OA11622A - Substituted indolealkanoic acids. - Google Patents
Substituted indolealkanoic acids. Download PDFInfo
- Publication number
- OA11622A OA11622A OA1200000269A OA1200000269A OA11622A OA 11622 A OA11622 A OA 11622A OA 1200000269 A OA1200000269 A OA 1200000269A OA 1200000269 A OA1200000269 A OA 1200000269A OA 11622 A OA11622 A OA 11622A
- Authority
- OA
- OAPI
- Prior art keywords
- compound according
- methyl
- indole
- acetic acid
- alkyl
- Prior art date
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- 239000002253 acid Substances 0.000 title claims abstract description 13
- 150000007513 acids Chemical class 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 113
- 238000000034 method Methods 0.000 claims abstract description 35
- -1 4-imidazolyl Chemical group 0.000 claims description 94
- 125000000217 alkyl group Chemical group 0.000 claims description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims description 52
- 239000001257 hydrogen Substances 0.000 claims description 51
- 125000001153 fluoro group Chemical group F* 0.000 claims description 50
- 229910052736 halogen Inorganic materials 0.000 claims description 50
- 150000002367 halogens Chemical group 0.000 claims description 50
- 239000000203 mixture Substances 0.000 claims description 47
- 125000003545 alkoxy group Chemical group 0.000 claims description 37
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 35
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 35
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 33
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 31
- 125000000623 heterocyclic group Chemical group 0.000 claims description 22
- 125000003282 alkyl amino group Chemical group 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 125000001246 bromo group Chemical group Br* 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 16
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 15
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 125000005605 benzo group Chemical group 0.000 claims description 13
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 13
- 239000001301 oxygen Substances 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 235000019000 fluorine Nutrition 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 7
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 239000000651 prodrug Chemical group 0.000 claims description 6
- 229940002612 prodrug Drugs 0.000 claims description 6
- 239000011593 sulfur Substances 0.000 claims description 6
- MGICLRNAZXDKAT-UHFFFAOYSA-N 2-(2-methylindol-1-yl)acetic acid Chemical compound C1=CC=C2N(CC(O)=O)C(C)=CC2=C1 MGICLRNAZXDKAT-UHFFFAOYSA-N 0.000 claims description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
- 239000005977 Ethylene Substances 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 4
- VFRYWFLFAVFXIO-UHFFFAOYSA-N 2-[2-methyl-6-morpholin-4-yl-3-(4,5,7-trifluoro-1,3-benzothiazol-2-yl)indol-1-yl]acetic acid Chemical compound C1=C2N(CC(O)=O)C(C)=C(C=3SC4=C(F)C=C(F)C(F)=C4N=3)C2=CC=C1N1CCOCC1 VFRYWFLFAVFXIO-UHFFFAOYSA-N 0.000 claims description 3
- DFSHWYWKHTUEAJ-UHFFFAOYSA-N 2-[5-fluoro-2-methyl-3-(4,5,7-trifluoro-1,3-benzothiazol-2-yl)indol-1-yl]acetic acid Chemical compound C12=CC(F)=CC=C2N(CC(O)=O)C(C)=C1C1=NC2=C(F)C(F)=CC(F)=C2S1 DFSHWYWKHTUEAJ-UHFFFAOYSA-N 0.000 claims description 3
- HHQZYRNRGYRKKF-UHFFFAOYSA-N 2-[5-morpholin-4-yl-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid Chemical compound C=1C=C2N(CC(=O)O)C=C(CC=3SC4=C(F)C=C(F)C(F)=C4N=3)C2=CC=1N1CCOCC1 HHQZYRNRGYRKKF-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
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 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
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000002346 iodo group Chemical group I* 0.000 claims description 3
