=C1)=CC=C1C(C1=CC=CC=C1O1)=C1CC1=CC=CC=C1 VCOJXFLHAWTRFN-UHFFFAOYSA-N 0.000 claims description 3
• MPXRREHOMCUVNZ-UHFFFAOYSA-N 2-benzyl-4-[4-(4-indol-1-ylphenyl)phenyl]-4-oxobutanoic acid Chemical compound C=1C=C(C=2C=CC(=CC=2)N2C3=CC=CC=C3C=C2)C=CC=1C(=O)CC(C(=O)O)CC1=CC=CC=C1 MPXRREHOMCUVNZ-UHFFFAOYSA-N 0.000 claims description 3
• WLXCNKISKIXXST-UHFFFAOYSA-N 2-benzyl-4-[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]-2,6-dimethylphenyl]-4-oxobutanoic acid Chemical compound CC1=CC(C=2C=CC(=CC=2)C=2C3=CC=CC=C3OC=2CC=2C=CC=CC=2)=CC(C)=C1C(=O)CC(C(O)=O)CC1=CC=CC=C1 WLXCNKISKIXXST-UHFFFAOYSA-N 0.000 claims description 3
• JZUWBNLKHMQGNS-UHFFFAOYSA-N 4-[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]phenyl]-2-[(4-methylsulfonylphenyl)methyl]-4-oxobutanoic acid Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CC(C(O)=O)CC(=O)C1=CC=C(C=2C=CC(=CC=2)C=2C3=CC=CC=C3OC=2CC=2C=CC=CC=2)C=C1 JZUWBNLKHMQGNS-UHFFFAOYSA-N 0.000 claims description 3
• QNYLAIBEHNOPPA-UHFFFAOYSA-N 4-[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]phenyl]-2-[2-(1,3-dioxoisoindol-2-yl)ethyl]-4-oxobutanoic acid Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCC(C(=O)O)CC(=O)C(C=C1)=CC=C1C(C=C1)=CC=C1C(C1=CC=CC=C1O1)=C1CC1=CC=CC=C1 QNYLAIBEHNOPPA-UHFFFAOYSA-N 0.000 claims description 3
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 3
• GSJVCQGPHKZZTL-JGCGQSQUSA-N (2R)-2,5-diamino-2-[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]-2-nitrophenyl]-5-oxopentanoic acid Chemical compound C(C1=CC=CC=C1)C=1OC2=C(C=1C1=CC=C(C=C1)C1=CC(=C(C=C1)[C@](N)(CCC(N)=O)C(=O)O)[N+](=O)[O-])C=CC=C2 GSJVCQGPHKZZTL-JGCGQSQUSA-N 0.000 claims description 2
• RVJUPLWFUPACJL-JGCGQSQUSA-N (2r)-2-[4-[4-(1-butylindolizin-2-yl)phenyl]phenoxy]-3-phenylpropanoic acid Chemical compound C([C@@H](OC1=CC=C(C=C1)C1=CC=C(C=C1)C=1C(=C2C=CC=CN2C=1)CCCC)C(O)=O)C1=CC=CC=C1 RVJUPLWFUPACJL-JGCGQSQUSA-N 0.000 claims description 2
• ALOFTPNNFBMPOW-MGBGTMOVSA-N (2r)-2-[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]-n-methyl-2-nitroanilino]-3-phenylpropanoic acid Chemical compound C([C@@H](N(C)C=1C(=CC(=CC=1)C=1C=CC(=CC=1)C=1C2=CC=CC=C2OC=1CC=1C=CC=CC=1)[N+]([O-])=O)C(O)=O)C1=CC=CC=C1 ALOFTPNNFBMPOW-MGBGTMOVSA-N 0.000 claims description 2
• QXMNORFCWALUQG-XIFFEERXSA-N (2s)-2-[4-[4-(1-butylindolizin-2-yl)phenyl]phenoxy]-4-phenylbutanoic acid Chemical compound C([C@H](OC1=CC=C(C=C1)C1=CC=C(C=C1)C=1C(=C2C=CC=CN2C=1)CCCC)C(O)=O)CC1=CC=CC=C1 QXMNORFCWALUQG-XIFFEERXSA-N 0.000 claims description 2
