SK7332002A3 - Method of reducing tissue damage associated with ischemia - Google Patents
Method of reducing tissue damage associated with ischemia Download PDFInfo
- Publication number
- SK7332002A3 SK7332002A3 SK733-2002A SK7332002A SK7332002A3 SK 7332002 A3 SK7332002 A3 SK 7332002A3 SK 7332002 A SK7332002 A SK 7332002A SK 7332002 A3 SK7332002 A3 SK 7332002A3
- Authority
- SK
- Slovakia
- Prior art keywords
- pyridazin
- benzenesulfonyl
- group
- compound
- carbon atoms
- Prior art date
Links
- 208000028867 ischemia Diseases 0.000 title claims abstract description 15
- 230000000451 tissue damage Effects 0.000 title claims abstract description 6
- 231100000827 tissue damage Toxicity 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 title description 34
- 241000124008 Mammalia Species 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 155
- 125000004432 carbon atom Chemical group C* 0.000 claims description 39
- 239000000651 prodrug Substances 0.000 claims description 30
- 229940002612 prodrug Drugs 0.000 claims description 30
- 210000002216 heart Anatomy 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- -1 2,3-difluoro-benzenesulfonyl Chemical group 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- 210000001519 tissue Anatomy 0.000 claims description 21
- 239000000460 chlorine Chemical group 0.000 claims description 18
- 229910052801 chlorine Inorganic materials 0.000 claims description 18
- 125000001624 naphthyl group Chemical group 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 102000016912 Aldehyde Reductase Human genes 0.000 claims description 13
- 108010053754 Aldehyde reductase Proteins 0.000 claims description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- FAPYYQBGANAWEI-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)sulfonyl-1h-pyridazin-6-one Chemical class ClC1=CC(Cl)=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 FAPYYQBGANAWEI-UHFFFAOYSA-N 0.000 claims description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- JORLLGPOJPMFRS-UHFFFAOYSA-N 3-(3-chlorophenyl)sulfonyl-1h-pyridazin-6-one Chemical compound ClC1=CC=CC(S(=O)(=O)C2=NNC(=O)C=C2)=C1 JORLLGPOJPMFRS-UHFFFAOYSA-N 0.000 claims description 8
- HJXKXDILPXEWJY-UHFFFAOYSA-N 3-naphthalen-1-ylsulfonyl-1h-pyridazin-6-one Chemical class N1C(=O)C=CC(S(=O)(=O)C=2C3=CC=CC=C3C=CC=2)=N1 HJXKXDILPXEWJY-UHFFFAOYSA-N 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- YIGVCMPHSHVCQW-UHFFFAOYSA-N 3-(2,3-difluorophenyl)sulfonyl-1h-pyridazin-6-one Chemical class FC1=CC=CC(S(=O)(=O)C2=NNC(=O)C=C2)=C1F YIGVCMPHSHVCQW-UHFFFAOYSA-N 0.000 claims description 7
- ABHDLEMQXCSODP-UHFFFAOYSA-N 3-(2-bromo-4-fluorophenyl)sulfonyl-1h-pyridazin-6-one Chemical class BrC1=CC(F)=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 ABHDLEMQXCSODP-UHFFFAOYSA-N 0.000 claims description 7
- FTLDTGWMVVXYAM-UHFFFAOYSA-N 3-(2-chlorophenyl)sulfonyl-1h-pyridazin-6-one Chemical compound ClC1=CC=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 FTLDTGWMVVXYAM-UHFFFAOYSA-N 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 239000011737 fluorine Chemical group 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical group [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 7
- WSTJUPLIBBVJLM-UHFFFAOYSA-N 3-(2,3-dichlorophenyl)sulfonyl-1h-pyridazin-6-one Chemical compound ClC1=CC=CC(S(=O)(=O)C2=NNC(=O)C=C2)=C1Cl WSTJUPLIBBVJLM-UHFFFAOYSA-N 0.000 claims description 6
- QBQUUVFMUNTIDP-UHFFFAOYSA-N 3-(2,4-difluorophenyl)sulfonyl-1h-pyridazin-6-one Chemical class FC1=CC(F)=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 QBQUUVFMUNTIDP-UHFFFAOYSA-N 0.000 claims description 6
- TYTJJEITRZSQRD-UHFFFAOYSA-N 3-(2,5-dichlorophenyl)sulfonyl-1h-pyridazin-6-one Chemical class ClC1=CC=C(Cl)C(S(=O)(=O)C2=NNC(=O)C=C2)=C1 TYTJJEITRZSQRD-UHFFFAOYSA-N 0.000 claims description 6