- VBNFGLWTIQTREP-UHFFFAOYSA-N 2-[2-methyl-3-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]indol-1-yl]acetic acid Chemical compound C12=CC=CC=C2N(CC(O)=O)C(C)=C1C1=NC2=CC(C(F)(F)F)=CC=C2S1 VBNFGLWTIQTREP-UHFFFAOYSA-N 0.000 claims description 2
- CUNNSKIRHRLJMS-UHFFFAOYSA-N 2-[4-methyl-2-phenyl-3-(4,5,7-trifluoro-1,3-benzothiazol-2-yl)indol-1-yl]acetic acid Chemical compound N=1C2=C(F)C(F)=CC(F)=C2SC=1C=1C=2C(C)=CC=CC=2N(CC(O)=O)C=1C1=CC=CC=C1 CUNNSKIRHRLJMS-UHFFFAOYSA-N 0.000 claims description 2
- LJTZOVSFODOIIV-UHFFFAOYSA-N 2-[5-chloro-2-methyl-3-(4,5,7-trifluoro-1,3-benzothiazol-2-yl)indol-1-yl]acetic acid Chemical compound C12=CC(Cl)=CC=C2N(CC(O)=O)C(C)=C1C1=NC2=C(F)C(F)=CC(F)=C2S1 LJTZOVSFODOIIV-UHFFFAOYSA-N 0.000 claims description 2
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims description 2
- 208000017442 Retinal disease Diseases 0.000 claims description 2
- 206010038923 Retinopathy Diseases 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
- 208000017169 kidney disease Diseases 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 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 compound S1C=CC2=C1C=CO2 ONCNIMLKGZSAJT-UHFFFAOYSA-N 0.000 claims description 2
- VJYJJHQEVLEOFL-UHFFFAOYSA-N thieno[3,2-b]thiophene Chemical compound S1C=CC2=C1C=CS2 VJYJJHQEVLEOFL-UHFFFAOYSA-N 0.000 claims description 2
- 229930192474 thiophene Natural products 0.000 claims description 2
- OVCXRBARSPBVMC-UHFFFAOYSA-N triazolopyridine Chemical compound 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
- SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- CKTQUOAACPEOFU-UHFFFAOYSA-N 2-[2,6-dimethyl-3-(4,5,7-trifluoro-1,3-benzothiazol-2-yl)indol-1-yl]acetic acid Chemical compound C12=CC=C(C)C=C2N(CC(O)=O)C(C)=C1C1=NC2=C(F)C(F)=CC(F)=C2S1 CKTQUOAACPEOFU-UHFFFAOYSA-N 0.000 claims 1
- OVRDKEPIWAYWQW-UHFFFAOYSA-N 2-[6-chloro-2-methyl-3-(4,5,7-trifluoro-1,3-benzothiazol-2-yl)indol-1-yl]acetic acid Chemical compound C12=CC=C(Cl)C=C2N(CC(O)=O)C(C)=C1C1=NC2=C(F)C(F)=CC(F)=C2S1 OVRDKEPIWAYWQW-UHFFFAOYSA-N 0.000 claims 1
- HMVAUYQQSPIFND-UHFFFAOYSA-N 2-[7-fluoro-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid Chemical compound C12=CC=CC(F)=C2N(CC(=O)O)C=C1CC1=NC2=C(F)C(F)=CC(F)=C2S1 HMVAUYQQSPIFND-UHFFFAOYSA-N 0.000 claims 1
- 208000002177 Cataract Diseases 0.000 claims 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims 1
- PITCTBFYPGWOKF-UHFFFAOYSA-N ethyl 2-[3-[(3-nitrophenyl)methyl]indol-1-yl]acetate Chemical compound C12=CC=CC=C2N(CC(=O)OCC)C=C1CC1=CC=CC([N+]([O-])=O)=C1 PITCTBFYPGWOKF-UHFFFAOYSA-N 0.000 claims 1
- 125000006501 nitrophenyl group Chemical group 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 15
- 230000015572 biosynthetic process Effects 0.000 abstract description 13
- 230000001684 chronic effect Effects 0.000 abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 60
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 46
- 238000005481 NMR spectroscopy Methods 0.000 description 41
- 235000019439 ethyl acetate Nutrition 0.000 description 39
- 239000000243 solution Substances 0.000 description 38
- 150000002431 hydrogen Chemical group 0.000 description 29
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
- MYTGFBZJLDLWQG-UHFFFAOYSA-N 5-chloro-1h-indole Chemical compound ClC1=CC=C2NC=CC2=C1 MYTGFBZJLDLWQG-UHFFFAOYSA-N 0.000 description 19
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000000543 intermediate Substances 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 17
- 229940093499 ethyl acetate Drugs 0.000 description 17
- 229910001868 water Inorganic materials 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 150000002475 indoles Chemical class 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 239000000463 material Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 102000016912 Aldehyde Reductase Human genes 0.000 description 8
