UA71892C2 - Sulfonamide derivatives - Google Patents
Sulfonamide derivatives Download PDFInfo
- Publication number
- UA71892C2 UA71892C2 UA99084464A UA99084464A UA71892C2 UA 71892 C2 UA71892 C2 UA 71892C2 UA 99084464 A UA99084464 A UA 99084464A UA 99084464 A UA99084464 A UA 99084464A UA 71892 C2 UA71892 C2 UA 71892C2
- Authority
- UA
- Ukraine
- Prior art keywords
- phenyl
- alkyl
- group
- mmol
- propyl
- Prior art date
Links
- 229940124530 sulfonamide Drugs 0.000 title claims description 8
- 150000003456 sulfonamides Chemical class 0.000 title claims description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 301
- -1 morpholino, piperazinyl Chemical group 0.000 claims abstract description 256
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 169
- 238000000034 method Methods 0.000 claims abstract description 116
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 100
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 27
- 125000001424 substituent group Chemical group 0.000 claims abstract description 26
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 25
- 125000003118 aryl group Chemical group 0.000 claims abstract description 23
- 125000002393 azetidinyl group Chemical group 0.000 claims abstract description 23
- 125000005843 halogen group Chemical group 0.000 claims abstract description 23
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 16
- 102000018899 Glutamate Receptors Human genes 0.000 claims abstract description 14
- 108010027915 Glutamate Receptors Proteins 0.000 claims abstract description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 11
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 59
- 239000001257 hydrogen Substances 0.000 claims description 49
- 229910052739 hydrogen Inorganic materials 0.000 claims description 49
- 230000015572 biosynthetic process Effects 0.000 claims description 44
- 150000004820 halides Chemical class 0.000 claims description 33
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 32
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
- 125000000335 thiazolyl group Chemical group 0.000 claims description 19
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 18
- 125000001544 thienyl group Chemical group 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 125000002541 furyl group Chemical group 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 15
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 claims description 12
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000002883 imidazolyl group Chemical group 0.000 claims description 11
- 125000001041 indolyl group Chemical group 0.000 claims description 11
- 125000002971 oxazolyl group Chemical group 0.000 claims description 11
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 11
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 10
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 9
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 9
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 9
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims description 9
- 125000005072 dihydrothiopyranyl group Chemical group S1C(CCC=C1)* 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 9
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 9
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 8
- 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 description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 7
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 7
- 125000005056 dihydrothiazolyl group Chemical group S1C(NC=C1)* 0.000 claims description 7
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 7
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 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 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 claims description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 3
- 230000002708 enhancing effect Effects 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 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 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical group NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 1
- 241000343235 Maso Species 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- 210000005056 cell body Anatomy 0.000 claims 1
- 229940126601 medicinal product Drugs 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
- 238000012876 topography Methods 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 abstract description 38
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 30
- 125000003545 alkoxy group Chemical group 0.000 abstract description 9
- 125000002947 alkylene group Chemical group 0.000 abstract description 7
- 229910052736 halogen Inorganic materials 0.000 abstract description 7
- 241000124008 Mammalia Species 0.000 abstract description 4
- 125000004965 chloroalkyl group Chemical group 0.000 abstract description 3
- 125000003709 fluoroalkyl group Chemical group 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 629
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 407
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 333
- 239000000243 solution Substances 0.000 description 314
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 212
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 208
- 239000000203 mixture Substances 0.000 description 208
- 238000001819 mass spectrum Methods 0.000 description 178
- 239000013067 intermediate product Substances 0.000 description 143
- 239000000543 intermediate Substances 0.000 description 138
- 239000000047 product Substances 0.000 description 135
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 134
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 118
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 111
- 239000012044 organic layer Substances 0.000 description 110
- 239000003480 eluent Substances 0.000 description 107
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 106
- 235000019341 magnesium sulphate Nutrition 0.000 description 106
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 102
- 239000010410 layer Substances 0.000 description 99
- 239000000741 silica gel Substances 0.000 description 99
- 229910002027 silica gel Inorganic materials 0.000 description 99
- 238000003795 desorption Methods 0.000 description 88
- 238000004587 chromatography analysis Methods 0.000 description 87
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 72
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 70
- 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 69
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 66
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 59
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 53
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 49
- 239000007864 aqueous solution Substances 0.000 description 45
- 238000003786 synthesis reaction Methods 0.000 description 40
- 239000007787 solid Substances 0.000 description 36
- 229910000027 potassium carbonate Inorganic materials 0.000 description 35