- OTXVZGMQNJRLIN-UHFFFAOYSA-N 3-(2,6-dichlorophenyl)sulfonyl-1h-pyridazin-6-one Chemical class ClC1=CC=CC(Cl)=C1S(=O)(=O)C1=NNC(=O)C=C1 OTXVZGMQNJRLIN-UHFFFAOYSA-N 0.000 claims description 6
- AFMMZMYEGLGTBX-UHFFFAOYSA-N 3-(2-chloro-4-fluorophenyl)sulfonyl-1h-pyridazin-6-one Chemical class ClC1=CC(F)=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 AFMMZMYEGLGTBX-UHFFFAOYSA-N 0.000 claims description 6
- AEDNYZQZIZUZTP-UHFFFAOYSA-N 3-(2-fluorophenyl)sulfonyl-1h-pyridazin-6-one Chemical class FC1=CC=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 AEDNYZQZIZUZTP-UHFFFAOYSA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 210000005003 heart tissue Anatomy 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- MLRLSUWJTAHEKD-UHFFFAOYSA-N 3-(4-chlorophenyl)sulfonyl-1h-pyridazin-6-one Chemical class C1=CC(Cl)=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 MLRLSUWJTAHEKD-UHFFFAOYSA-N 0.000 claims description 4
- OVAVDZRNJWQJPL-UHFFFAOYSA-N 3-(4-fluorophenyl)sulfonyl-1h-pyridazin-6-one Chemical class C1=CC(F)=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 OVAVDZRNJWQJPL-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 210000003734 kidney Anatomy 0.000 claims description 4
- 210000001525 retina Anatomy 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- LOTBYPQQWICYBB-UHFFFAOYSA-N methyl n-hexyl-n-[2-(hexylamino)ethyl]carbamate Chemical compound CCCCCCNCCN(C(=O)OC)CCCCCC LOTBYPQQWICYBB-UHFFFAOYSA-N 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 230000000968 intestinal effect Effects 0.000 claims description 2
- 210000000936 intestine Anatomy 0.000 claims description 2
- 210000004185 liver Anatomy 0.000 claims description 2
- 210000000496 pancreas Anatomy 0.000 claims description 2
- 210000002027 skeletal muscle Anatomy 0.000 claims description 2
- 210000000952 spleen Anatomy 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 230000002265 prevention Effects 0.000 abstract description 4
- 238000002560 therapeutic procedure Methods 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
- 239000000203 mixture Substances 0.000 description 50
- 239000000243 solution Substances 0.000 description 37
- 238000006243 chemical reaction Methods 0.000 description 32
- 239000002904 solvent Substances 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000000047 product Substances 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- 239000011541 reaction mixture Substances 0.000 description 22
- 239000007787 solid Substances 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 238000009835 boiling Methods 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000002844 melting Methods 0.000 description 18
- 230000008018 melting Effects 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 239000010410 layer Substances 0.000 description 13
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 239000003288 aldose reductase inhibitor Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 229950006238 nadide Drugs 0.000 description 9
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 8
- 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 8
- 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 8
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
- 229910052783 alkali metal Inorganic materials 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 8
- 239000000600 sorbitol Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 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 7
- 239000002253 acid Substances 0.000 description 7
- 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 7
- 125000001309 chloro group Chemical group Cl* 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 230000000302 ischemic effect Effects 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 229930091371 Fructose Natural products 0.000 description 6
