ES2274369T3 - Intermedios utiles para la sintesis de piridazinonas inhibidoras de aldosa reductasa. - Google Patents
Intermedios utiles para la sintesis de piridazinonas inhibidoras de aldosa reductasa. Download PDFInfo
- Publication number
- ES2274369T3 ES2274369T3 ES04023149T ES04023149T ES2274369T3 ES 2274369 T3 ES2274369 T3 ES 2274369T3 ES 04023149 T ES04023149 T ES 04023149T ES 04023149 T ES04023149 T ES 04023149T ES 2274369 T3 ES2274369 T3 ES 2274369T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- phenyl
- substituents
- alkoxy
- chloro
- 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.)
- Expired - Lifetime
Links
- 239000000543 intermediate Substances 0.000 title description 9
- 230000015572 biosynthetic process Effects 0.000 title description 5
- 238000003786 synthesis reaction Methods 0.000 title description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 65
- 239000002253 acid Substances 0.000 claims abstract description 62
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 62
- 150000003839 salts Chemical class 0.000 claims abstract description 54
- 125000001424 substituent group Chemical group 0.000 claims abstract description 47
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
- 239000001257 hydrogen Substances 0.000 claims abstract description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 17
- 239000000460 chlorine Substances 0.000 claims abstract description 15
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims abstract 2
- -1 cinolinyl Chemical group 0.000 claims description 227
- 150000001875 compounds Chemical class 0.000 claims description 145
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 52
- 125000001153 fluoro group Chemical group F* 0.000 claims description 45
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 42
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 40
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 32
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 22
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 21
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 21
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 21
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 20
- 125000001246 bromo group Chemical group Br* 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 125000000335 thiazolyl group Chemical group 0.000 claims description 17
- 125000002883 imidazolyl group Chemical group 0.000 claims description 16
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 16
- 125000002971 oxazolyl group Chemical group 0.000 claims description 16
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 12
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 12
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 12
- 125000002541 furyl group Chemical group 0.000 claims description 12
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 12
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 12
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 12
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 12
- 125000005493 quinolyl group Chemical group 0.000 claims description 12
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 12
- 125000001544 thienyl group Chemical group 0.000 claims description 12
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 11
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 11
- 125000004534 benzothien-2-yl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 11
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 11
- 125000001425 triazolyl group Chemical group 0.000 claims description 11
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 10
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 9
- 125000005554 pyridyloxy group Chemical group 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 125000004536 indazol-1-yl group Chemical group N1(N=CC2=CC=CC=C12)* 0.000 claims description 8
- PESVWIXUZNFVOB-UHFFFAOYSA-N 3-[(5-chloro-3-methyl-1-benzofuran-2-yl)sulfonyl]-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=C(C)C2=CC(Cl)=CC=C2O1 PESVWIXUZNFVOB-UHFFFAOYSA-N 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate Chemical compound [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 claims description 6
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 3