- 235000011181 potassium carbonates Nutrition 0.000 description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 32
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 31
- 238000004364 calculation method Methods 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
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
- 239000000284 extract Substances 0.000 description 29
- 239000003921 oil Substances 0.000 description 29
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 28
- 239000012267 brine Substances 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 27
- 238000004458 analytical method Methods 0.000 description 25
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 25
- 235000019441 ethanol Nutrition 0.000 description 24
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 23
- 238000010992 reflux Methods 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
- 125000000304 alkynyl group Chemical group 0.000 description 21
- 239000000725 suspension Substances 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 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 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
- 229910052938 sodium sulfate Inorganic materials 0.000 description 19
- 235000011152 sodium sulphate Nutrition 0.000 description 19
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-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
- 239000012265 solid product Substances 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 238000011097 chromatography purification Methods 0.000 description 15
- DRINJBFRTLBHNF-UHFFFAOYSA-N propane-2-sulfonyl chloride Chemical compound CC(C)S(Cl)(=O)=O DRINJBFRTLBHNF-UHFFFAOYSA-N 0.000 description 15
- 230000006870 function Effects 0.000 description 14
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 14
- 102000005962 receptors Human genes 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
- 238000010828 elution Methods 0.000 description 13
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 13
- 238000002844 melting Methods 0.000 description 13
- 230000008018 melting Effects 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- 238000001953 recrystallisation Methods 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 12
- 239000012043 crude product Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 229930195712 glutamate Natural products 0.000 description 12
- 239000000872 buffer Substances 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- 229910052740 iodine Inorganic materials 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
- BOCUKUHCLICSIY-QJWLJZLASA-N cyclothiazide Chemical compound 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
- 238000010438 heat treatment Methods 0.000 description 10
- 239000000556 agonist Substances 0.000 description 9
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- QMMFVYPAHWMCMS-UHFFFAOYSA-N dimethylsulfide Substances CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 8
- 239000003623 enhancer Substances 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
- 229910052763 palladium Inorganic materials 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 7
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 7
- 102000003678 AMPA Receptors Human genes 0.000 description 7
- 108090000078 AMPA Receptors Proteins 0.000 description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 239000011698 potassium fluoride Substances 0.000 description 7
- 235000003270 potassium fluoride Nutrition 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 7
- DCTOHCCUXLBQMS-UHFFFAOYSA-N 1-undecene Chemical compound CCCCCCCCCC=C DCTOHCCUXLBQMS-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000000010 aprotic solvent Substances 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
- 150000002367 halogens Chemical class 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- UUDAMDVQRQNNHZ-UHFFFAOYSA-N (S)-AMPA Chemical compound CC=1ONC(=O)C=1CC(N)C(O)=O UUDAMDVQRQNNHZ-UHFFFAOYSA-N 0.000 description 5
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
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- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000003956 synaptic plasticity Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- LZUIXTILDJMTAJ-UHFFFAOYSA-N tert-butyl 5-amino-2-bromobenzoate Chemical compound CC(C)(C)OC(=O)C1=CC(N)=CC=C1Br LZUIXTILDJMTAJ-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 1
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 1
- QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 230000018405 transmission of nerve impulse Effects 0.000 description 1
- SANWDQJIWZEKOD-UHFFFAOYSA-N tributyl(furan-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CO1 SANWDQJIWZEKOD-UHFFFAOYSA-N 0.000 description 1
- 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
- JKVRTUCVPZTEQZ-UHFFFAOYSA-N tributyltin azide Chemical compound CCCC[Sn](CCCC)(CCCC)N=[N+]=[N-] JKVRTUCVPZTEQZ-UHFFFAOYSA-N 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
- DZJXLMSJAUYLCS-UHFFFAOYSA-N trimethyl(1,3-thiazol-2-yl)stannane Chemical compound C[Sn](C)(C)C1=NC=CS1 DZJXLMSJAUYLCS-UHFFFAOYSA-N 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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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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PCT/US1998/001881 WO1998033496A1 (en) | 1997-02-04 | 1998-01-30 | Sulphonamide derivatives |
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US6613804B2 (en) | 1993-05-20 | 2003-09-02 | Encysive Pharmaceuticals, Inc. | Biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin |
US5877193A (en) * | 1996-07-19 | 1999-03-02 | Hoffmann-La Roche Inc. | Use of N-(4-aryl-thiazol-2-yl)-sulfonamides |
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- 1998-01-30 UA UA99084464A patent/UA71892C2/uk unknown
- 1998-01-30 NZ NZ336559A patent/NZ336559A/xx unknown
- 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 ID IDW990754A patent/ID22500A/id unknown
- 1998-01-30 JP JP53314498A patent/JP2001511781A/ja not_active Ceased
- 1998-01-30 WO PCT/US1998/001881 patent/WO1998033496A1/en not_active Application Discontinuation
- 1998-01-30 IL IL13097098A patent/IL130970A/xx not_active IP Right Cessation
- 1998-01-30 AU AU62595/98A patent/AU760056B2/en not_active Ceased
- 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 AT AT98300759T patent/ATE284385T1/de not_active IP Right Cessation
- 1998-02-03 EP EP98300759A patent/EP0860428B1/en 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 DE DE69827984T patent/DE69827984T2/de not_active Expired - Lifetime
- 1998-02-03 PT PT98300759T patent/PT860428E/pt unknown
- 1998-02-03 ES ES98300759T patent/ES2232914T3/es 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
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1999
- 1999-07-28 NO NO993667A patent/NO993667L/no not_active Application Discontinuation
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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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