- 239000005715 Fructose Substances 0.000 description 6
- 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 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- PKDBCJSWQUOKDO-UHFFFAOYSA-M 2,3,5-triphenyltetrazolium chloride Chemical compound [Cl-].C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 PKDBCJSWQUOKDO-UHFFFAOYSA-M 0.000 description 4
- 229940118148 Aldose reductase inhibitor Drugs 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 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 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 230000005961 cardioprotection Effects 0.000 description 4
- 210000004351 coronary vessel Anatomy 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 239000002024 ethyl acetate extract Substances 0.000 description 4
- 150000008282 halocarbons Chemical class 0.000 description 4
- QANJXUAGWMIDJA-UHFFFAOYSA-N n-methyl-6-oxo-n-phenyl-1h-pyridazine-3-sulfonamide Chemical compound C1=CC(=O)NN=C1S(=O)(=O)N(C)C1=CC=CC=C1 QANJXUAGWMIDJA-UHFFFAOYSA-N 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- HMSZIGKFWDEQQU-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)sulfanyl-1h-pyridazin-6-one Chemical compound ClC1=CC(Cl)=CC=C1SC1=NNC(=O)C=C1 HMSZIGKFWDEQQU-UHFFFAOYSA-N 0.000 description 3
- SQXSQAMTEFWNFO-UHFFFAOYSA-N 3-(2-fluorophenyl)sulfonyl-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=CC=CC=C1F SQXSQAMTEFWNFO-UHFFFAOYSA-N 0.000 description 3
- SVFLJNRAWWEZEJ-UHFFFAOYSA-N 3-(3-chlorophenyl)sulfanyl-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1SC1=CC=CC(Cl)=C1 SVFLJNRAWWEZEJ-UHFFFAOYSA-N 0.000 description 3
- VGIQMJWDNYWNEV-UHFFFAOYSA-N 3-(3-chlorophenyl)sulfonyl-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=CC=CC(Cl)=C1 VGIQMJWDNYWNEV-UHFFFAOYSA-N 0.000 description 3
- AOSBVSOJGVLBCE-UHFFFAOYSA-N 3-(4-bromo-2-fluorophenyl)sulfonyl-1h-pyridazin-6-one Chemical compound FC1=CC(Br)=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 AOSBVSOJGVLBCE-UHFFFAOYSA-N 0.000 description 3
- FAIMMXDPWNZYOJ-UHFFFAOYSA-N 3-(4-phenylphenyl)sulfonyl-1h-pyridazin-6-one Chemical compound N1C(=O)C=CC(S(=O)(=O)C=2C=CC(=CC=2)C=2C=CC=CC=2)=N1 FAIMMXDPWNZYOJ-UHFFFAOYSA-N 0.000 description 3
- SBCIHAUEZVEELF-UHFFFAOYSA-N 3-[2-(4-chlorophenyl)-2-oxoethyl]sulfonyl-1h-pyridazin-6-one Chemical compound C1=CC(Cl)=CC=C1C(=O)CS(=O)(=O)C1=NNC(=O)C=C1 SBCIHAUEZVEELF-UHFFFAOYSA-N 0.000 description 3
- XBJLKXOOHLLTPG-UHFFFAOYSA-N 3-chloro-6-methoxypyridazine Chemical compound COC1=CC=C(Cl)N=N1 XBJLKXOOHLLTPG-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 241000282412 Homo Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 150000004703 alkoxides Chemical class 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- 239000012380 dealkylating agent Substances 0.000 description 3
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000034659 glycolysis Effects 0.000 description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 210000005240 left ventricle Anatomy 0.000 description 3
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 3
- 229910052753 mercury Inorganic materials 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
- GUSWJGOYDXFJSI-UHFFFAOYSA-N 3,6-dichloropyridazine Chemical compound ClC1=CC=C(Cl)N=N1 GUSWJGOYDXFJSI-UHFFFAOYSA-N 0.000 description 2
- ASZZHBXPMOVHCU-UHFFFAOYSA-N 3,9-diazaspiro[5.5]undecane-2,4-dione Chemical compound C1C(=O)NC(=O)CC11CCNCC1 ASZZHBXPMOVHCU-UHFFFAOYSA-N 0.000 description 2
- MLFKNCYUUMLHTD-UHFFFAOYSA-N 3-(2-bromophenyl)sulfonyl-1h-pyridazin-6-one Chemical compound BrC1=CC=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 MLFKNCYUUMLHTD-UHFFFAOYSA-N 0.000 description 2