- 108010053754 Aldehyde reductase Proteins 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 102000004316 Oxidoreductases Human genes 0.000 description 7
- 108090000854 Oxidoreductases Proteins 0.000 description 7
- 239000003288 aldose reductase inhibitor Substances 0.000 description 7
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 235000011054 acetic acid Nutrition 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 238000007429 general method Methods 0.000 description 6
- 125000001041 indolyl group Chemical group 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 208000002249 Diabetes Complications Diseases 0.000 description 5
- 206010012655 Diabetic complications Diseases 0.000 description 5
- 229910004373 HOAc Inorganic materials 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- OCDGBSUVYYVKQZ-UHFFFAOYSA-N beta-dimethylaminomethylindole Natural products C1=CC=C2C(CN(C)C)=CNC2=C1 OCDGBSUVYYVKQZ-UHFFFAOYSA-N 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 150000001768 cations Chemical class 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 239000000796 flavoring agent Substances 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- RREODNYNAPILHF-UHFFFAOYSA-N 2-amino-3,4,6-trifluorobenzenethiol;hydrochloride Chemical compound Cl.NC1=C(F)C(F)=CC(F)=C1S RREODNYNAPILHF-UHFFFAOYSA-N 0.000 description 4
- JHFOWEGCZWLHNW-UHFFFAOYSA-N 4-fluoro-2-methyl-1-nitrobenzene Chemical compound CC1=CC(F)=CC=C1[N+]([O-])=O JHFOWEGCZWLHNW-UHFFFAOYSA-N 0.000 description 4
- ONYNOPPOVKYGRS-UHFFFAOYSA-N 6-methylindole Natural products CC1=CC=C2C=CNC2=C1 ONYNOPPOVKYGRS-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
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- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
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- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
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- 239000008159 sesame oil Substances 0.000 description 1
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- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
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- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
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Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Ophthalmology & Optometry (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8014398P | 1998-03-31 | 1998-03-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| OA11622A true OA11622A (en) | 2004-09-16 |
Family
ID=22155536
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| OA1200000269A OA11622A (en) | 1998-03-31 | 1999-03-31 | Substituted indolealkanoic acids. |
Country Status (29)
| Country | Link |
|---|---|
| US (9) | US6214991B1 (cs) |
| EP (1) | EP1066283B1 (cs) |
| JP (2) | JP3494990B2 (cs) |
| KR (1) | KR100584650B1 (cs) |
| CN (1) | CN1205207C (cs) |
| AP (1) | AP2000001929A0 (cs) |
| AT (1) | ATE269861T1 (cs) |
| AU (1) | AU774929B2 (cs) |
| BG (1) | BG65446B1 (cs) |
| BR (1) | BR9909358A (cs) |
| CA (1) | CA2383983C (cs) |
| CZ (1) | CZ300706B6 (cs) |
| DE (1) | DE69918278T2 (cs) |
| EE (1) | EE200000573A (cs) |
| ES (1) | ES2224632T3 (cs) |
| HU (1) | HUP0101672A3 (cs) |
| ID (1) | ID27884A (cs) |
| IL (2) | IL138711A0 (cs) |
| MX (1) | MXPA02003122A (cs) |
| NO (1) | NO20004900L (cs) |
| NZ (1) | NZ507172A (cs) |
| OA (1) | OA11622A (cs) |
| PL (1) | PL201645B1 (cs) |
| SK (1) | SK7522001A3 (cs) |
| TR (1) | TR200002869T2 (cs) |
| TW (1) | TWI243163B (cs) |
| WO (1) | WO1999050268A2 (cs) |
| YU (1) | YU59600A (cs) |
| ZA (1) | ZA200005577B (cs) |
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
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| ATE269861T1 (de) | 1998-03-31 | 2004-07-15 | Inst For Pharm Discovery Inc | Substituierte indolalkansäure |
