EA001919B1 - Сульфонамидные производные - Google Patents
Сульфонамидные производные Download PDFInfo
- Publication number
- EA001919B1 EA001919B1 EA199900719A EA199900719A EA001919B1 EA 001919 B1 EA001919 B1 EA 001919B1 EA 199900719 A EA199900719 A EA 199900719A EA 199900719 A EA199900719 A EA 199900719A EA 001919 B1 EA001919 B1 EA 001919B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- alkyl
- phenyl
- group
- alkenyl
- cycloalkyl
- Prior art date
Links
- 150000003456 sulfonamides Chemical class 0.000 title description 7
- -1 (C1-C6)-chloroalkyl Chemical group 0.000 claims abstract description 382
- 150000001875 compounds Chemical class 0.000 claims abstract description 300
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 111
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims abstract description 108
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 93
- 239000001257 hydrogen Substances 0.000 claims abstract description 89
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 83
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 72
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 65
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 53
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 46
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 46
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 45
- 125000001424 substituent group Chemical group 0.000 claims abstract description 45
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 43
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 42
- 150000002367 halogens Chemical group 0.000 claims abstract description 41
- 125000002393 azetidinyl group Chemical group 0.000 claims abstract description 40
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims abstract description 38
- 125000003118 aryl group Chemical group 0.000 claims abstract description 34
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 33
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 32
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 32
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 30
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 29
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 28
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 27
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims abstract description 26
- 125000002541 furyl group Chemical group 0.000 claims abstract description 25
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 24
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 22
- 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 22
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 21
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims abstract description 18
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 18
- 125000000842 isoxazolyl group Chemical group 0.000 claims abstract description 18
- 125000002971 oxazolyl group Chemical group 0.000 claims abstract description 18
- 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 18
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 18
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims abstract description 17
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims abstract description 17
- 125000001041 indolyl group Chemical group 0.000 claims abstract description 17
- 125000002098 pyridazinyl group Chemical group 0.000 claims abstract description 17
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims abstract description 16
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims abstract description 16
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 16
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims abstract description 16
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims abstract description 16
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims abstract description 16
- 102000018899 Glutamate Receptors Human genes 0.000 claims abstract description 15
- 108010027915 Glutamate Receptors Proteins 0.000 claims abstract description 15
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 claims abstract description 15
- 125000005072 dihydrothiopyranyl group Chemical group S1C(CCC=C1)* 0.000 claims abstract description 15
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 13
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 12
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 11
- 125000005056 dihydrothiazolyl group Chemical group S1C(NC=C1)* 0.000 claims abstract description 11
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims abstract description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 10
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 10
- 230000003389 potentiating effect Effects 0.000 claims abstract description 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 9
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims abstract description 9
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 9
- 125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 claims abstract description 9
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims abstract description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 7
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 7
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims abstract description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims abstract description 5
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims description 165
- 125000000304 alkynyl group Chemical group 0.000 claims description 42
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 38
- VBYBSBGCKDDXBU-UHFFFAOYSA-N hexane-2-sulfonamide Chemical compound CCCCC(C)S(N)(=O)=O VBYBSBGCKDDXBU-UHFFFAOYSA-N 0.000 claims description 37