- RIINLYDNHLFQOL-UHFFFAOYSA-N 3-(2-chloro-4-fluorophenyl)sulfonyl-6-methoxy-1-oxidopyridazin-1-ium Chemical compound ClC1=C(C=CC(=C1)F)S(=O)(=O)C=1N=[N+](C(=CC=1)OC)[O-] RIINLYDNHLFQOL-UHFFFAOYSA-N 0.000 description 2
- OYTBQPDDKDRHMJ-UHFFFAOYSA-N 3-(2-chlorophenyl)sulfonyl-6-methoxy-1-oxidopyridazin-1-ium Chemical compound ClC1=C(C=CC=C1)S(=O)(=O)C=1N=[N+](C(=CC=1)OC)[O-] OYTBQPDDKDRHMJ-UHFFFAOYSA-N 0.000 description 2
- IOKVRVLUPZCWEC-UHFFFAOYSA-N 3-(2-fluorophenyl)sulfanyl-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1SC1=CC=CC=C1F IOKVRVLUPZCWEC-UHFFFAOYSA-N 0.000 description 2
- ZONWJPVOPKFZOT-UHFFFAOYSA-N 3-(2-hydroxyphenyl)sulfonyl-1h-pyridazin-6-one Chemical compound OC1=CC=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 ZONWJPVOPKFZOT-UHFFFAOYSA-N 0.000 description 2
- QDLUZHBVOVEPQT-UHFFFAOYSA-N 3-(3,4-dichlorophenyl)sulfonyl-1h-pyridazin-6-one Chemical compound C1=C(Cl)C(Cl)=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 QDLUZHBVOVEPQT-UHFFFAOYSA-N 0.000 description 2
- HWLVTSGISYBNKC-UHFFFAOYSA-N 3-(3-bromophenyl)sulfonyl-1h-pyridazin-6-one Chemical compound BrC1=CC=CC(S(=O)(=O)C2=NNC(=O)C=C2)=C1 HWLVTSGISYBNKC-UHFFFAOYSA-N 0.000 description 2
- PSEZJPJCXYRNFR-UHFFFAOYSA-N 3-(4-bromo-2-fluorophenyl)sulfanyl-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1SC1=CC=C(Br)C=C1F PSEZJPJCXYRNFR-UHFFFAOYSA-N 0.000 description 2
- YQHOTFJDLFGOPK-UHFFFAOYSA-N 3-(4-bromo-2-fluorophenyl)sulfonyl-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=CC=C(Br)C=C1F YQHOTFJDLFGOPK-UHFFFAOYSA-N 0.000 description 2
- KLWAIVHFGCYFDO-UHFFFAOYSA-N 3-(4-methoxyphenyl)sulfonyl-1h-pyridazin-6-one Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 KLWAIVHFGCYFDO-UHFFFAOYSA-N 0.000 description 2
- LGSWVTSRHBLFNZ-UHFFFAOYSA-N 3-[3-(trifluoromethyl)phenyl]sulfonyl-1h-pyridazin-6-one Chemical compound FC(F)(F)C1=CC=CC(S(=O)(=O)C2=NNC(=O)C=C2)=C1 LGSWVTSRHBLFNZ-UHFFFAOYSA-N 0.000 description 2
- UJIMGLGZWPXNND-UHFFFAOYSA-N 3-[4-(trifluoromethyl)phenyl]sulfonyl-1h-pyridazin-6-one Chemical compound C1=CC(C(F)(F)F)=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 UJIMGLGZWPXNND-UHFFFAOYSA-N 0.000 description 2
- YRAUAJNDSLLHKM-UHFFFAOYSA-N 3-chloro-6-phenylmethoxypyridazine Chemical compound N1=NC(Cl)=CC=C1OCC1=CC=CC=C1 YRAUAJNDSLLHKM-UHFFFAOYSA-N 0.000 description 2
- NWUYAYVDHURYQU-UHFFFAOYSA-N 3-methoxy-1h-pyridazine-6-thione Chemical compound COC1=CC=C(S)N=N1 NWUYAYVDHURYQU-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
- SDUFOZCXUAUSJH-UHFFFAOYSA-N 6-methoxy-n-methyl-n-phenylpyridazine-3-sulfonamide Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)N(C)C1=CC=CC=C1 SDUFOZCXUAUSJH-UHFFFAOYSA-N 0.000 description 2
- 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 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 2
- 150000001242 acetic acid derivatives Chemical class 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 208000008784 apnea Diseases 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000000451 chemical ionisation Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- SHZIWNPUGXLXDT-UHFFFAOYSA-N ethyl hexanoate Chemical compound CCCCCC(=O)OCC SHZIWNPUGXLXDT-UHFFFAOYSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 239000006199 nebulizer Substances 0.000 description 2
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 150000004965 peroxy acids Chemical class 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 239000008057 potassium phosphate buffer Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 239000003379 purinergic P1 receptor agonist Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 1
- WLCYCEJSJRFSSQ-SCFUHWHPSA-N (2r,3r,4s,5r)-2-[2-(4-aminophenyl)ethyl]-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=CC(N)=CC=C1CC[C@]1(N2C3=NC=NC(N)=C3N=C2)[C@H](O)[C@H](O)[C@@H](CO)O1 WLCYCEJSJRFSSQ-SCFUHWHPSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