| TNSN99224A1 (fr) * | 1998-12-01 | 2005-11-10 | Inst For Pharm Discovery Inc | Methodes de reduction des niveaux de glucose et triglyceride en serum et pour suppression de l'antigenese utilisant les acides la indolealkanoique |
| AU5960300A (en) * | 1999-07-15 | 2001-02-05 | Nps Allelix Corp. | Heterocyclic compounds for the treatment of migraine |
| WO2001064205A2 (en) * | 2000-03-02 | 2001-09-07 | The Institutes For Pharmaceutical Discovery, Llc | Compositions containing a substituted indolealkanoic acid and an angiotensin converting enzyme inhibitor |
| US20020012630A1 (en) * | 2000-05-09 | 2002-01-31 | James Nolan | Methods for testing compounds useful in treating diabetic complications |
| JP2004517851A (ja) | 2000-12-27 | 2004-06-17 | バイエル アクチェンゲゼルシャフト | 甲状腺受容体のリガンドとしてのインドール誘導体 |
| TWI224101B (en) | 2001-06-20 | 2004-11-21 | Wyeth Corp | Substituted naphthyl indole derivatives as inhibitors of plasminogen activator inhibitor type-1 (PAI-1) |
| WO2003000253A1 (en) | 2001-06-20 | 2003-01-03 | Wyeth | Substituted indole acid derivatives as inhibitors of plasminogen activator inhibitor-1 (pai-1) |
| EP1465629B1 (en) | 2002-01-18 | 2007-03-14 | Aryx Therapeutics | 5-ht3 receptor antagonists and methods of use |
| CA2395871A1 (en) * | 2002-07-26 | 2004-01-26 | The Institutes For Pharmaceutical Discovery, Llc | Substituted indolealkanoic acids derivatives and formulations containing same for use in treatment of diabetic complications |
| US20060100255A1 (en) * | 2002-07-26 | 2006-05-11 | Van Zandt Michael C | Substituted indolealkanoic acids derivative and formulations containing same for use in the treatment of diabetic complications |
| PT1537078E (pt) * | 2002-08-29 | 2010-06-18 | Merck Sharp & Dohme | Indoles que possuem actividade antidiabética |
| ES2266907T3 (es) | 2002-12-10 | 2007-03-01 | Wyeth | Derivados sustituidos del acido 3-carbonil-indol-1-il-acetico como inhibidor del activador del plasminogeno-1 (pal-1). |
| JP2006510673A (ja) | 2002-12-10 | 2006-03-30 | ワイス | プラスミノゲンアクティベータインヒビター１（ｐａｉ−１）のインヒビターとしての、アリール、アリールオキシ、および、アルキルオキシ置換１ｈ−インドール−３−イルグリオキシル酸誘導体 |
| DK1569899T3 (da) | 2002-12-10 | 2006-10-23 | Wyeth Corp | Substituerede 3-alkyl- og 3-arylalkyl-1H-indol-1-yl-eddikesyrederivater som inhibitorer af plasminogenaktivator-inhibitor-1 (PAI-1) |
| BR0316584A (pt) | 2002-12-10 | 2005-10-04 | Wyeth Corp | Derivados de ácido acético indol oxo-acetil amino substituìdo como inibidores do inibidor-1 do ativador do plasminogênio (pai-1) |
| UA80453C2 (en) | 2002-12-10 | 2007-09-25 | Derivatives of substituted dyhydropyranoindol-3,4-dion as inhibitors of plasminogen activator inhibitor-1 (pai-1) | |
| WO2004098498A2 (en) * | 2003-04-28 | 2004-11-18 | Bayer Pharmaceuticals Corporation | Indole acetic acid derivatives and their use as pharmaceutical agents |
| KR20060006953A (ko) * | 2003-04-30 | 2006-01-20 | 디 인스티튜트스 포 파마슈티컬 디스커버리, 엘엘씨 | 치환된 카르복실산 |
| ZA200600424B (en) * | 2003-08-01 | 2007-05-30 | Genelabs Tech Inc | Bicyclic imidazol derivatives against flaviviridae |
| US7265148B2 (en) | 2003-09-25 | 2007-09-04 | Wyeth | Substituted pyrrole-indoles |
| US7141592B2 (en) | 2003-09-25 | 2006-11-28 | Wyeth | Substituted oxadiazolidinediones |
| US7351726B2 (en) | 2003-09-25 | 2008-04-01 | Wyeth | Substituted oxadiazolidinediones |
| US7582773B2 (en) | 2003-09-25 | 2009-09-01 | Wyeth | Substituted phenyl indoles |
| US7411083B2 (en) | 2003-09-25 | 2008-08-12 | Wyeth | Substituted acetic acid derivatives |
| US7332521B2 (en) | 2003-09-25 | 2008-02-19 | Wyeth | Substituted indoles |
| US7446201B2 (en) | 2003-09-25 | 2008-11-04 | Wyeth | Substituted heteroaryl benzofuran acids |
| US7163954B2 (en) | 2003-09-25 | 2007-01-16 | Wyeth | Substituted naphthyl benzothiophene acids |
| US7268159B2 (en) | 2003-09-25 | 2007-09-11 | Wyeth | Substituted indoles |
| US7442805B2 (en) | 2003-09-25 | 2008-10-28 | Wyeth | Substituted sulfonamide-indoles |
| GB0324763D0 (en) | 2003-10-23 | 2003-11-26 | Oxagen Ltd | Use of compounds in therapy |
