JP2005521642A - 置換ヘテロアリールアルカン酸及びそのアルドースレダクターゼ阻害剤としての使用 - Google Patents
置換ヘテロアリールアルカン酸及びそのアルドースレダクターゼ阻害剤としての使用 Download PDFInfo
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- JP2005521642A JP2005521642A JP2003545652A JP2003545652A JP2005521642A JP 2005521642 A JP2005521642 A JP 2005521642A JP 2003545652 A JP2003545652 A JP 2003545652A JP 2003545652 A JP2003545652 A JP 2003545652A JP 2005521642 A JP2005521642 A JP 2005521642A
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- Prior art keywords
- alkyl
- halogen
- hydroxy
- compound
- haloalkyl
- 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.)
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- 239000002253 acid Substances 0.000 title abstract description 12
- 150000007513 acids Chemical class 0.000 title abstract description 4
- 239000003288 aldose reductase inhibitor Substances 0.000 title description 5
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 351
- 238000000034 method Methods 0.000 claims abstract description 67
- 238000011282 treatment Methods 0.000 claims abstract description 23
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 230000001684 chronic effect Effects 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims description 155
- 229910052739 hydrogen Inorganic materials 0.000 claims description 155
- 229910052736 halogen Inorganic materials 0.000 claims description 146
- 150000002367 halogens Chemical class 0.000 claims description 146
- -1 hydroxy, amino Chemical group 0.000 claims description 146
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 122
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 114
- 125000003118 aryl group Chemical group 0.000 claims description 95
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 82
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 67
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 62
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 59
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 49
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 48
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 44
- 125000005179 haloacetyl group Chemical group 0.000 claims description 44
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 41
- 150000002148 esters Chemical class 0.000 claims description 41
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 39
- 125000001153 fluoro group Chemical group F* 0.000 claims description 39
- 229910052717 sulfur Inorganic materials 0.000 claims description 38
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 38
- 125000005862 (C1-C6)alkanoyl group Chemical group 0.000 claims description 37
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 32
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 30
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 30
- 239000011593 sulfur Substances 0.000 claims description 30
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 claims description 29
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 claims description 29
- 229940116269 uric acid Drugs 0.000 claims description 29
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- 125000001072 heteroaryl group Chemical group 0.000 claims description 26
- 125000003282 alkyl amino group Chemical group 0.000 claims description 25
- 125000004995 haloalkylthio group Chemical group 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- 125000004414 alkyl thio group Chemical group 0.000 claims description 21
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 20
- 125000006771 (C1-C6) haloalkylthio group Chemical group 0.000 claims description 19
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 19
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 19
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 18