- COMPQGQRKOAAQI-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-(6-methoxypyridazin-3-yl)sulfanylethanone Chemical compound N1=NC(OC)=CC=C1SCC(=O)C1=CC=C(Cl)C=C1 COMPQGQRKOAAQI-UHFFFAOYSA-N 0.000 description 1
- RPGRGBUZKHZLBB-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-(6-methoxypyridazin-3-yl)sulfonylethanone Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)CC(=O)C1=CC=C(Cl)C=C1 RPGRGBUZKHZLBB-UHFFFAOYSA-N 0.000 description 1
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 1
- FGBVJFREPSJSNG-UHFFFAOYSA-N 2,4-dichlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1Cl FGBVJFREPSJSNG-UHFFFAOYSA-N 0.000 description 1
- YQIHGXFRQMFQPZ-UHFFFAOYSA-N 2,6-dichloro-1h-pyridazine Chemical compound ClN1NC(Cl)=CC=C1 YQIHGXFRQMFQPZ-UHFFFAOYSA-N 0.000 description 1
- PTTPXKJBFFKCEK-UHFFFAOYSA-N 2-Methyl-4-heptanone Chemical compound CC(C)CC(=O)CC(C)C PTTPXKJBFFKCEK-UHFFFAOYSA-N 0.000 description 1
- FLAYZKKEOIAALB-UHFFFAOYSA-N 2-bromo-1-(4-chlorophenyl)ethanone Chemical compound ClC1=CC=C(C(=O)CBr)C=C1 FLAYZKKEOIAALB-UHFFFAOYSA-N 0.000 description 1
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 1
- DUSNCFKVMGTTFK-UHFFFAOYSA-N 3,4-dichloro-n-methylaniline Chemical compound CNC1=CC=C(Cl)C(Cl)=C1 DUSNCFKVMGTTFK-UHFFFAOYSA-N 0.000 description 1
- JADVVTZXHQUFLS-UHFFFAOYSA-N 3,4-dichloropyridazine Chemical class ClC1=CC=NN=C1Cl JADVVTZXHQUFLS-UHFFFAOYSA-N 0.000 description 1
- KWTCIEHQOOENIF-UHFFFAOYSA-N 3-(2-chloro-4,6-difluorophenyl)sulfonyl-1h-pyridazin-6-one Chemical compound ClC1=CC(F)=CC(F)=C1S(=O)(=O)C1=NNC(=O)C=C1 KWTCIEHQOOENIF-UHFFFAOYSA-N 0.000 description 1
- OYWACMOXEJGSOH-UHFFFAOYSA-N 3-(2-chloro-4-fluorophenyl)sulfonyl-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=CC=C(F)C=C1Cl OYWACMOXEJGSOH-UHFFFAOYSA-N 0.000 description 1
- DZXIQIMPLWASQZ-UHFFFAOYSA-N 3-(2-chlorophenyl)sulfanyl-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1SC1=CC=CC=C1Cl DZXIQIMPLWASQZ-UHFFFAOYSA-N 0.000 description 1
- UTROKTGDEXINGT-UHFFFAOYSA-N 3-(2-chlorophenyl)sulfonyl-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=CC=CC=C1Cl UTROKTGDEXINGT-UHFFFAOYSA-N 0.000 description 1
- CGGRBPCBVJGYBF-UHFFFAOYSA-N 3-(2-methoxyphenyl)sulfonyl-1h-pyridazin-6-one Chemical compound COC1=CC=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 CGGRBPCBVJGYBF-UHFFFAOYSA-N 0.000 description 1
- PICCQCWBQAQOHS-UHFFFAOYSA-N 3-(2-phenylphenyl)sulfonyl-1h-pyridazin-6-one Chemical compound N1C(=O)C=CC(S(=O)(=O)C=2C(=CC=CC=2)C=2C=CC=CC=2)=N1 PICCQCWBQAQOHS-UHFFFAOYSA-N 0.000 description 1
- AONMKHSFCRKJFE-UHFFFAOYSA-N 3-(3-chloro-5-methylphenyl)sulfonyl-1h-pyridazin-6-one Chemical compound CC1=CC(Cl)=CC(S(=O)(=O)C2=NNC(=O)C=C2)=C1 AONMKHSFCRKJFE-UHFFFAOYSA-N 0.000 description 1
- VDQNIPJZZJXXHK-UHFFFAOYSA-N 3-(4-fluorophenyl)sulfanyl-1h-pyridazin-6-one Chemical compound C1=CC(F)=CC=C1SC1=NNC(=O)C=C1 VDQNIPJZZJXXHK-UHFFFAOYSA-N 0.000 description 1
- XOSZDFFWFSUHFO-UHFFFAOYSA-N 3-(4-fluorophenyl)sulfanyl-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1SC1=CC=C(F)C=C1 XOSZDFFWFSUHFO-UHFFFAOYSA-N 0.000 description 1
- MXDNDKAQPPQVKJ-UHFFFAOYSA-N 3-(4-fluorophenyl)sulfonyl-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=CC=C(F)C=C1 MXDNDKAQPPQVKJ-UHFFFAOYSA-N 0.000 description 1
- UJGXVIPGZVWFKT-UHFFFAOYSA-N 3-[2-(4-chlorophenyl)-2-hydroxyethyl]sulfonyl-1h-pyridazin-6-one Chemical compound C=1C=C(Cl)C=CC=1C(O)CS(=O)(=O)C=1C=CC(=O)NN=1 UJGXVIPGZVWFKT-UHFFFAOYSA-N 0.000 description 1
- LNGBUGBGXJHFOB-UHFFFAOYSA-N 3-[2-[4-(trifluoromethyl)phenyl]phenyl]sulfonyl-1h-pyridazin-6-one Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1S(=O)(=O)C1=NNC(=O)C=C1 LNGBUGBGXJHFOB-UHFFFAOYSA-N 0.000 description 1