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000006085 pyrrolopyridyl group Chemical group 0.000 claims description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 claims description 3
- SGOLLMYWJZAGJJ-UHFFFAOYSA-N 3-[(5-chloro-3-methyl-1-benzofuran-2-yl)sulfanyl]-1h-pyridazin-6-one Chemical compound O1C2=CC=C(Cl)C=C2C(C)=C1SC1=CC=C(O)N=N1 SGOLLMYWJZAGJJ-UHFFFAOYSA-N 0.000 claims description 2
- CYXNLUKXQVTYHT-UHFFFAOYSA-N 3-[(5-chloro-3-methyl-1-benzofuran-2-yl)sulfanyl]-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1SC1=C(C)C2=CC(Cl)=CC=C2O1 CYXNLUKXQVTYHT-UHFFFAOYSA-N 0.000 claims description 2
- AMAQYLPFCRGWRB-UHFFFAOYSA-N 3-[(5-chloro-3-methyl-1-benzofuran-2-yl)sulfinyl]-1h-pyridazin-6-one Chemical compound O1C2=CC=C(Cl)C=C2C(C)=C1S(=O)C=1C=CC(=O)NN=1 AMAQYLPFCRGWRB-UHFFFAOYSA-N 0.000 claims description 2
- FFJIULXBRJZUKP-UHFFFAOYSA-N 5-chloro-3-methyl-1-benzofuran-2-thiol Chemical compound C1=C(Cl)C=C2C(C)=C(S)OC2=C1 FFJIULXBRJZUKP-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 12
- 125000005945 imidazopyridyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 95
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 80
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 57
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
- 239000000203 mixture Substances 0.000 description 48
- 235000019439 ethyl acetate Nutrition 0.000 description 47
- 238000006243 chemical reaction Methods 0.000 description 44
- 239000011541 reaction mixture Substances 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- 239000000706 filtrate Substances 0.000 description 30
- 239000002904 solvent Substances 0.000 description 30
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 26
- 239000003480 eluent Substances 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000010410 layer Substances 0.000 description 19
- 238000010898 silica gel chromatography Methods 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- 239000012043 crude product Substances 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 10
- IMOAIQFWGABIHK-UHFFFAOYSA-N 6-methoxypyridazine-3-sulfonyl fluoride Chemical compound COC1=CC=C(S(F)(=O)=O)N=N1 IMOAIQFWGABIHK-UHFFFAOYSA-N 0.000 description 10
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 9
- ULKNITLERDOAGN-UHFFFAOYSA-N 4-methoxy-1h-pyridazine-2-sulfonyl fluoride Chemical compound COC1=CN(S(F)(=O)=O)NC=C1 ULKNITLERDOAGN-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000007810 chemical reaction solvent Substances 0.000 description 8
- 229910052740 iodine Inorganic materials 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 239000011630 iodine Substances 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- DFLDLKPTMSEPFY-UHFFFAOYSA-N 2-(6-methoxypyridazin-3-yl)sulfonyl-1h-indole Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=CC2=CC=CC=C2N1 DFLDLKPTMSEPFY-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 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 6
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 150000003462 sulfoxides Chemical class 0.000 description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 5
- 239000002024 ethyl acetate extract Substances 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 150000002430 hydrocarbons Chemical class 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- YLXQGRSURQLXRU-UHFFFAOYSA-N 2-(6-methoxypyridazin-3-yl)sulfanyl-1h-indole Chemical compound N1=NC(OC)=CC=C1SC1=CC2=CC=CC=C2N1 YLXQGRSURQLXRU-UHFFFAOYSA-N 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- 239000004215 Carbon black (E152) Substances 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 150000001323 aldoses Chemical class 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- AVCJJKUQMCJKLH-UHFFFAOYSA-N (5-chloro-3-methyl-1-benzofuran-2-yl)methanol Chemical compound C1=C(Cl)C=C2C(C)=C(CO)OC2=C1 AVCJJKUQMCJKLH-UHFFFAOYSA-N 0.000 description 3
- QNVZJGDHVMKHAX-UHFFFAOYSA-N 1-(benzenesulfonyl)-2-(6-methoxypyridazin-3-yl)sulfonylindole Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=CC2=CC=CC=C2N1S(=O)(=O)C1=CC=CC=C1 QNVZJGDHVMKHAX-UHFFFAOYSA-N 0.000 description 3
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 3
- UELZRIBNQBXXFO-UHFFFAOYSA-N 2-(bromomethyl)-5-chloro-3-methyl-1-benzofuran Chemical compound C1=C(Cl)C=C2C(C)=C(CBr)OC2=C1 UELZRIBNQBXXFO-UHFFFAOYSA-N 0.000 description 3