- 125000001188 haloalkyl group Chemical group 0.000 claims description 17
- 125000004076 pyridyl group Chemical group 0.000 claims description 17
- 125000002541 furyl group Chemical group 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 125000001544 thienyl group Chemical group 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000001246 bromo group Chemical group Br* 0.000 claims description 11
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 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
- 201000005569 Gout Diseases 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 9
- 125000001589 carboacyl group Chemical group 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 125000005605 benzo group Chemical group 0.000 claims description 8
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 7
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 7
- IEVFQDJUDLCOQY-UHFFFAOYSA-N 2-(3-((4,5,7-trifluorobenzo[d]thiazol-2-yl)methyl)-1h-pyrrolo[2,3-b]pyridin-1-yl)acetic acid Chemical compound C12=CC=CN=C2N(CC(=O)O)C=C1CC1=NC2=C(F)C(F)=CC(F)=C2S1 IEVFQDJUDLCOQY-UHFFFAOYSA-N 0.000 claims description 6
- OOBMLQZEXUXQJJ-UHFFFAOYSA-N 2-[5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]thiophen-2-yl]acetic acid Chemical compound S1C(CC(=O)O)=CC=C1CC1=NC2=C(F)C(F)=CC(F)=C2S1 OOBMLQZEXUXQJJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000005541 ACE inhibitor Substances 0.000 claims description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 6
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- CAPJMFWBLOUGMW-UHFFFAOYSA-N 2-[2-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]thiophen-3-yl]acetic acid Chemical compound C1=CSC(CC=2SC3=C(F)C=C(F)C(F)=C3N=2)=C1CC(=O)O CAPJMFWBLOUGMW-UHFFFAOYSA-N 0.000 claims description 5
- SKEWILPHFSWLSN-UHFFFAOYSA-N 2-[4-ethyl-2,6-dimethyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetic acid Chemical compound CCC1=C(CC(O)=O)C(C)=NC(C)=C1CC1=NC2=C(F)C(F)=CC(F)=C2S1 SKEWILPHFSWLSN-UHFFFAOYSA-N 0.000 claims description 5
- JWXQDSJKVIYMHR-UHFFFAOYSA-N 2-[6-methyl-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyrrolo[2,3-b]pyridin-1-yl]acetic acid Chemical compound FC1=CC(F)=C2SC(CC=3C4=CC=C(N=C4N(CC(O)=O)C=3)C)=NC2=C1F JWXQDSJKVIYMHR-UHFFFAOYSA-N 0.000 claims description 5
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 210000002966 serum Anatomy 0.000 claims description 5
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 5
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 4
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 4
- PFNREKUNOGSYRJ-UHFFFAOYSA-N 2-[2,4,6-trimethyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetic acid Chemical compound CC1=C(CC(O)=O)C(C)=NC(C)=C1CC1=NC2=C(F)C(F)=CC(F)=C2S1 PFNREKUNOGSYRJ-UHFFFAOYSA-N 0.000 claims description 4
- ZEYIZFXZZQJPGA-UHFFFAOYSA-N 2-[2,5-dimethyl-4-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]thiophen-3-yl]acetic acid Chemical compound OC(=O)CC1=C(C)SC(C)=C1CC1=NC2=C(F)C(F)=CC(F)=C2S1 ZEYIZFXZZQJPGA-UHFFFAOYSA-N 0.000 claims description 4
- XLAFRLAIBZTXCU-UHFFFAOYSA-N 2-[2-ethyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(CC)=NC=C1CC1=NC2=C(F)C(F)=CC(F)=C2S1 XLAFRLAIBZTXCU-UHFFFAOYSA-N 0.000 claims description 4
- PNWUIMAVAPWGSW-UHFFFAOYSA-N 2-[2-phenyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetic acid Chemical compound OC(=O)CC1=CC(CC=2SC3=C(F)C=C(F)C(F)=C3N=2)=CN=C1C1=CC=CC=C1 PNWUIMAVAPWGSW-UHFFFAOYSA-N 0.000 claims description 4
- AWRSPKGLQVNFPD-UHFFFAOYSA-N 2-[4-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]thiophen-2-yl]acetic acid Chemical compound S1C(CC(=O)O)=CC(CC=2SC3=C(F)C=C(F)C(F)=C3N=2)=C1 AWRSPKGLQVNFPD-UHFFFAOYSA-N 0.000 claims description 4