- ABEAMJWANVQUNH-UHFFFAOYSA-N 3-[4-(4-fluorophenyl)phenyl]sulfonyl-1h-pyridazin-6-one Chemical compound C1=CC(F)=CC=C1C1=CC=C(S(=O)(=O)C2=NNC(=O)C=C2)C=C1 ABEAMJWANVQUNH-UHFFFAOYSA-N 0.000 description 1
- OHGYUDHKOAUOGF-UHFFFAOYSA-N 3-[4-[3,5-bis(trifluoromethyl)phenyl]phenyl]sulfonyl-1h-pyridazin-6-one Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C=2C=CC(=CC=2)S(=O)(=O)C2=NNC(=O)C=C2)=C1 OHGYUDHKOAUOGF-UHFFFAOYSA-N 0.000 description 1
- VMNQHFMDBDKSAV-UHFFFAOYSA-N 3-[4-[4-(trifluoromethyl)phenyl]phenyl]sulfonyl-1h-pyridazin-6-one Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=C(S(=O)(=O)C2=NNC(=O)C=C2)C=C1 VMNQHFMDBDKSAV-UHFFFAOYSA-N 0.000 description 1
- YICPBKWYZXFJNB-UHFFFAOYSA-N 3-chloro-1h-pyridazin-6-one Chemical compound OC1=CC=C(Cl)N=N1 YICPBKWYZXFJNB-UHFFFAOYSA-N 0.000 description 1
- CQJDYPZUDYXHLM-UHFFFAOYSA-N 3-chlorobenzenethiol Chemical compound SC1=CC=CC(Cl)=C1 CQJDYPZUDYXHLM-UHFFFAOYSA-N 0.000 description 1
- VKUPNZYEFAJSRQ-UHFFFAOYSA-N 3-methoxy-6-(4-phenylphenyl)sulfonylpyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=CC=C(C=2C=CC=CC=2)C=C1 VKUPNZYEFAJSRQ-UHFFFAOYSA-N 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
- OKIHXNKYYGUVTE-UHFFFAOYSA-N 4-Fluorothiophenol Chemical compound FC1=CC=C(S)C=C1 OKIHXNKYYGUVTE-UHFFFAOYSA-N 0.000 description 1
- KENIDQSHNHNYOY-UHFFFAOYSA-N 4-bromo-2-fluorobenzenethiol Chemical compound FC1=CC(Br)=CC=C1S KENIDQSHNHNYOY-UHFFFAOYSA-N 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
- UUAVJCDYOHIIQW-UHFFFAOYSA-N 4-sulfonylpyridazin-3-one Chemical class O=C1N=NC=CC1=S(=O)=O UUAVJCDYOHIIQW-UHFFFAOYSA-N 0.000 description 1
- UYWAYTBDMJFIQT-UHFFFAOYSA-N 5-chloro-1h-pyridazin-6-one Chemical class ClC1=CC=NNC1=O UYWAYTBDMJFIQT-UHFFFAOYSA-N 0.000 description 1
- UOPQXNLLAZIGIK-UHFFFAOYSA-N 6-methoxy-2-sulfanyl-1h-pyridazine Chemical compound COC1=CC=CN(S)N1 UOPQXNLLAZIGIK-UHFFFAOYSA-N 0.000 description 1
- DEOUMTQMSUOBRR-UHFFFAOYSA-N 6-oxo-n-phenyl-n-propan-2-yl-1h-pyridazine-3-sulfonamide Chemical compound C1=CC(=O)NN=C1S(=O)(=O)N(C(C)C)C1=CC=CC=C1 DEOUMTQMSUOBRR-UHFFFAOYSA-N 0.000 description 1
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- MNQZXJOMYWMBOU-VKHMYHEASA-N D-glyceraldehyde Chemical compound OC[C@@H](O)C=O MNQZXJOMYWMBOU-VKHMYHEASA-N 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 108020005199 Dehydrogenases Proteins 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010009384 L-Iditol 2-Dehydrogenase Proteins 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000283977 Oryctolagus Species 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 102100026974 Sorbitol dehydrogenase Human genes 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- RGTGNSLGFMHBDM-UHFFFAOYSA-J [Zn++].[Cd++].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O Chemical compound [Zn++].[Cd++].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RGTGNSLGFMHBDM-UHFFFAOYSA-J 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- QGAQQANQFMOQTQ-UHFFFAOYSA-N acetic acid;2h-pyrido[3,2-c]pyridazin-3-one Chemical class CC(O)=O.N1=CC=CC2=NNC(=O)C=C21 QGAQQANQFMOQTQ-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001323 aldoses Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003545 alkoxy 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
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000002253 anti-ischaemic effect Effects 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000004321 blink reflex Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000003683 cardiac damage Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 210000000695 crystalline len Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- DXVYLFHTJZWTRF-UHFFFAOYSA-N ethyl iso-butyl ketone Natural products CCC(=O)CC(C)C DXVYLFHTJZWTRF-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- AXLHVTKGDPVANO-UHFFFAOYSA-N methyl 2-amino-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound COC(=O)C(N)CNC(=O)OC(C)(C)C AXLHVTKGDPVANO-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- VMOWKUTXPNPTEN-UHFFFAOYSA-N n,n-dimethylpropan-2-amine Chemical compound CC(C)N(C)C VMOWKUTXPNPTEN-UHFFFAOYSA-N 0.000 description 1