• LBHTUNQLUBVJPB-KDXMTYKHSA-N (2s)-2-[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]-2-[(2-phenylacetyl)amino]anilino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC=1C(=CC(=CC=1)C=1C=CC(=CC=1)C=1C2=CC=CC=C2OC=1CC=1C=CC=CC=1)NC(=O)CC=1C=CC=CC=1)C1=CC=CC=C1 LBHTUNQLUBVJPB-KDXMTYKHSA-N 0.000 claims description 2
• TVGXOXUAFKXOQE-VWLOTQADSA-N (2s)-2-[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]-2-nitroanilino]-3-hydroxypropanoic acid Chemical compound C1=C([N+]([O-])=O)C(N[C@@H](CO)C(O)=O)=CC=C1C1=CC=C(C=2C3=CC=CC=C3OC=2CC=2C=CC=CC=2)C=C1 TVGXOXUAFKXOQE-VWLOTQADSA-N 0.000 claims description 2
• VZQPGBMZSRZGNS-HKBQPEDESA-N (2s)-2-[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]-2-nitroanilino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC=1C(=CC(=CC=1)C=1C=CC(=CC=1)C=1C2=CC=CC=C2OC=1CC=1C=CC=CC=1)[N+]([O-])=O)C1=CC=CC=C1 VZQPGBMZSRZGNS-HKBQPEDESA-N 0.000 claims description 2
• PLDAFOFKTYIKNJ-MHZLTWQESA-N (2s)-2-[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]-2-nitroanilino]-4-methylsulfanylbutanoic acid Chemical compound C1=C([N+]([O-])=O)C(N[C@@H](CCSC)C(O)=O)=CC=C1C1=CC=C(C=2C3=CC=CC=C3OC=2CC=2C=CC=CC=2)C=C1 PLDAFOFKTYIKNJ-MHZLTWQESA-N 0.000 claims description 2
• CTHQHLFBRGKYCW-PMERELPUSA-N (2s)-2-[4-[4-(2-benzyl-4-fluoro-1-benzofuran-3-yl)phenyl]-2-nitroanilino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC=1C(=CC(=CC=1)C=1C=CC(=CC=1)C=1C2=C(F)C=CC=C2OC=1CC=1C=CC=CC=1)[N+]([O-])=O)C1=CC=CC=C1 CTHQHLFBRGKYCW-PMERELPUSA-N 0.000 claims description 2
• JIZSLXVSDDGOQR-DHUJRADRSA-N (2s)-2-[4-[4-[(2-benzyl-7-ethoxy-1-benzofuran-4-yl)methyl]phenyl]-2-nitroanilino]-3-phenylpropanoic acid Chemical compound C([C@H](NC1=CC=C(C=C1[N+]([O-])=O)C1=CC=C(C=C1)CC1=CC=C(C=2OC(CC=3C=CC=CC=3)=CC=21)OCC)C(O)=O)C1=CC=CC=C1 JIZSLXVSDDGOQR-DHUJRADRSA-N 0.000 claims description 2
• SKVKSLAIKOIQDV-HKBQPEDESA-N (2s)-2-[[4-[4-(1-butylindolizin-2-yl)phenyl]benzoyl]amino]-3-phenylpropanoic acid Chemical compound C([C@H](NC(=O)C1=CC=C(C=C1)C1=CC=C(C=C1)C=1C(=C2C=CC=CN2C=1)CCCC)C(O)=O)C1=CC=CC=C1 SKVKSLAIKOIQDV-HKBQPEDESA-N 0.000 claims description 2
• YAMKTWOCIRVYGC-HKBQPEDESA-N (2s)-2-[[4-[4-(1-butylindolizin-2-yl)phenyl]phenyl]sulfonylamino]-3-phenylpropanoic acid Chemical compound C([C@H](NS(=O)(=O)C1=CC=C(C=C1)C1=CC=C(C=C1)C=1C(=C2C=CC=CN2C=1)CCCC)C(O)=O)C1=CC=CC=C1 YAMKTWOCIRVYGC-HKBQPEDESA-N 0.000 claims description 2