- MRDCXUYQUSFQKF-UHFFFAOYSA-N 2-iodo-4-(trifluoromethyl)phenol Chemical compound OC1=CC=C(C(F)(F)F)C=C1I MRDCXUYQUSFQKF-UHFFFAOYSA-N 0.000 description 3
- GJAKTRLFNMJPDX-UHFFFAOYSA-N 3-(6-methoxypyridazin-3-yl)sulfonyl-1h-indole Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=CNC2=CC=CC=C12 GJAKTRLFNMJPDX-UHFFFAOYSA-N 0.000 description 3
- WUIBBMKVRCKPFM-UHFFFAOYSA-N 3-[(5-chloro-3-ethyl-1-benzofuran-2-yl)sulfonyl]-6-methoxypyridazine Chemical compound O1C2=CC=C(Cl)C=C2C(CC)=C1S(=O)(=O)C1=CC=C(OC)N=N1 WUIBBMKVRCKPFM-UHFFFAOYSA-N 0.000 description 3
- QFGVMDQFNSYTJG-UHFFFAOYSA-N 3-[(5-fluoro-3-methyl-1-benzofuran-2-yl)sulfonyl]-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=C(C)C2=CC(F)=CC=C2O1 QFGVMDQFNSYTJG-UHFFFAOYSA-N 0.000 description 3
- WKYDLYLCLLRDNF-UHFFFAOYSA-N 3-chloro-2-(6-methoxypyridazin-3-yl)sulfanyl-1h-indole Chemical compound N1=NC(OC)=CC=C1SC1=C(Cl)C2=CC=CC=C2N1 WKYDLYLCLLRDNF-UHFFFAOYSA-N 0.000 description 3
- YRAUAJNDSLLHKM-UHFFFAOYSA-N 3-chloro-6-phenylmethoxypyridazine Chemical compound N1=NC(Cl)=CC=C1OCC1=CC=CC=C1 YRAUAJNDSLLHKM-UHFFFAOYSA-N 0.000 description 3
- NWUYAYVDHURYQU-UHFFFAOYSA-N 3-methoxy-1h-pyridazine-6-thione Chemical compound COC1=CC=C(S)N=N1 NWUYAYVDHURYQU-UHFFFAOYSA-N 0.000 description 3
- UPCDGJJRRRLDNG-UHFFFAOYSA-N 3-methoxy-6-[[3-methyl-5-(trifluoromethyl)-1-benzofuran-2-yl]sulfonyl]pyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=C(C)C2=CC(C(F)(F)F)=CC=C2O1 UPCDGJJRRRLDNG-UHFFFAOYSA-N 0.000 description 3
- JEQNNAWQKPMCIR-UHFFFAOYSA-N 3-methyl-5-(trifluoromethyl)-1-benzofuran Chemical compound C1=C(C(F)(F)F)C=C2C(C)=COC2=C1 JEQNNAWQKPMCIR-UHFFFAOYSA-N 0.000 description 3
- JKPLMQJLGBBFLO-UHFFFAOYSA-N 4-chloro-2-iodophenol Chemical compound OC1=CC=C(Cl)C=C1I JKPLMQJLGBBFLO-UHFFFAOYSA-N 0.000 description 3
- UUAVJCDYOHIIQW-UHFFFAOYSA-N 4-sulfonylpyridazin-3-one Chemical compound O=C1N=NC=CC1=S(=O)=O UUAVJCDYOHIIQW-UHFFFAOYSA-N 0.000 description 3
- CSPBUYJDUCASLV-UHFFFAOYSA-N 5-chloro-3-ethyl-1-benzofuran Chemical compound C1=C(Cl)C=C2C(CC)=COC2=C1 CSPBUYJDUCASLV-UHFFFAOYSA-N 0.000 description 3
- XVZBANRRDRILGR-UHFFFAOYSA-N 5-chloro-3-methyl-1-benzofuran-2-carbaldehyde Chemical compound C1=C(Cl)C=C2C(C)=C(C=O)OC2=C1 XVZBANRRDRILGR-UHFFFAOYSA-N 0.000 description 3
- LZVAHYZQDSUVNN-UHFFFAOYSA-N 5-fluoro-3-methyl-1-benzofuran Chemical compound C1=C(F)C=C2C(C)=COC2=C1 LZVAHYZQDSUVNN-UHFFFAOYSA-N 0.000 description 3
- LBBABXHLFFJHLZ-UHFFFAOYSA-N 6-phenylmethoxypyridazine-3-sulfonyl fluoride Chemical compound N1=NC(S(=O)(=O)F)=CC=C1OCC1=CC=CC=C1 LBBABXHLFFJHLZ-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 102000004316 Oxidoreductases Human genes 0.000 description 3
- 108090000854 Oxidoreductases Proteins 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 239000003288 aldose reductase inhibitor Substances 0.000 description 3
- 150000001342 alkaline earth metals Chemical class 0.000 description 3
- 150000004703 alkoxides Chemical class 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- USBQRZMRUABNHR-UHFFFAOYSA-N but-2-enoxybenzene Chemical compound CC=CCOC1=CC=CC=C1 USBQRZMRUABNHR-UHFFFAOYSA-N 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000011017 operating method Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
- UCZHXZYWHUIRNL-UHFFFAOYSA-N 1-(6-methoxypyridazin-3-yl)sulfonyl-3,4,4a,5-tetrahydro-2h-quinoline Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)N1C2=CC=CCC2CCC1 UCZHXZYWHUIRNL-UHFFFAOYSA-N 0.000 description 2
- MGKPCLNUSDGXGT-UHFFFAOYSA-N 1-benzofuran-3-one Chemical compound C1=CC=C2C(=O)COC2=C1 MGKPCLNUSDGXGT-UHFFFAOYSA-N 0.000 description 2
- OMEVSMGQSQDQKM-UHFFFAOYSA-N 1-benzyl-5-[(6-methoxy-1,2-dihydropyridazin-3-yl)sulfonyl]indole Chemical compound N1NC(OC)=CC=C1S(=O)(=O)C1=CC=C(N(CC=2C=CC=CC=2)C=C2)C2=C1 OMEVSMGQSQDQKM-UHFFFAOYSA-N 0.000 description 2
- NNKOXOJYMOLKIP-UHFFFAOYSA-N 2-(4-fluorophenyl)-1-benzofuran Chemical compound C1=CC(F)=CC=C1C1=CC2=CC=CC=C2O1 NNKOXOJYMOLKIP-UHFFFAOYSA-N 0.000 description 2
- VYDAITDQWPUKNV-UHFFFAOYSA-N 2-(6-methoxypyridazin-3-yl)sulfonyl-1-benzofuran-3-ol Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=C(O)C2=CC=CC=C2O1 VYDAITDQWPUKNV-UHFFFAOYSA-N 0.000 description 2
- PNJLQQVSKCBNQC-UHFFFAOYSA-N 3-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonyl]-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=C(C)C2=CC(Cl)=CC=C2S1 PNJLQQVSKCBNQC-UHFFFAOYSA-N 0.000 description 2