- FYOWLQRGZIBJQU-UHFFFAOYSA-N n-(3,4-dichlorophenyl)-n-methyl-6-oxo-1h-pyridazine-3-sulfonamide Chemical compound C1=CC(=O)NN=C1S(=O)(=O)N(C)C1=CC=C(Cl)C(Cl)=C1 FYOWLQRGZIBJQU-UHFFFAOYSA-N 0.000 description 1
- HUMMCEUVDBVXTQ-UHFFFAOYSA-N naphthalen-1-ylboronic acid Chemical compound C1=CC=C2C(B(O)O)=CC=CC2=C1 HUMMCEUVDBVXTQ-UHFFFAOYSA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- BHZRJJOHZFYXTO-UHFFFAOYSA-L potassium sulfite Chemical compound [K+].[K+].[O-]S([O-])=O BHZRJJOHZFYXTO-UHFFFAOYSA-L 0.000 description 1
- 235000019252 potassium sulphite Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000004892 pyridazines Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- CANIXWVJAIVMDB-UHFFFAOYSA-M sodium 3-(trifluoromethyl)benzenesulfonate Chemical compound [Na+].[O-]S(=O)(=O)c1cccc(c1)C(F)(F)F CANIXWVJAIVMDB-UHFFFAOYSA-M 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- PUGUQINMNYINPK-UHFFFAOYSA-N tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CCl)CC1 PUGUQINMNYINPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29339301P | 2001-05-24 | 2001-05-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK7332002A3 true SK7332002A3 (en) | 2003-05-02 |
Family
ID=23128899
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK733-2002A SK7332002A3 (en) | 2001-05-24 | 2002-05-24 | Method of reducing tissue damage associated with ischemia |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US6872722B2 (https=) |
| EP (1) | EP1260224B1 (https=) |
| JP (1) | JP2002370984A (https=) |
| KR (1) | KR20020090321A (https=) |
| CN (1) | CN1390547A (https=) |
| AT (1) | ATE289510T1 (https=) |
| AU (1) | AU761191B2 (https=) |
| CA (1) | CA2387007A1 (https=) |
| CZ (1) | CZ20021782A3 (https=) |
| DE (1) | DE60203026T2 (https=) |
| ES (1) | ES2236447T3 (https=) |
| HU (1) | HUP0201738A3 (https=) |
| PL (1) | PL354128A1 (https=) |
| SK (1) | SK7332002A3 (https=) |
| ZA (1) | ZA200203985B (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1236720B1 (en) * | 2001-02-28 | 2005-06-15 | Pfizer Products Inc. | Sulfonyl pyridazinone compounds useful as aldose reductase inhibitors |
| DK1961420T3 (da) * | 2005-12-16 | 2012-08-27 | Sanwa Kagaku Kenkyusho Co | Middel til forebyggelse og behandling af akut nyresvigt |
| KR20080108465A (ko) * | 2006-02-20 | 2008-12-15 | 가부시키가이샤산와카가쿠켄큐쇼 | 뇌졸중에 있어서의 뇌허혈 또는 뇌허혈 재관류 장해의 예방또는 치료제 |
| WO2022197487A1 (en) | 2021-03-18 | 2022-09-22 | Banavara MYLARI | Combination of aldose reductase inhibitors and probenecid for the treatment of diabetic complications |
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 |
| JPH01258671A (ja) * | 1987-12-01 | 1989-10-16 | Morishita Pharmaceut Co Ltd | ５−（１ｈ−イミダゾール−１−イル）−３（２ｈ）−ピリダジノン誘導体 |
| US4996204A (en) | 1989-05-11 | 1991-02-26 | Pfizer Inc. | Pyrido[2,3-d]pyridazinones as aldose reductase inhibitors |
| WO1992017446A2 (en) * | 1991-03-28 | 1992-10-15 | Pfizer Inc. | Pyridazinone acetic acids aldose reductase inhibitors |
| 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 |
| US5506228A (en) * | 1995-02-23 | 1996-04-09 | Merck & Co., Inc. | 2,6-diaryl pyridazinones with immunosuppressant activity |
| US5670504A (en) * | 1995-02-23 | 1997-09-23 | Merck & Co. Inc. | 2,6-diaryl pyridazinones with immunosuppressant activity |
| CN1142148C (zh) * | 1997-11-19 | 2004-03-17 | 兴和株式会社 | 新颖的哒嗪衍生物和含有其作为有效成分的药物 |
| TWI241295B (en) * | 1998-03-02 | 2005-10-11 | Kowa Co | Pyridazine derivative and medicine containing the same as effect component |