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 21
- 125000003342 alkenyl group Chemical group 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 17
- 230000006870 function Effects 0.000 claims description 14
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 8
- 229910052700 potassium Inorganic materials 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- 208000028017 Psychotic disease Diseases 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 125000004965 chloroalkyl group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 230000003993 interaction Effects 0.000 claims description 6
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 5
- 229960000846 camphor Drugs 0.000 claims description 5
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical group C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 claims description 4
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 241000723346 Cinnamomum camphora Species 0.000 claims description 4
- 229930008380 camphor Chemical group 0.000 claims description 4
- 125000002837 carbocyclic group Chemical group 0.000 claims description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 208000010877 cognitive disease Diseases 0.000 claims description 3
- OOPVMFMDPJFBFN-UHFFFAOYSA-N n-propylpropane-2-sulfonamide Chemical compound CCCNS(=O)(=O)C(C)C OOPVMFMDPJFBFN-UHFFFAOYSA-N 0.000 claims description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 2
- 208000028698 Cognitive impairment Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 208000016285 Movement disease Diseases 0.000 claims description 2
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 2
- 230000006735 deficit Effects 0.000 claims description 2
- 206010027175 memory impairment Diseases 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 229910052727 yttrium Inorganic materials 0.000 claims description 2
- ULRDYYKSPCRXAJ-UHFFFAOYSA-N n-[2-[4-[4-[2-(methanesulfonamido)ethyl]phenyl]phenyl]propyl]propane-2-sulfonamide Chemical compound C1=CC(C(C)CNS(=O)(=O)C(C)C)=CC=C1C1=CC=C(CCNS(C)(=O)=O)C=C1 ULRDYYKSPCRXAJ-UHFFFAOYSA-N 0.000 claims 3
- 235000015854 Heliotropium curassavicum Nutrition 0.000 claims 1
- 244000301682 Heliotropium curassavicum Species 0.000 claims 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical compound CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims 1
- 101000942305 Zea mays Cytokinin dehydrogenase 1 Proteins 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000006525 methoxy ethyl amino group Chemical group [H]N(*)C([H])([H])C([H])([H])OC([H])([H])[H] 0.000 claims 1
- CAKPWGVBMFDZGT-UONOGXRCSA-N n-[(1r,2s)-2-(3-cyclopentyloxy-4-methoxyphenyl)cyclopropyl]methanesulfonamide Chemical compound COC1=CC=C([C@H]2[C@@H](C2)NS(C)(=O)=O)C=C1OC1CCCC1 CAKPWGVBMFDZGT-UONOGXRCSA-N 0.000 claims 1
- GMWRZJCTZHAMDY-UHFFFAOYSA-N n-[2-[4-(4-aminophenyl)phenyl]propyl]propane-2-sulfonamide Chemical compound C1=CC(C(C)CNS(=O)(=O)C(C)C)=CC=C1C1=CC=C(N)C=C1 GMWRZJCTZHAMDY-UHFFFAOYSA-N 0.000 claims 1
- MJBBJUXMXHAVNW-UHFFFAOYSA-N n-[2-[4-[4-[1-(propan-2-ylsulfonylamino)propan-2-yl]phenyl]phenyl]ethyl]acetamide Chemical compound C1=CC(C(C)CNS(=O)(=O)C(C)C)=CC=C1C1=CC=C(CCNC(C)=O)C=C1 MJBBJUXMXHAVNW-UHFFFAOYSA-N 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 abstract description 13
- 125000004193 piperazinyl group Chemical group 0.000 abstract description 3
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 abstract 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 abstract 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 561
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 415
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 315
- 239000000243 solution Substances 0.000 description 251
- 239000000203 mixture Substances 0.000 description 245
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 188
- 239000000126 substance Substances 0.000 description 169
- 238000001819 mass spectrum Methods 0.000 description 167
- 238000000921 elemental analysis Methods 0.000 description 123
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 112
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 112
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 105
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 98
- 238000004587 chromatography analysis Methods 0.000 description 97
- 239000000741 silica gel Substances 0.000 description 88
- 229910002027 silica gel Inorganic materials 0.000 description 88
- 239000012044 organic layer Substances 0.000 description 85
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 84
- 239000000047 product Substances 0.000 description 84
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 82
- 238000003795 desorption Methods 0.000 description 76
- 239000010410 layer Substances 0.000 description 74
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 73
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 72
- 239000007787 solid Substances 0.000 description 58
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 56
- 239000011541 reaction mixture Substances 0.000 description 49
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- 239000007864 aqueous solution Substances 0.000 description 48
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 41
- 229910000027 potassium carbonate Inorganic materials 0.000 description 36
- 235000011181 potassium carbonates Nutrition 0.000 description 35
- 229940086542 triethylamine Drugs 0.000 description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 30
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 30
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 28
- 239000003921 oil Substances 0.000 description 28
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