- CEYSQVNFVSJMFB-UHFFFAOYSA-N 3-[(5-chloro-3-propan-2-yl-1-benzofuran-2-yl)sulfonyl]-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=C(C(C)C)C2=CC(Cl)=CC=C2O1 CEYSQVNFVSJMFB-UHFFFAOYSA-N 0.000 description 2
- KPKLHUKFRQLEFY-UHFFFAOYSA-N 3-chloro-2-(6-methoxypyridazin-3-yl)sulfonyl-1h-indole Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=C(Cl)C2=CC=CC=C2N1 KPKLHUKFRQLEFY-UHFFFAOYSA-N 0.000 description 2
- VFSVOYXYXXWLIJ-UHFFFAOYSA-N 3-methoxy-6-[(3-methyl-1-benzofuran-2-yl)sulfonyl]pyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=C(C)C2=CC=CC=C2O1 VFSVOYXYXXWLIJ-UHFFFAOYSA-N 0.000 description 2
- JGNBBXNQIPTAJD-UHFFFAOYSA-N 3-methoxy-6-pyrrol-1-ylsulfonylpyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)N1C=CC=C1 JGNBBXNQIPTAJD-UHFFFAOYSA-N 0.000 description 2
- GRKMDMKTAFRGLA-UHFFFAOYSA-N 3-phenylmethoxy-1h-pyridazine-6-thione Chemical compound N1=NC(S)=CC=C1OCC1=CC=CC=C1 GRKMDMKTAFRGLA-UHFFFAOYSA-N 0.000 description 2
- BAYGVMXZJBFEMB-UHFFFAOYSA-N 4-(trifluoromethyl)phenol Chemical compound OC1=CC=C(C(F)(F)F)C=C1 BAYGVMXZJBFEMB-UHFFFAOYSA-N 0.000 description 2
- UDTLANWPHSQSCO-UHFFFAOYSA-N 5-chloro-2-methyl-1-benzofuran Chemical compound ClC1=CC=C2OC(C)=CC2=C1 UDTLANWPHSQSCO-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 102000016912 Aldehyde Reductase Human genes 0.000 description 2
- 108010053754 Aldehyde reductase Proteins 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 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 2
- 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 2
- 208000002249 Diabetes Complications Diseases 0.000 description 2
- 206010012655 Diabetic complications Diseases 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 239000004280 Sodium formate Substances 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- ICXXXLGATNSZAV-UHFFFAOYSA-N butylazanium;chloride Chemical compound [Cl-].CCCC[NH3+] ICXXXLGATNSZAV-UHFFFAOYSA-N 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000000451 chemical ionisation Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 238000005227 gel permeation chromatography Methods 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 150000004965 peroxy acids Chemical class 0.000 description 2
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 2
- 235000019254 sodium formate Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
- AVMHMVJVHYGDOO-NSCUHMNNSA-N (e)-1-bromobut-2-ene Chemical compound C\C=C\CBr AVMHMVJVHYGDOO-NSCUHMNNSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- KOFFXZYMDLWRHX-UHFFFAOYSA-N 1-(5-fluoro-2-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC(F)=CC=C1O KOFFXZYMDLWRHX-UHFFFAOYSA-N 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N 1-Heptene Chemical group CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- AQXJFUYUNHLBGU-UHFFFAOYSA-N 1-benzyl-5-bromoindole Chemical compound C1=CC2=CC(Br)=CC=C2N1CC1=CC=CC=C1 AQXJFUYUNHLBGU-UHFFFAOYSA-N 0.000 description 1
- ZXJBBXNNCHLZHL-UHFFFAOYSA-N 2-[(6-methoxy-1,2-dihydropyridazin-3-yl)sulfonyl]-1h-indole Chemical compound N1NC(OC)=CC=C1S(=O)(=O)C1=CC2=CC=CC=C2N1 ZXJBBXNNCHLZHL-UHFFFAOYSA-N 0.000 description 1
- ZIJKEQKHNVTLAZ-UHFFFAOYSA-N 2-bromo-3-methyl-1-benzofuran Chemical compound C1=CC=C2C(C)=C(Br)OC2=C1 ZIJKEQKHNVTLAZ-UHFFFAOYSA-N 0.000 description 1
- LIKPSSVUULPRAC-UHFFFAOYSA-N 2-chloro-6-methoxy-1h-pyridazine Chemical compound COC1=CC=CN(Cl)N1 LIKPSSVUULPRAC-UHFFFAOYSA-N 0.000 description 1
- FVRYCPZDHKLBNR-UHFFFAOYSA-N 2-mercaptoindole Chemical compound C1=CC=C2NC(S)=CC2=C1 FVRYCPZDHKLBNR-UHFFFAOYSA-N 0.000 description 1
- XRRHYCCPDQQNBR-UHFFFAOYSA-N 2-methyl-5-(trifluoromethyl)-1-benzofuran Chemical compound FC(F)(F)C1=CC=C2OC(C)=CC2=C1 XRRHYCCPDQQNBR-UHFFFAOYSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- GUSWJGOYDXFJSI-UHFFFAOYSA-N 3,6-dichloropyridazine Chemical compound ClC1=CC=C(Cl)N=N1 GUSWJGOYDXFJSI-UHFFFAOYSA-N 0.000 description 1
- MKNRWYQTAIUZIG-UHFFFAOYSA-N 3-chloro-2-[(6-methoxy-1,2-dihydropyridazin-3-yl)sulfonyl]-1h-indole Chemical compound N1NC(OC)=CC=C1S(=O)(=O)C1=C(Cl)C2=CC=CC=C2N1 MKNRWYQTAIUZIG-UHFFFAOYSA-N 0.000 description 1
- XBJLKXOOHLLTPG-UHFFFAOYSA-N 3-chloro-6-methoxypyridazine Chemical compound COC1=CC=C(Cl)N=N1 XBJLKXOOHLLTPG-UHFFFAOYSA-N 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- GBSSYXMLLXIOCV-UHFFFAOYSA-N 5-chloro-3-methyl-1-benzofuran Chemical compound C1=C(Cl)C=C2C(C)=COC2=C1 GBSSYXMLLXIOCV-UHFFFAOYSA-N 0.000 description 1