- LMPBXDVGTLTTAA-UHFFFAOYSA-N 2-[4-methyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]thiophen-3-yl]acetic acid Chemical compound OC(=O)CC1=CSC(CC=2SC3=C(F)C=C(F)C(F)=C3N=2)=C1C LMPBXDVGTLTTAA-UHFFFAOYSA-N 0.000 claims description 4
- KBKBWRFRCGROQC-UHFFFAOYSA-N 2-[5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetic acid Chemical compound OC(=O)CC1=CN=CC(CC=2SC3=C(F)C=C(F)C(F)=C3N=2)=C1 KBKBWRFRCGROQC-UHFFFAOYSA-N 0.000 claims description 4
- URZYTJCGTHKZPQ-UHFFFAOYSA-N 2-[6-ethyl-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyrrolo[2,3-b]pyridin-1-yl]acetic acid Chemical compound FC1=CC(F)=C2SC(CC=3C4=CC=C(N=C4N(CC(O)=O)C=3)CC)=NC2=C1F URZYTJCGTHKZPQ-UHFFFAOYSA-N 0.000 claims description 4
- 206010007749 Cataract diabetic Diseases 0.000 claims description 4
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 4
- 201000007025 diabetic cataract Diseases 0.000 claims description 4
- 125000002346 iodo group Chemical group I* 0.000 claims description 4
- 230000007823 neuropathy Effects 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
- ZYNSHYPZQCKSSY-UHFFFAOYSA-N 2-[2,6-diphenyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetic acid Chemical compound OC(=O)CC1=CC(CC=2SC3=C(F)C=C(F)C(F)=C3N=2)=C(C=2C=CC=CC=2)N=C1C1=CC=CC=C1 ZYNSHYPZQCKSSY-UHFFFAOYSA-N 0.000 claims description 3
- CTMUUQDXBYFSQW-UHFFFAOYSA-N 2-[2-benzyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetic acid Chemical compound OC(=O)CC1=CC(CC=2SC3=C(F)C=C(F)C(F)=C3N=2)=CN=C1CC1=CC=CC=C1 CTMUUQDXBYFSQW-UHFFFAOYSA-N 0.000 claims description 3
- CTIUPEXZVKFZKN-UHFFFAOYSA-N 2-[6-phenyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetic acid Chemical compound N=1C2=C(F)C(F)=CC(F)=C2SC=1CC1=CC(CC(=O)O)=CN=C1C1=CC=CC=C1 CTIUPEXZVKFZKN-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 3
- 125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 3
- 229930192474 thiophene Natural products 0.000 claims description 3
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- HYERUDTVJABLSF-UHFFFAOYSA-N 2-[2,6-diethyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(CC)=NC(CC)=C1CC1=NC2=C(F)C(F)=CC(F)=C2S1 HYERUDTVJABLSF-UHFFFAOYSA-N 0.000 claims description 2
- SGWFOCMKXJYHKO-UHFFFAOYSA-N 2-[2,6-dimethyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(C)=NC(C)=C1CC1=NC2=C(F)C(F)=CC(F)=C2S1 SGWFOCMKXJYHKO-UHFFFAOYSA-N 0.000 claims description 2
- OEORDSXPWKPIKP-UHFFFAOYSA-N 2-[2-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1,3-thiazol-4-yl]acetic acid Chemical compound OC(=O)CC1=CSC(CC=2SC3=C(F)C=C(F)C(F)=C3N=2)=N1 OEORDSXPWKPIKP-UHFFFAOYSA-N 0.000 claims description 2
- QERNHAPUCRXMGR-UHFFFAOYSA-N 2-[2-phenoxy-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetic acid Chemical compound OC(=O)CC1=CC(CC=2SC3=C(F)C=C(F)C(F)=C3N=2)=CN=C1OC1=CC=CC=C1 QERNHAPUCRXMGR-UHFFFAOYSA-N 0.000 claims description 2
- FRMQGFMUXLWFGM-UHFFFAOYSA-N 2-[3-methyl-4-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]thiophen-2-yl]acetic acid Chemical compound S1C(CC(O)=O)=C(C)C(CC=2SC3=C(F)C=C(F)C(F)=C3N=2)=C1 FRMQGFMUXLWFGM-UHFFFAOYSA-N 0.000 claims description 2
- JLCZMVMDODLRLV-UHFFFAOYSA-N 2-[5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]thiophen-3-yl]acetic acid Chemical compound OC(=O)CC1=CSC(CC=2SC3=C(F)C=C(F)C(F)=C3N=2)=C1 JLCZMVMDODLRLV-UHFFFAOYSA-N 0.000 claims description 2
- BPQXOOHODIRJJK-UHFFFAOYSA-N 2-[6-benzyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetic acid Chemical compound N=1C2=C(F)C(F)=CC(F)=C2SC=1CC1=CC(CC(=O)O)=CN=C1CC1=CC=CC=C1 BPQXOOHODIRJJK-UHFFFAOYSA-N 0.000 claims description 2
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical group C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- KXNQKOAQSGJCQU-UHFFFAOYSA-N benzo[e][1,3]benzothiazole Chemical compound C1=CC=C2C(N=CS3)=C3C=CC2=C1 KXNQKOAQSGJCQU-UHFFFAOYSA-N 0.000 claims description 2