| EP1805136A1 (en) * | 2004-10-28 | 2007-07-11 | The Institutes for Pharmaceutical Discovery, LLC | Substituted phenylalkanoic acids |
| HRP20070342A2 (hr) * | 2005-01-14 | 2007-10-31 | Genelabs Technologies | Derivati indola za liječenje virusnih infekcija |
| GB0505048D0 (en) * | 2005-03-11 | 2005-04-20 | Oxagen Ltd | Compounds with PGD antagonist activity |
| US20080051384A1 (en) * | 2006-07-14 | 2008-02-28 | Genelabs Technologies, Inc. | Antiviral agents |
| KR20090042808A (ko) | 2006-07-22 | 2009-04-30 | 옥사겐 리미티드 | 씨알티에이치2 길항제 활성을 갖는 화합물 |
| RU2503672C2 (ru) | 2008-01-18 | 2014-01-10 | Оксаген Лимитед | Соединения, обладающие активностью антагонистов crth2 |
| US7750027B2 (en) * | 2008-01-18 | 2010-07-06 | Oxagen Limited | Compounds having CRTH2 antagonist activity |
| EP2240444A1 (en) * | 2008-01-22 | 2010-10-20 | Oxagen Limited | Compounds having crth2 antagonist activity |
| EP2265581A1 (en) * | 2008-01-22 | 2010-12-29 | Oxagen Limited | Compounds having crth2 antagonist activity |
| GB2457040A (en) * | 2008-01-30 | 2009-08-05 | Oxagen Ltd | 1-Acetic acid indole derivatives with PGD2 activity |
| EP2424521A4 (en) | 2009-04-29 | 2015-03-04 | Amarin Pharmaceuticals Ie Ltd | PHARMACEUTICAL COMPOSITIONS COMPRISING EPA AND CARDIOVASCULAR AGENT AND METHODS OF USE |
| US8916563B2 (en) | 2010-07-16 | 2014-12-23 | The Trustees Of Columbia University In The City Of New York | Aldose reductase inhibitors and uses thereof |
| ES2613700T3 (es) * | 2010-07-16 | 2017-05-25 | The Trustees Of Columbia University In The City Of New York | Inhibidores de la aldosa reductasa y usos de los mismos |
| GB201322273D0 (en) | 2013-12-17 | 2014-01-29 | Atopix Therapeutics Ltd | Process |
| GB201407820D0 (en) | 2014-05-02 | 2014-06-18 | Atopix Therapeutics Ltd | Polymorphic form |
| GB201407807D0 (en) | 2014-05-02 | 2014-06-18 | Atopix Therapeutics Ltd | Polymorphic form |
| CA3025081A1 (en) | 2016-06-21 | 2017-12-28 | The Trustees Of Columbia University In The City Of New York | Substituted 3,4-dihydrothieno [3,4-d]pyridazine compounds and use thereof as aldose reductase inhibitors |
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1999
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- 1999-03-31 DE DE69918278T patent/DE69918278T2/de not_active Expired - Lifetime
- 1999-03-31 SK SK752-2001A patent/SK7522001A3/sk not_active Application Discontinuation
- 1999-03-31 HU HU0101672A patent/HUP0101672A3/hu unknown
- 1999-03-31 WO PCT/US1999/007116 patent/WO1999050268A2/en active IP Right Grant
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- 1999-03-31 AP APAP/P/2000/001929A patent/AP2000001929A0/en unknown
- 1999-03-31 KR KR1020007010884A patent/KR100584650B1/ko not_active Expired - Fee Related
- 1999-03-31 BR BR9909358-8A patent/BR9909358A/pt not_active Application Discontinuation
- 1999-03-31 OA OA1200000269A patent/OA11622A/en unknown
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- 1999-03-31 TR TR2000/02869T patent/TR200002869T2/xx unknown
- 1999-03-31 AU AU34595/99A patent/AU774929B2/en not_active Ceased
- 1999-03-31 ID IDW20002212A patent/ID27884A/id unknown
- 1999-03-31 US US09/282,280 patent/US6214991B1/en not_active Expired - Fee Related
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- 2000-09-29 BG BG104819A patent/BG65446B1/bg unknown
- 2000-09-29 NO NO20004900A patent/NO20004900L/no not_active Application Discontinuation
- 2000-10-11 ZA ZA200005577A patent/ZA200005577B/en unknown
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- 2002-06-28 US US10/185,863 patent/US6730794B2/en not_active Expired - Fee Related
- 2002-10-02 JP JP2002290240A patent/JP2003155274A/ja active Pending
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- 2010-02-08 US US12/701,967 patent/US8163932B2/en not_active Expired - Fee Related
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