- UWDQVEPXORTQFO-UHFFFAOYSA-N 5-chloro-3-methyl-1-benzothiophene Chemical compound C1=C(Cl)C=C2C(C)=CSC2=C1 UWDQVEPXORTQFO-UHFFFAOYSA-N 0.000 description 1
- HBODQAPNDVOAIZ-UHFFFAOYSA-N 5-chloro-3-propan-2-yl-1-benzofuran Chemical compound C1=C(Cl)C=C2C(C(C)C)=COC2=C1 HBODQAPNDVOAIZ-UHFFFAOYSA-N 0.000 description 1
- RFCNHVZVMVXJMJ-UHFFFAOYSA-N 5-methoxy-2-sulfanyl-1h-pyridazine Chemical compound COC1=CNN(S)C=C1 RFCNHVZVMVXJMJ-UHFFFAOYSA-N 0.000 description 1
- HPCAKFQJCXWAAX-UHFFFAOYSA-N 6-sulfonyl-1h-pyridazine Chemical compound O=S(=O)=C1C=CC=NN1 HPCAKFQJCXWAAX-UHFFFAOYSA-N 0.000 description 1
- DYHGFTMEUMYPOC-UHFFFAOYSA-N 8-(3-nitrophenyl)-6-(pyridin-4-ylmethyl)pyrido[2,3-d]pyridazin-5-one Chemical compound [O-][N+](=O)C1=CC=CC(C=2C3=NC=CC=C3C(=O)N(CC=3C=CN=CC=3)N=2)=C1 DYHGFTMEUMYPOC-UHFFFAOYSA-N 0.000 description 1
- 229940118148 Aldose reductase inhibitor Drugs 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 208000032781 Diabetic cardiomyopathy Diseases 0.000 description 1
- 206010063547 Diabetic macroangiopathy Diseases 0.000 description 1
- 206010054044 Diabetic microangiopathy Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 125000000746 allylic group Chemical group 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 201000009101 diabetic angiopathy Diseases 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Chemical group 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- FBPFZTCFMRRESA-GUCUJZIJSA-N galactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-GUCUJZIJSA-N 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000004806 hydroxypyridines Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000005453 ketone based solvent Substances 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
- BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- GXHMMDRXHUIUMN-UHFFFAOYSA-N methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O GXHMMDRXHUIUMN-UHFFFAOYSA-N 0.000 description 1
- LOTBYPQQWICYBB-UHFFFAOYSA-N methyl n-hexyl-n-[2-(hexylamino)ethyl]carbamate Chemical group CCCCCCNCCN(C(=O)OC)CCCCCC LOTBYPQQWICYBB-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- HVZWVEKIQMJYIK-UHFFFAOYSA-N nitryl chloride Chemical group [O-][N+](Cl)=O HVZWVEKIQMJYIK-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Chemical group 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- PWSBNTOBQBTNEJ-UHFFFAOYSA-N thieno[2,3-b]pyridine Chemical compound C1=C[CH]C2=C=CSC2=N1 PWSBNTOBQBTNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
-
- 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
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans 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 carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28005101P | 2001-03-30 | 2001-03-30 | |
| US280051P | 2001-03-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2274369T3 true ES2274369T3 (es) | 2007-05-16 |
Family
ID=23071435
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES04023149T Expired - Lifetime ES2274369T3 (es) | 2001-03-30 | 2002-01-31 | Intermedios utiles para la sintesis de piridazinonas inhibidoras de aldosa reductasa. |
| ES02716247T Expired - Lifetime ES2231681T3 (es) | 2001-03-30 | 2002-01-31 | Inhibidores de piridazinona de la aldosa reductasa. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02716247T Expired - Lifetime ES2231681T3 (es) | 2001-03-30 | 2002-01-31 | Inhibidores de piridazinona de la aldosa reductasa. |
Country Status (43)
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU714980B2 (en) | 1996-07-24 | 2000-01-13 | Warner-Lambert Company Llc | Isobutylgaba and its derivatives for the treatment of pain |
| EP1236720B1 (en) * | 2001-02-28 | 2005-06-15 | Pfizer Products Inc. | Sulfonyl pyridazinone compounds useful as aldose reductase inhibitors |
| EE200300470A (et) * | 2001-03-30 | 2004-02-16 | Pfizer Products Inc. | Aldoosreduktaasi püridasinooninhibiitorid |
| AU761191B2 (en) * | 2001-05-24 | 2003-05-29 | Pfizer Products Inc. | Therapies for tissue damage resulting from ischemia |
| IL162594A0 (en) * | 2002-01-09 | 2005-11-20 | Pfizer Prod Inc | Process and intermediates for pyridazinone antidiabetic agents |
| US20040092522A1 (en) * | 2002-08-15 | 2004-05-13 | Field Mark John | Synergistic combinations |