- WMUIZUWOEIQJEH-UHFFFAOYSA-N benzo[e][1,3]benzoxazole Chemical compound C1=CC=C2C(N=CO3)=C3C=CC2=C1 WMUIZUWOEIQJEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- VMWHCGCGFKMESD-UHFFFAOYSA-N methyl 2-[4-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]thiophen-2-yl]acetate Chemical compound S1C(CC(=O)OC)=CC(CC=2SC3=C(F)C=C(F)C(F)=C3N=2)=C1 VMWHCGCGFKMESD-UHFFFAOYSA-N 0.000 claims description 2
- YWUKPLDSOFPSDV-UHFFFAOYSA-N methyl 2-[4-methyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]thiophen-3-yl]acetate Chemical compound COC(=O)CC1=CSC(CC=2SC3=C(F)C=C(F)C(F)=C3N=2)=C1C YWUKPLDSOFPSDV-UHFFFAOYSA-N 0.000 claims description 2
- GKPIPLHDIIPTES-UHFFFAOYSA-N methyl 2-[6-benzyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetate Chemical compound N=1C2=C(F)C(F)=CC(F)=C2SC=1CC1=CC(CC(=O)OC)=CN=C1CC1=CC=CC=C1 GKPIPLHDIIPTES-UHFFFAOYSA-N 0.000 claims description 2
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- KDZASNPOEXNJBZ-UHFFFAOYSA-N thieno[2,3-d][1,2]thiazole Chemical compound S1N=CC2=C1C=CS2 KDZASNPOEXNJBZ-UHFFFAOYSA-N 0.000 claims description 2
- ONCNIMLKGZSAJT-UHFFFAOYSA-N thieno[3,2-b]furan Chemical group S1C=CC2=C1C=CO2 ONCNIMLKGZSAJT-UHFFFAOYSA-N 0.000 claims description 2
- VJYJJHQEVLEOFL-UHFFFAOYSA-N thieno[3,2-b]thiophene Chemical group S1C=CC2=C1C=CS2 VJYJJHQEVLEOFL-UHFFFAOYSA-N 0.000 claims description 2
- OVCXRBARSPBVMC-UHFFFAOYSA-N triazolopyridine Chemical group C=1N2C(C(C)C)=NN=C2C=CC=1C=1OC=NC=1C1=CC=C(F)C=C1 OVCXRBARSPBVMC-UHFFFAOYSA-N 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 58
- QMJVDEUOIVQWQD-UHFFFAOYSA-N 2-[2,6-dipropyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(CCC)=NC(CCC)=C1CC1=NC2=C(F)C(F)=CC(F)=C2S1 QMJVDEUOIVQWQD-UHFFFAOYSA-N 0.000 claims 1
- HJUMIRGVLXWEGT-UHFFFAOYSA-N 2-[6-ethyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetic acid Chemical compound CCC1=NC=C(CC(O)=O)C=C1CC1=NC2=C(F)C(F)=CC(F)=C2S1 HJUMIRGVLXWEGT-UHFFFAOYSA-N 0.000 claims 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 1
- MCAIJPGUXQSZIP-UHFFFAOYSA-N methyl 2-[2,6-diethyl-5-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]pyridin-3-yl]acetate Chemical compound C1=C(CC(=O)OC)C(CC)=NC(CC)=C1CC1=NC2=C(F)C(F)=CC(F)=C2S1 MCAIJPGUXQSZIP-UHFFFAOYSA-N 0.000 claims 1
- 229960002324 trifluoperazine Drugs 0.000 claims 1
- 229920002554 vinyl polymer Polymers 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical class CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 262
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 142
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 112
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 110
- 239000000243 solution Substances 0.000 description 86
- 239000000203 mixture Substances 0.000 description 65
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 55
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- 230000029663 wound healing Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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 with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/26—Radicals substituted by halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/57—Nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D213/61—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/34—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D309/36—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
- C07D309/38—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms one oxygen atom in position 2 or 4, e.g. pyrones
-
- 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
- C07D417/06—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 carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Ophthalmology & Optometry (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33605501P | 2001-11-15 | 2001-11-15 | |