• JBPANPVYVLBQAD-YTTGMZPUSA-N (2s)-2-[[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]-2-fluorophenyl]sulfonyl-methylamino]-3-phenylpropanoic acid Chemical compound C([C@H](N(C)S(=O)(=O)C=1C(=CC(=CC=1)C=1C=CC(=CC=1)C=1C2=CC=CC=C2OC=1CC=1C=CC=CC=1)F)C(O)=O)C1=CC=CC=C1 JBPANPVYVLBQAD-YTTGMZPUSA-N 0.000 claims description 2
• LJPVNLNUYKHZES-HKBQPEDESA-N (2s)-2-[[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]-2-fluorophenyl]sulfonylamino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NS(=O)(=O)C=1C(=CC(=CC=1)C=1C=CC(=CC=1)C=1C2=CC=CC=C2OC=1CC=1C=CC=CC=1)F)C1=CC=CC=C1 LJPVNLNUYKHZES-HKBQPEDESA-N 0.000 claims description 2
• YTZDCEHZTQGKTO-YTTGMZPUSA-N (2s)-2-[[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]benzoyl]-methylamino]-3-methylbutanoic acid Chemical compound C1=CC(C(=O)N(C)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=C(C=2C3=CC=CC=C3OC=2CC=2C=CC=CC=2)C=C1 YTZDCEHZTQGKTO-YTTGMZPUSA-N 0.000 claims description 2
• QEYCNFONUGAJSK-XIFFEERXSA-N (2s)-2-[[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]benzoyl]-methylamino]-3-phenylpropanoic acid Chemical compound C([C@H](N(C)C(=O)C=1C=CC(=CC=1)C=1C=CC(=CC=1)C=1C2=CC=CC=C2OC=1CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 QEYCNFONUGAJSK-XIFFEERXSA-N 0.000 claims description 2
• DBWYMVBSMCVXFS-YTTGMZPUSA-N (2s)-2-[[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]benzoyl]amino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=CC(=CC=1)C=1C=CC(=CC=1)C=1C2=CC=CC=C2OC=1CC=1C=CC=CC=1)C1=CC=CC=C1 DBWYMVBSMCVXFS-YTTGMZPUSA-N 0.000 claims description 2
• NHIMACVYYZIWJC-UMSFTDKQSA-N (2s)-2-[[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]phenyl]sulfonyl-ethylamino]-3-(4-fluorophenyl)propanoic acid Chemical compound C([C@H](N(CC)S(=O)(=O)C=1C=CC(=CC=1)C=1C=CC(=CC=1)C=1C2=CC=CC=C2OC=1CC=1C=CC=CC=1)C(O)=O)C1=CC=C(F)C=C1 NHIMACVYYZIWJC-UMSFTDKQSA-N 0.000 claims description 2
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• ZRECXQDSNGZOPR-XIFFEERXSA-N (2s)-2-[[4-[4-(2-benzyl-1-benzofuran-3-yl)phenyl]phenyl]sulfonyl-methylamino]-3-(4-fluorophenyl)propanoic acid Chemical compound C([C@H](N(C)S(=O)(=O)C=1C=CC(=CC=1)C=1C=CC(=CC=1)C=1C2=CC=CC=C2OC=1CC=1C=CC=CC=1)C(O)=O)C1=CC=C(F)C=C1 ZRECXQDSNGZOPR-XIFFEERXSA-N 0.000 claims description 2
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