| US7419981B2 (en) * | 2002-08-15 | 2008-09-02 | Pfizer Inc. | Synergistic combinations of an alpha-2-delta ligand and a cGMP phosphodieterse 5 inhibitor |
| US6872833B2 (en) * | 2003-04-14 | 2005-03-29 | Hoffmann-La Roche Inc. | Adenosine receptor ligands |
| US8017634B2 (en) | 2003-12-29 | 2011-09-13 | President And Fellows Of Harvard College | Compositions for treating obesity and insulin resistance disorders |
| US7262318B2 (en) * | 2004-03-10 | 2007-08-28 | Pfizer, Inc. | Substituted heteroaryl- and phenylsulfamoyl compounds |
| AR049384A1 (es) | 2004-05-24 | 2006-07-26 | Glaxo Group Ltd | Derivados de purina |
| US8226977B2 (en) | 2004-06-04 | 2012-07-24 | Teva Pharmaceutical Industries Ltd. | Pharmaceutical composition containing irbesartan |
| US20050288340A1 (en) * | 2004-06-29 | 2005-12-29 | Pfizer Inc | Substituted heteroaryl- and phenylsulfamoyl compounds |
| EP1769088A2 (en) * | 2004-06-30 | 2007-04-04 | Whitehead Institute For Biomedical Research | Novel methods for high-throughput genome-wide location analysis |
| GB0514809D0 (en) | 2005-07-19 | 2005-08-24 | Glaxo Group Ltd | Compounds |
| US7741317B2 (en) | 2005-10-21 | 2010-06-22 | Bristol-Myers Squibb Company | LXR modulators |
| US7888376B2 (en) | 2005-11-23 | 2011-02-15 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
| EP1973876A2 (en) * | 2006-01-13 | 2008-10-01 | Wyeth | Sulfonyl substituted 1h-indoles as ligands for the 5-hydroxytryptamine receptors |
| RS52307B (sr) * | 2006-06-27 | 2012-12-31 | Takeda Pharmaceutical Company Limited | Kondenzovana ciklična jedinjenja |
| ATE547394T1 (de) | 2006-12-01 | 2012-03-15 | Bristol Myers Squibb Co | N-((3-benzyl)-2,2-(bis-phenyl)-propan-1- aminderivate als cetp-hemmer für die behandlung von atherosklerose und herz-kreislauf- erkrankungen |
| US8173645B2 (en) * | 2007-03-21 | 2012-05-08 | Takeda San Diego, Inc. | Glucokinase activators |
| EP2116618A1 (en) | 2008-05-09 | 2009-11-11 | Agency for Science, Technology And Research | Diagnosis and treatment of Kawasaki disease |
| CA2783699C (en) | 2009-12-08 | 2019-01-15 | Case Western Reserve University | Primary amine compounds for treating ocular disorders |
| 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 |
| EP2763673B1 (en) * | 2011-09-15 | 2018-08-01 | Taipei Medical University | Use of indolyl hydroxamates for treating heart failure or neuronal injury |
| US9339542B2 (en) * | 2013-04-16 | 2016-05-17 | John L Couvaras | Hypertension reducing composition |
| AU2014255381A1 (en) | 2013-04-17 | 2015-10-08 | Pfizer Inc. | N-piperidin-3-ylbenzamide derivatives for treating cardiovascular diseases |
| CN103739547B (zh) * | 2014-01-03 | 2015-09-02 | 沈阳药科大学 | 2-[6-甲氧基-3-(2,3-二氯苯基)甲基-4-氧代-1,4-二氢-1(4h)-喹啉基]乙酸的合成方法 |
| WO2016055901A1 (en) | 2014-10-08 | 2016-04-14 | Pfizer Inc. | Substituted amide compounds |
| AU2016248080A1 (en) * | 2015-04-14 | 2017-11-02 | Board Of Regents Of The University Of Texas System | Compositions and methods of modulating short-chain dehydrogenase activity |
| WO2017168174A1 (en) | 2016-04-02 | 2017-10-05 | N4 Pharma Uk Limited | New pharmaceutical forms of sildenafil |
| EP3352754B1 (en) | 2016-06-21 | 2020-09-02 | The Trustees of Columbia University in the City of New York | Aldose reductase inhibitors and methods of use thereof |
| WO2018002673A1 (en) | 2016-07-01 | 2018-01-04 | N4 Pharma Uk Limited | Novel formulations of angiotensin ii receptor antagonists |
| WO2018058109A1 (en) * | 2016-09-26 | 2018-03-29 | Nusirt Sciences, Inc. | Compositions and methods for treating metabolic disorders |
| JP7595413B2 (ja) | 2016-11-30 | 2024-12-06 | ケース ウエスタン リザーブ ユニバーシティ | １５－ｐｇｄｈ阻害剤とコルチコステロイドおよび／またはｔｎｆ阻害剤との組み合わせならびにその使用 |
| EP3576737A4 (en) | 2017-02-06 | 2021-04-21 | Case Western Reserve University | COMPOSITIONS AND METHODS OF MODULATING THE ACTIVITY OF SHORT CHAIN DEHYDROGENASE |
| IL272246B1 (en) | 2017-07-28 | 2025-09-01 | Applied Therapeutics Inc | Derivatives of 2-(4-oxo/thioketone/azo-3-((substituted)benzo[d]thiazol-2-yl)methyl)- 3,4-dihydrothieno[3,4-d]pyridazin-1-yl)acetic acid for use as aldose reductase inhibitors in treating galactosemia or preventing complications associated with galactosemia |
| EP3883577A4 (en) | 2018-11-21 | 2022-06-15 | Case Western Reserve University | COMPOSITIONS AND METHODS FOR MODULATION OF SHORT CHAIN DEHYDROGENASE ACTIVITY |