| US37862602P | 2002-05-07 | 2002-05-07 | |
| PCT/US2002/036709 WO2003044015A2 (en) | 2001-11-15 | 2002-11-15 | Substituted heteroarylalkanoic acids and their use as aldose reductase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005521642A true JP2005521642A (ja) | 2005-07-21 |
| JP2005521642A5 JP2005521642A5 (enExample) | 2006-01-19 |
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|---|---|---|---|
| JP2003545652A Pending JP2005521642A (ja) | 2001-11-15 | 2002-11-15 | 置換ヘテロアリールアルカン酸及びそのアルドースレダクターゼ阻害剤としての使用 |
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| Country | Link |
|---|---|
| US (2) | US7361671B2 (enExample) |
| EP (1) | EP1444228B1 (enExample) |
| JP (1) | JP2005521642A (enExample) |
| AT (1) | ATE396190T1 (enExample) |
| AU (1) | AU2002350191A1 (enExample) |
| CA (1) | CA2466925A1 (enExample) |
| DE (1) | DE60226764D1 (enExample) |
| MX (1) | MXPA04004548A (enExample) |
| TW (1) | TW200303198A (enExample) |
| WO (1) | WO2003044015A2 (enExample) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
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| ATE435202T1 (de) | 2002-01-11 | 2009-07-15 | Daiichi Sankyo Co Ltd | Aminoalkoholderivat oder phosphonsäurederivat und diese enthaltende medizinische zusammensetzung |
| GB0302094D0 (en) | 2003-01-29 | 2003-02-26 | Pharmagene Lab Ltd | EP4 receptor antagonists |
| GB0324269D0 (en) | 2003-10-16 | 2003-11-19 | Pharmagene Lab Ltd | EP4 receptor antagonists |
| CN1921847B (zh) | 2004-02-24 | 2010-06-16 | 三共株式会社 | 氨基醇化合物 |
| WO2005118166A2 (en) | 2004-06-04 | 2005-12-15 | Teva Pharmaceutical Industries, Ltd. | Pharmaceutical composition containing irbesartan |
| KR100958830B1 (ko) * | 2004-09-03 | 2010-05-24 | 주식회사유한양행 | 피롤로[2,3-c]피리딘 유도체 및 그의 제조방법 |
| CA2579083C (en) | 2004-09-03 | 2011-06-14 | Yuhan Corporation | Pyrrolo[3,2-c]pyridine derivatives and processes for the preparation thereof |
| FR2876103B1 (fr) * | 2004-10-01 | 2008-02-22 | Aventis Pharma Sa | Nouveaux derives bis-azaindoles, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de kinases |
| GB2422829A (en) * | 2005-02-04 | 2006-08-09 | Oxagen Ltd | Pyrrolopyridines and their use in the treatment of diseases mediated by PGD2 at the CRTH2 receptor |
| GB2422830A (en) * | 2005-02-04 | 2006-08-09 | Oxagen Ltd | Pyrrolopyridines and their use in the treatment of diseases mediated by PGD2 at the CRTH2 receptor |
| GB2422831A (en) * | 2005-02-04 | 2006-08-09 | Oxagen Ltd | Pyrrolopyridines and their use in the treatment of diseases mediated by PGD2 at the CRTH2 receptor |
| US7589213B2 (en) * | 2007-04-27 | 2009-09-15 | Old David W | Therapeutic substituted lactams |
| WO2010071865A1 (en) | 2008-12-19 | 2010-06-24 | Nuon Therapeutics, Inc. | Pharmaceutical compositions and methods for treating hyperuricemia and related disorders |
| US20100160351A1 (en) * | 2008-12-19 | 2010-06-24 | Nuon Therapeutics, Inc. | Pharmaceutical compositions and methods for treating hyperuricemia and related disorders |
| KR101903354B1 (ko) | 2009-06-17 | 2018-10-04 | 버텍스 파마슈티칼스 인코포레이티드 | 인플루엔자 바이러스 복제의 억제제 |
| WO2011032175A1 (en) | 2009-09-14 | 2011-03-17 | Nuon Therapeutics, Inc. | Combination formulations of tranilast and allopurinol and methods related thereto |
| EP2512247B1 (en) | 2009-12-16 | 2014-06-04 | N30 Pharmaceuticals, Inc. | Novel thiophene inhibitors of s-nitrosoglutathione reductase |
| EP2651940A1 (en) | 2010-12-16 | 2013-10-23 | Vertex Pharmaceuticals Incorporated | Inhibitors of influenza viruses replication |
| UA118010C2 (uk) | 2011-08-01 | 2018-11-12 | Вертекс Фармасьютікалз Інкорпорейтед | Інгібітори реплікації вірусів грипу |
| AR095883A1 (es) | 2013-04-18 | 2015-11-18 | Astellas Pharma Inc | Compuestos de acetamida heterocíclica |
