AU760056B2 - Sulphonamide derivatives - Google Patents
Sulphonamide derivatives Download PDFInfo
- Publication number
- AU760056B2 AU760056B2 AU62595/98A AU6259598A AU760056B2 AU 760056 B2 AU760056 B2 AU 760056B2 AU 62595/98 A AU62595/98 A AU 62595/98A AU 6259598 A AU6259598 A AU 6259598A AU 760056 B2 AU760056 B2 AU 760056B2
- Authority
- AU
- Australia
- Prior art keywords
- alkyl
- phenyl
- group
- alkenyl
- cycloalkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 150000003456 sulfonamides Chemical class 0.000 title description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 614
- -1 hydroxyimino Chemical group 0.000 claims description 459
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 265
- 125000003342 alkenyl group Chemical group 0.000 claims description 257
- 150000001875 compounds Chemical class 0.000 claims description 216
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 196
- 229910052739 hydrogen Inorganic materials 0.000 claims description 178
- 239000001257 hydrogen Substances 0.000 claims description 174
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 152
- 125000000304 alkynyl group Chemical group 0.000 claims description 145
- 238000002360 preparation method Methods 0.000 claims description 137
- 125000003118 aryl group Chemical group 0.000 claims description 135
- 229910052736 halogen Inorganic materials 0.000 claims description 132
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 131
- 150000002367 halogens Chemical class 0.000 claims description 120
- 229910052757 nitrogen Inorganic materials 0.000 claims description 108
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 106
- 125000003386 piperidinyl group Chemical group 0.000 claims description 105
- 125000002393 azetidinyl group Chemical group 0.000 claims description 101
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 98
- 125000003545 alkoxy group Chemical group 0.000 claims description 94
- 125000005843 halogen group Chemical group 0.000 claims description 91
- 125000001424 substituent group Chemical group 0.000 claims description 78
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 77
- 125000004432 carbon atom Chemical group C* 0.000 claims description 75
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 71
- 125000001072 heteroaryl group Chemical group 0.000 claims description 64
- 229910052717 sulfur Inorganic materials 0.000 claims description 62
- 125000002947 alkylene group Chemical group 0.000 claims description 58
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 56
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 53
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 51
- 238000000034 method Methods 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 45
- 125000004076 pyridyl group Chemical group 0.000 claims description 43
- 229910052799 carbon Inorganic materials 0.000 claims description 42
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 42
- 125000001544 thienyl group Chemical group 0.000 claims description 42
- 229910052760 oxygen Inorganic materials 0.000 claims description 40
- 125000002837 carbocyclic group Chemical group 0.000 claims description 38
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 38
- 125000000335 thiazolyl group Chemical group 0.000 claims description 38
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 37
- 125000002883 imidazolyl group Chemical group 0.000 claims description 37
- 125000001041 indolyl group Chemical group 0.000 claims description 37
- 125000002971 oxazolyl group Chemical group 0.000 claims description 37
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 37
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 37
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 37
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 35
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims description 35
- 125000005072 dihydrothiopyranyl group Chemical group S1C(CCC=C1)* 0.000 claims description 35
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 35
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 35
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 35
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 claims description 34
- 125000002541 furyl group Chemical group 0.000 claims description 34
- 125000001188 haloalkyl group Chemical group 0.000 claims description 33
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 32
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 32
- 125000005056 dihydrothiazolyl group Chemical group S1C(NC=C1)* 0.000 claims description 31
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 31
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 claims description 29
- 125000001624 naphthyl group Chemical group 0.000 claims description 29
- 125000004965 chloroalkyl group Chemical group 0.000 claims description 27
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 26
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 26
- 208000028017 Psychotic disease Diseases 0.000 claims description 26
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 26
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 25
- 230000006870 function Effects 0.000 claims description 24
- 102000018899 Glutamate Receptors Human genes 0.000 claims description 23
- 108010027915 Glutamate Receptors Proteins 0.000 claims description 23
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 23
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
- 230000003389 potentiating effect Effects 0.000 claims description 21
- 241000124008 Mammalia Species 0.000 claims description 19
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 13
- 206010012289 Dementia Diseases 0.000 claims description 13
- 208000016285 Movement disease Diseases 0.000 claims description 13
- 208000011963 Substance-induced psychotic disease Diseases 0.000 claims description 13
- 231100000393 Substance-induced psychotic disorder Toxicity 0.000 claims description 13
- 230000007278 cognition impairment Effects 0.000 claims description 13
- 208000010877 cognitive disease Diseases 0.000 claims description 13
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 13
- 201000002545 drug psychosis Diseases 0.000 claims description 13
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 13
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 13
- 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 12