| DK3911648T3 (da) | 2019-01-18 | 2025-01-13 | Astrazeneca Ab | 6'-[[(1s,3s)-3-[[5-(difluormethoxy)-2-pyrimidinyl]amino]cyclopentyl]amino][1(2h),3'-bipyridin]-2-on som pcsk9-hæmmer og fremgangsmåder til anvendelse deraf |
| BR112021021939A2 (pt) | 2019-05-07 | 2022-02-22 | Ucl Business Ltd | Tratamento e detecção de neuropatias herdadas e distúrbios associados |
| SG11202113129UA (en) | 2019-05-31 | 2021-12-30 | Ikena Oncology Inc | Tead inhibitors and uses thereof |
| SG11202113154YA (en) | 2019-05-31 | 2021-12-30 | Ikena Oncology Inc | Tead inhibitors and uses thereof |
| WO2022120353A1 (en) * | 2020-12-02 | 2022-06-09 | Ikena Oncology, Inc. | Tead inhibitors and uses thereof |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE47592B1 (en) | 1977-12-29 | 1984-05-02 | Ici Ltd | Enzyme inhibitory phthalazin-4-ylacetic acid derivatives, pharmaceutical compositions thereof,and process for their manufacture |
| US4939140A (en) | 1985-11-07 | 1990-07-03 | Pfizer Inc. | Heterocyclic oxophthalazinyl acetic acids |
| US4996204A (en) | 1989-05-11 | 1991-02-26 | Pfizer Inc. | Pyrido[2,3-d]pyridazinones as aldose reductase inhibitors |
| FR2647676A1 (fr) | 1989-06-05 | 1990-12-07 | Union Pharma Scient Appl | Nouveaux derives de pyridazinone, leurs procedes de preparation, medicaments les contenant, utiles notamment comme inhibiteurs de l'aldose reductase |
| WO1992009594A1 (fr) * | 1990-11-30 | 1992-06-11 | Tsumura & Co. | Derive de benzopyrone et inhibiteur de reductase d'aldose contenant ce derive en tant qu'ingredient actif |
| CZ387092A3 (en) | 1991-03-28 | 1994-02-16 | Pfizer | Pyridazinoacetic acids, their derivatives, process of their preparation and use |
| US5834466A (en) | 1994-12-22 | 1998-11-10 | The Regents Of The University Of California | Method for protecting of heart by limiting metabolic and ionic abnormalities developed during ischemia, following ischemia or resulting from ischemia |
| TW438587B (en) | 1995-06-20 | 2001-06-07 | Takeda Chemical Industries Ltd | A pharmaceutical composition for prophylaxis and treatment of diabetes |
| WO1999015523A1 (en) * | 1997-09-24 | 1999-04-01 | Orion Corporation | Bisethers of 1-oxa, aza and thianaphthalen-2-ones as phospholamban inhibitors |
| FR2822827B1 (fr) * | 2001-03-28 | 2003-05-16 | Sanofi Synthelabo | Nouveaux derives de n-(arylsulfonyl) beta-aminoacides comportant un groupe aminomethyle substitue, leur procede de preparation et les compositions pharmaceutiques en contenant |
| EE200300470A (et) * | 2001-03-30 | 2004-02-16 | Pfizer Products Inc. | Aldoosreduktaasi püridasinooninhibiitorid |
| AU2002236131B2 (en) * | 2001-04-30 | 2005-04-14 | Pfizer Products Inc. | Combinations of aldose reductase inhibitors and cyclooxygenase-2 inhibitors |
| IL162594A0 (en) * | 2002-01-09 | 2005-11-20 | Pfizer Prod Inc | Process and intermediates for pyridazinone antidiabetic agents |
-
2002
- 2002-01-31 EE EEP200300470A patent/EE200300470A/xx unknown
- 2002-01-31 EP EP02716247A patent/EP1373259B1/en not_active Expired - Lifetime
- 2002-01-31 PT PT04023149T patent/PT1491540E/pt unknown
- 2002-01-31 ES ES04023149T patent/ES2274369T3/es not_active Expired - Lifetime
- 2002-01-31 EP EP04023149A patent/EP1491540B1/en not_active Expired - Lifetime
- 2002-01-31 DE DE60217930T patent/DE60217930T2/de not_active Expired - Fee Related
- 2002-01-31 HU HU0303644A patent/HUP0303644A3/hu unknown
- 2002-01-31 YU YU71403A patent/YU71403A/sh unknown
- 2002-01-31 SI SI200230071T patent/SI1373259T1/xx unknown
- 2002-01-31 MX MXPA03008850A patent/MXPA03008850A/es active IP Right Grant
- 2002-01-31 JP JP2002577823A patent/JP2004528319A/ja active Pending
- 2002-01-31 DE DE60216823T patent/DE60216823T2/de not_active Expired - Fee Related
- 2002-01-31 BR BR0208571-2A patent/BR0208571A/pt not_active IP Right Cessation
- 2002-01-31 UA UA2003098846A patent/UA73236C2/uk unknown
- 2002-01-31 NZ NZ528406A patent/NZ528406A/en unknown
- 2002-01-31 AT AT04023149T patent/ATE348100T1/de not_active IP Right Cessation
- 2002-01-31 PT PT02716247T patent/PT1373259E/pt unknown
- 2002-01-31 GE GE5314A patent/GEP20053675B/en unknown
- 2002-01-31 AU AU2002226634A patent/AU2002226634B2/en not_active Ceased
- 2002-01-31 EP EP04023150A patent/EP1491541B1/en not_active Expired - Lifetime
- 2002-01-31 ES ES02716247T patent/ES2231681T3/es not_active Expired - Lifetime