| JP2000247959A (ja) * | 1999-02-26 | 2000-09-12 | Kowa Co | ピリダジン−３−オン誘導体及びこれを含有する医薬 |
| EP1236720B1 (en) * | 2001-02-28 | 2005-06-15 | Pfizer Products Inc. | Sulfonyl pyridazinone compounds useful as aldose reductase inhibitors |
| CA2442476A1 (en) * | 2001-03-30 | 2002-10-10 | Pfizer Products Inc. | Pyridazinone aldose reductase inhibitors |
-
2002
- 2002-05-16 AU AU40685/02A patent/AU761191B2/en not_active Ceased
- 2002-05-17 CA CA002387007A patent/CA2387007A1/en not_active Abandoned
- 2002-05-20 JP JP2002144503A patent/JP2002370984A/ja active Pending
- 2002-05-20 ZA ZA200203985A patent/ZA200203985B/xx unknown
- 2002-05-22 ES ES02253605T patent/ES2236447T3/es not_active Expired - Lifetime
- 2002-05-22 DE DE60203026T patent/DE60203026T2/de not_active Expired - Fee Related
- 2002-05-22 CZ CZ20021782A patent/CZ20021782A3/cs unknown
- 2002-05-22 EP EP02253605A patent/EP1260224B1/en not_active Expired - Lifetime
- 2002-05-22 AT AT02253605T patent/ATE289510T1/de not_active IP Right Cessation
- 2002-05-23 HU HU0201738A patent/HUP0201738A3/hu unknown
- 2002-05-23 US US10/154,694 patent/US6872722B2/en not_active Expired - Fee Related
- 2002-05-23 KR KR1020020028665A patent/KR20020090321A/ko not_active Ceased
- 2002-05-24 PL PL02354128A patent/PL354128A1/xx not_active Application Discontinuation
- 2002-05-24 SK SK733-2002A patent/SK7332002A3/sk unknown
- 2002-05-24 CN CN02120397A patent/CN1390547A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US6872722B2 (en) | 2005-03-29 |
| AU761191B2 (en) | 2003-05-29 |
| EP1260224B1 (en) | 2005-02-23 |
| JP2002370984A (ja) | 2002-12-24 |
| DE60203026D1 (de) | 2005-03-31 |
| CN1390547A (zh) | 2003-01-15 |
| CZ20021782A3 (cs) | 2003-03-12 |
| EP1260224A1 (en) | 2002-11-27 |
| HUP0201738A2 (hu) | 2003-02-28 |
| ES2236447T3 (es) | 2005-07-16 |
| HUP0201738A3 (en) | 2003-11-28 |
| ATE289510T1 (de) | 2005-03-15 |
| US20030008871A1 (en) | 2003-01-09 |
| ZA200203985B (en) | 2003-11-20 |
| DE60203026T2 (de) | 2006-05-04 |
| PL354128A1 (en) | 2002-12-02 |
| KR20020090321A (ko) | 2002-12-02 |
| AU4068502A (en) | 2002-11-28 |
| HU0201738D0 (https=) | 2002-07-29 |
| CA2387007A1 (en) | 2002-11-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2054004C1 (ru) | Производные 3(2н)-пиридазинона или их фармацевтически приемлемые соли и фармацевтическая композиция на их основе | |
| KR102304121B1 (ko) | 심장 상태에 대한 피리미딘디온 화합물 | |
| SK13812000A3 (sk) | Benzénsulfónamidové deriváty, spôsob ich prípravy, ich použitie a farmaceutická kompozícia, ktorá ich obsahuje | |
| JPWO1991016314A1 (ja) | ピリダジノン誘導体 | |
| AU2005226359A1 (en) | 9-substituted 8-oxoadenine compound | |
| EP0751132B1 (en) | Pyridazinone derivatives and processes for preparing the same | |
| US6730674B2 (en) | Sulfonyl pyridazinone compounds useful as aldose reductase inhibitors | |
| SK7332002A3 (en) | Method of reducing tissue damage associated with ischemia | |
| EP0661274A1 (en) | Indane derivatives, processes for preparing the same and synthetic intermediate of the same | |
| DE19832428A1 (de) | Imidazolderivate mit Biphenylsulfonylsubstitution, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament | |
| US8853248B2 (en) | (1,2,3-triazolyl)sulfonyl derivatives | |
| AU2002236131B2 (en) | Combinations of aldose reductase inhibitors and cyclooxygenase-2 inhibitors | |
| US7582676B2 (en) | 2-phenylpyran-4-one derivatives as selective COX-2 inhibitors | |
| US5686452A (en) | Indane derivative and processes for preparing the same | |
| AU2002236131A1 (en) | Combinations of aldose reductase inhibitors and cyclooxygenase-2 inhibitors | |
| US20230013304A1 (en) | N2-arylmethyl-4-haloalkyl-pyridazin-3-one cftr modulators for the treatment of cystic fibrosis | |
| JPH07224045A (ja) | ピリダジノン誘導体，その製法及びその用途 |