| ES2684755T3 (es) | 2013-11-13 | 2018-10-04 | Vertex Pharmaceuticals Incorporated | Métodos para preparar inhibidores de la replicación de virus de la gripe |
| DK3068776T3 (da) | 2013-11-13 | 2019-07-29 | Vertex Pharma | Inhibitorer af replikation af influenzavira |
| CN112961149A (zh) | 2014-08-11 | 2021-06-15 | 安吉恩生物医药公司 | 细胞色素p450抑制剂及其用途 |
| CN107531631B (zh) | 2014-12-31 | 2021-09-03 | 安吉昂生物医药公司 | 用于治疗疾病的方法和药剂 |
| US10562844B2 (en) | 2015-01-26 | 2020-02-18 | Wake Forest University Health Sciences | HYPDH inhibitors and methods of use for the treatment of kidney stones |
| WO2016135630A1 (en) * | 2015-02-25 | 2016-09-01 | Sabic Global Technologies B.V. | Process for removing impurities from acetic acid |
| WO2016183120A1 (en) | 2015-05-13 | 2016-11-17 | Vertex Pharmaceuticals Incorporated | Inhibitors of influenza viruses replication |
| WO2016183116A1 (en) | 2015-05-13 | 2016-11-17 | Vertex Pharmaceuticals Incorporated | Methods of preparing inhibitors of influenza viruses replication |
| MX2018001073A (es) | 2015-08-06 | 2018-06-12 | Chimerix Inc | Nucleosidos de pirrolopirimidina y analogos de los mismos utiles como agentes antivirales. |
| WO2019060692A1 (en) | 2017-09-21 | 2019-03-28 | Chimerix, Inc. | MORPHIC FORMS OF 4-AMINO-7- (3,4-DIHYDROXY-5- (HYDROXYMETHYL) -ETRAHYDROFURAN-2-YL) -2-METHYL-7H-PYRROLO [2,3-D] PYRIMIDINE-5-CARBOXAMIDE AND THEIR USES |
| WO2019226213A2 (en) | 2018-03-08 | 2019-11-28 | Incyte Corporation | AMINOPYRAZINE DIOL COMPOUNDS AS PI3K-y INHIBITORS |
| WO2020010003A1 (en) | 2018-07-02 | 2020-01-09 | Incyte Corporation | AMINOPYRAZINE DERIVATIVES AS PI3K-γ INHIBITORS |
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| AR208397A1 (es) * | 1973-02-20 | 1976-12-27 | Ciba Geigy Ag | Procedimiento para la elaboracion de compuestos de 1-piridiloxi-2-hidroxi-3-amino-propano1-piraziniloxi-2-hidroxi-3-amino-propano y 1-pirimidiniloxi-2-hidroxi-3-amino-propan |
| AU4226493A (en) * | 1992-05-01 | 1993-11-29 | Smithkline Beecham Corporation | Leukotriene antagonists |
| MA22926A1 (fr) * | 1992-06-30 | 1994-04-01 | Smithkline Beecham Corp | Procede pour la preparation de nouveaux composes. |
| DK1217001T3 (da) * | 1999-09-28 | 2006-03-20 | Eisai Co Ltd | Quinuclidinforbindelser og lægemidler indeholdende dem som den aktive bestanddel |
| JP5036112B2 (ja) * | 1999-10-06 | 2012-09-26 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | チロシンキナーゼのインヒビターとして有益な複素環化合物 |
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2002
- 2002-11-14 US US10/295,414 patent/US7361671B2/en not_active Expired - Fee Related
- 2002-11-15 AT AT02786720T patent/ATE396190T1/de not_active IP Right Cessation
- 2002-11-15 TW TW091133509A patent/TW200303198A/zh unknown
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- 2002-11-15 JP JP2003545652A patent/JP2005521642A/ja active Pending
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- 2002-11-15 WO PCT/US2002/036709 patent/WO2003044015A2/en not_active Ceased
- 2002-11-15 MX MXPA04004548A patent/MXPA04004548A/es not_active Application Discontinuation
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2008
- 2008-04-22 US US12/107,740 patent/US20090163535A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
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| EP1444228A2 (en) | 2004-08-11 |
| WO2003044015A2 (en) | 2003-05-30 |
| US20090163535A1 (en) | 2009-06-25 |
| ATE396190T1 (de) | 2008-06-15 |
| AU2002350191A8 (en) | 2003-06-10 |
| MXPA04004548A (es) | 2004-09-10 |
| TW200303198A (en) | 2003-09-01 |
| EP1444228B1 (en) | 2008-05-21 |
| AU2002350191A1 (en) | 2003-06-10 |
| CA2466925A1 (en) | 2003-05-30 |
| WO2003044015A3 (en) | 2003-10-02 |
| US7361671B2 (en) | 2008-04-22 |
| DE60226764D1 (de) | 2008-07-03 |
| US20030166668A1 (en) | 2003-09-04 |
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