- 238000004519 manufacturing process Methods 0.000 description 26
- 239000012267 brine Substances 0.000 description 25
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 22
- 229920006395 saturated elastomer Polymers 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 21
- 239000000284 extract Substances 0.000 description 21
- 239000000725 suspension Substances 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 18
- 235000019441 ethanol Nutrition 0.000 description 17
- 229910017976 MgO 4 Inorganic materials 0.000 description 16
- DRINJBFRTLBHNF-UHFFFAOYSA-N propane-2-sulfonyl chloride Chemical compound CC(C)S(Cl)(=O)=O DRINJBFRTLBHNF-UHFFFAOYSA-N 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 238000007872 degassing Methods 0.000 description 15
- 239000011777 magnesium Substances 0.000 description 15
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 14
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 14
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 13
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 11
- 239000000872 buffer Substances 0.000 description 11
- 229930195712 glutamate Natural products 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- BOCUKUHCLICSIY-QJWLJZLASA-N cyclothiazide Chemical group C1=C(Cl)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1NC2C1[C@H](C=C2)C[C@H]2C1 BOCUKUHCLICSIY-QJWLJZLASA-N 0.000 description 10
- 229960003176 cyclothiazide Drugs 0.000 description 10
- 238000010828 elution Methods 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 239000000556 agonist Substances 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- 239000012047 saturated solution Substances 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- 102000003678 AMPA Receptors Human genes 0.000 description 7
- 108090000078 AMPA Receptors Proteins 0.000 description 7
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 7
- 239000011698 potassium fluoride Substances 0.000 description 7
- 235000003270 potassium fluoride Nutrition 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- UUDAMDVQRQNNHZ-UHFFFAOYSA-N (S)-AMPA Chemical compound CC=1ONC(=O)C=1CC(N)C(O)=O UUDAMDVQRQNNHZ-UHFFFAOYSA-N 0.000 description 6
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 6
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
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- VTEKJMLRRQTTAX-UHFFFAOYSA-N tributyl(furan-3-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=1C=COC=1 VTEKJMLRRQTTAX-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
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- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
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- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/28—Halogen atoms
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- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
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- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D333/58—Radicals substituted by nitrogen atoms
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- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes 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
- C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
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| CN115605457B (zh) * | 2021-04-26 | 2025-03-18 | 三菱瓦斯化学株式会社 | 化合物及其制造方法 |
| CN114436911B (zh) * | 2022-03-17 | 2023-04-28 | 南京林业大学 | 一种樟脑磺酰苄胺类化合物的制备方法及其应用 |
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-
1998
- 1998-01-30 NZ NZ336559A patent/NZ336559A/xx unknown
- 1998-01-30 HU HU0002208A patent/HUP0002208A3/hu unknown
- 1998-01-30 JP JP53314498A patent/JP2001511781A/ja not_active Ceased
- 1998-01-30 ID IDW990754A patent/ID22500A/id unknown
- 1998-01-30 EA EA199900719A patent/EA001919B1/ru not_active IP Right Cessation
- 1998-01-30 KR KR1019997007012A patent/KR20000070753A/ko not_active Ceased
- 1998-01-30 AU AU62595/98A patent/AU760056B2/en not_active Ceased
- 1998-01-30 IL IL13097098A patent/IL130970A/xx not_active IP Right Cessation
- 1998-01-30 WO PCT/US1998/001881 patent/WO1998033496A1/en not_active Ceased
- 1998-01-30 BR BR9807297-8A patent/BR9807297A/pt not_active Application Discontinuation
- 1998-01-30 PL PL98334963A patent/PL334963A1/xx not_active Application Discontinuation
- 1998-01-30 CN CN98803753A patent/CN1251523A/zh active Pending
- 1998-01-30 TR TR1999/02368T patent/TR199902368T2/xx unknown
- 1998-01-30 UA UA99084464A patent/UA71892C2/uk unknown
- 1998-01-30 CA CA002278790A patent/CA2278790A1/en not_active Abandoned
- 1998-02-02 ZA ZA9800842A patent/ZA98842B/xx unknown
- 1998-02-02 CO CO98004892A patent/CO5080767A1/es unknown
- 1998-02-03 DE DE69827984T patent/DE69827984T2/de not_active Expired - Lifetime
- 1998-02-03 SI SI9830743T patent/SI0860428T1/xx unknown
- 1998-02-03 DK DK98300759T patent/DK0860428T3/da active
- 1998-02-03 EP EP04104929A patent/EP1528055A2/en not_active Withdrawn
- 1998-02-03 ES ES98300759T patent/ES2232914T3/es not_active Expired - Lifetime
- 1998-02-03 AT AT98300759T patent/ATE284385T1/de not_active IP Right Cessation
- 1998-02-03 PT PT98300759T patent/PT860428E/pt unknown
- 1998-02-03 EP EP98300759A patent/EP0860428B1/en not_active Expired - Lifetime
- 1998-02-04 PE PE1998000078A patent/PE72899A1/es not_active Application Discontinuation
- 1998-02-04 AR ARP980100477A patent/AR011623A1/es unknown
-
1999
- 1999-07-28 NO NO993667A patent/NO993667L/no not_active Application Discontinuation
-
2001
- 2001-07-25 US US09/912,809 patent/US6596716B2/en not_active Expired - Fee Related
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2003
- 2003-05-29 US US10/447,619 patent/US7135487B2/en not_active Expired - Fee Related
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM RU |