- 229940079593 drug Drugs 0.000 claims description 12
- 206010027175 memory impairment Diseases 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- 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 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 10
- 125000004429 atom Chemical group 0.000 claims description 10
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 9
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 9
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 8
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 5
- VBYBSBGCKDDXBU-UHFFFAOYSA-N hexane-2-sulfonamide Chemical compound CCCCC(C)S(N)(=O)=O VBYBSBGCKDDXBU-UHFFFAOYSA-N 0.000 claims description 5
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- 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
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 3
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 3
- UZIFXXBGOQDTCA-UHFFFAOYSA-N n-(2,2-diphenylethyl)methanesulfonamide Chemical compound C=1C=CC=CC=1C(CNS(=O)(=O)C)C1=CC=CC=C1 UZIFXXBGOQDTCA-UHFFFAOYSA-N 0.000 claims description 3
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 4
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims 1
- 101150065749 Churc1 gene Proteins 0.000 claims 1
- 101100440695 Dictyostelium discoideum corB gene Proteins 0.000 claims 1
- 102100030669 Glutamate receptor 3 Human genes 0.000 claims 1
- 101710087630 Glutamate receptor 3 Proteins 0.000 claims 1
- 101000583150 Homo sapiens Membrane-associated phosphatidylinositol transfer protein 3 Proteins 0.000 claims 1
- 102100030351 Membrane-associated phosphatidylinositol transfer protein 3 Human genes 0.000 claims 1
- DZSYJVXGONVNKA-UHFFFAOYSA-L NIR-1 dye Chemical compound [K+].[K+].C1=CC2=C(S([O-])(=O)=O)C=C(S([O-])(=O)=O)C=C2C(C2(C)C)=C1[N+](CC)=C2C=CC=CC=CC=C1C(C)(C)C2=CC(C(O)=O)=CC=C2N1CCCCS([O-])(=O)=O DZSYJVXGONVNKA-UHFFFAOYSA-L 0.000 claims 1
- 102100038239 Protein Churchill Human genes 0.000 claims 1
- 125000004799 bromophenyl group Chemical group 0.000 claims 1
- 230000006735 deficit Effects 0.000 claims 1
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims 1
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
- XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 186
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 126
- 239000000243 solution Substances 0.000 description 96
- 239000000203 mixture Substances 0.000 description 93
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 75
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 72
- 235000019439 ethyl acetate Nutrition 0.000 description 66
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 58
- 229940093499 ethyl acetate Drugs 0.000 description 54
- 238000001819 mass spectrum Methods 0.000 description 46
- 229910001868 water Inorganic materials 0.000 description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- 239000000047 product Substances 0.000 description 37
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 37
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- 239000000463 material Substances 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 24
- 239000010410 layer Substances 0.000 description 24
- 239000012044 organic layer Substances 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 238000004587 chromatography analysis Methods 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- 238000004458 analytical method Methods 0.000 description 17
- 238000003795 desorption Methods 0.000 description 17
- 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 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 239000012267 brine Substances 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 14
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- 238000005481 NMR spectroscopy Methods 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
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- 239000000872 buffer Substances 0.000 description 11
- 229930195712 glutamate Natural products 0.000 description 11
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 11
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
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- 229960003176 cyclothiazide Drugs 0.000 description 10
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- 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 9
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- 239000004480 active ingredient Substances 0.000 description 8
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- 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 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
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- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
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- AEHDSYHVTDJGDN-UHFFFAOYSA-M phenacyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1C(=O)C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 AEHDSYHVTDJGDN-UHFFFAOYSA-M 0.000 description 5
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- GAIZFMKSOHADOV-UHFFFAOYSA-N tert-butyl n-methylsulfonylcarbamate Chemical compound CC(C)(C)OC(=O)NS(C)(=O)=O GAIZFMKSOHADOV-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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000004495 thiazol-4-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
- 239000003104 tissue culture media Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 230000018405 transmission of nerve impulse Effects 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
- 238000001665 trituration Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
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- 1998-01-30 ID IDW990754A patent/ID22500A/id unknown
- 1998-01-30 EA EA199900719A patent/EA001919B1/ru not_active IP Right Cessation
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1999
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2001
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0501322A1 (en) * | 1991-02-25 | 1992-09-02 | Glaxo Group Limited | 3-Piperidinylmethylcarboxylate substituted indoles |
| WO1993014745A1 (en) * | 1992-01-23 | 1993-08-05 | Smithkline Beecham Plc | Use of 5-ht4 receptor antagonists as medicaments for treating migraine |
| EP0655442A1 (en) * | 1993-11-29 | 1995-05-31 | Fujisawa Pharmaceutical Co., Ltd. | Piperazine derivatives as Tachykinin antagonists |
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