- 2002-01-31 CN CNB028076001A patent/CN1215067C/zh not_active Expired - Fee Related
- 2002-01-31 DK DK04023149T patent/DK1491540T3/da active
- 2002-01-31 KR KR1020037012753A patent/KR100586138B1/ko not_active Expired - Fee Related
- 2002-01-31 EA EA200300673A patent/EA006023B1/ru not_active IP Right Cessation
- 2002-01-31 IL IL15646202A patent/IL156462A0/xx unknown
- 2002-01-31 DK DK02716247T patent/DK1373259T3/da active
- 2002-01-31 HR HR20030752A patent/HRP20030752A2/hr not_active Application Discontinuation
- 2002-01-31 AT AT04023150T patent/ATE352551T1/de not_active IP Right Cessation
- 2002-01-31 PL PL02365294A patent/PL365294A1/xx not_active Application Discontinuation
- 2002-01-31 WO PCT/IB2002/000320 patent/WO2002079198A1/en not_active Ceased
- 2002-01-31 DE DE60202452T patent/DE60202452C5/de not_active Expired - Fee Related
- 2002-01-31 CA CA002442476A patent/CA2442476A1/en not_active Abandoned
- 2002-01-31 OA OA1200300222A patent/OA12453A/en unknown
- 2002-01-31 AT AT02716247T patent/ATE286049T1/de active
- 2002-01-31 SK SK1185-2003A patent/SK11852003A3/sk unknown
- 2002-03-21 US US10/104,664 patent/US6579879B2/en not_active Expired - Fee Related
- 2002-03-22 PA PA20028541801A patent/PA8541801A1/es unknown
- 2002-03-27 AR ARP020101134A patent/AR035798A1/es unknown
- 2002-03-27 UY UY27237A patent/UY27237A1/es not_active Application Discontinuation
- 2002-03-27 PE PE2002000246A patent/PE20030007A1/es not_active Application Discontinuation
- 2002-03-27 MY MYPI20021093A patent/MY134304A/en unknown
- 2002-03-28 AP APAP/P/2002/002461A patent/AP2002002461A0/en unknown
- 2002-03-29 TN TNTNSN02037A patent/TNSN02037A1/fr unknown
- 2002-03-29 TW TW091106386A patent/TWI245762B/zh not_active IP Right Cessation
- 2002-03-31 CZ CZ20032563A patent/CZ20032563A3/cs unknown
-
2003
- 2003-02-20 US US10/370,895 patent/US6849629B2/en not_active Expired - Fee Related
- 2003-06-16 IS IS6845A patent/IS2205B/is unknown
- 2003-06-17 ZA ZA200304671A patent/ZA200304671B/en unknown
- 2003-06-25 EC EC2003004671A patent/ECSP034671A/es unknown
- 2003-09-17 MA MA27314A patent/MA27003A1/fr unknown
- 2003-09-17 BG BG108179A patent/BG108179A/xx unknown
- 2003-09-29 NO NO20034345A patent/NO20034345D0/no unknown
-
2006
- 2006-01-23 IS IS8250A patent/IS8250A/is unknown
- 2006-01-23 IS IS8251A patent/IS8251A/is unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2274369T3 (es) | Intermedios utiles para la sintesis de piridazinonas inhibidoras de aldosa reductasa. | |
| KR102824574B1 (ko) | Pad 억제제로서의 헤테로사이클릭 화합물 | |
| ES2251867B1 (es) | Nuevos derivados de piridazin-3(2h)-ona. | |
| ES2262996T3 (es) | Deazapurinas y sus usos. | |
| ES2533241T3 (es) | Aminopirimidinas útiles como inhibidores de cinasas | |
| ES2231526T3 (es) | Ciclopentaindoles, composiciones que contienen dichos compuestos y procedimientos de tratamiento. | |
| ES2216631T3 (es) | Pirazolpiridinas. | |
| ES2527105T3 (es) | Derivados de piridina condensados como inhibidores de quinasas | |
| ES2208685T3 (es) | Inhibidores de indolizina spla2. | |
| EP3436459B1 (en) | Fused pentacyclic imidazole derivatives as modulators of tnf activity | |
| HRP960289A2 (en) | Aromatic compounds | |
| ES2344836T3 (es) | Indoles utiles en el tratamiento de enfermedades relacionadas con el receptor androgenico. | |
| WO2004093872A1 (en) | 3-oxo-1, 3-dihydro-indazole-2-carboxylic acid amide derivatives as phospholipase inhibitors | |
| WO1994010158A1 (fr) | Nouveaux derives de 1,2-benzisoxazole ou sel dudit derive, et agent de protection cerebrale contenant ce derive | |
| CN110461842A (zh) | 作为tnf活性调节剂的稠合五环咪唑衍生物 | |
| ES2231500T3 (es) | Derivados de difenilmetano. | |
| ES2380670T3 (es) | Inhibidores de MMP | |
| US10793578B2 (en) | Fused pentacyclic imidazole derivatives as modulators of TNF activity | |
| JP2020502129A (ja) | Ｎｒｆ２アクチベーターとしての３−オキソ−１，４−ジアゼピニル化合物 | |
| ES2219031T3 (es) | Nuevos benzoxazoles con actividad inhibidora de pde. | |
| WO2017075341A1 (en) | Fused imidazole derivatives as ido/tdo inhibitors | |
| ES2309822T3 (es) | Derivado de amida del acido pirrolopiridina-2-carboxilico util como inhibidor de la glucogeno-fosforilasa. | |
| ES2200829T3 (es) | Analogos opticamente puros de la campotecina. | |
| WO1998011103A1 (en) | New pharmaceutically active compounds | |
| JP2004529183A (ja) | 化合物 |