PT86702B - Processo para a prepapacao de metano-sulfonamido-fenetilaminas substituidas - Google Patents
Processo para a prepapacao de metano-sulfonamido-fenetilaminas substituidas Download PDFInfo
- Publication number
- PT86702B PT86702B PT86702A PT8670288A PT86702B PT 86702 B PT86702 B PT 86702B PT 86702 A PT86702 A PT 86702A PT 8670288 A PT8670288 A PT 8670288A PT 86702 B PT86702 B PT 86702B
- Authority
- PT
- Portugal
- Prior art keywords
- formula
- alkyl
- compound
- evaporated
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 19
- 230000008569 process Effects 0.000 title claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 27
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims description 73
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 38
- 238000002360 preparation method Methods 0.000 claims description 38
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 13
- -1 alkane chloride Chemical class 0.000 claims description 13
- 239000012359 Methanesulfonyl chloride Substances 0.000 claims description 12
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 2
- NQTLKOLFUZOZRM-UHFFFAOYSA-N n-[2-(chloromethyl)quinolin-6-yl]methanesulfonamide Chemical compound N1=C(CCl)C=CC2=CC(NS(=O)(=O)C)=CC=C21 NQTLKOLFUZOZRM-UHFFFAOYSA-N 0.000 claims description 2
- 241001331845 Equus asinus x caballus Species 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 102
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 69
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- 238000004519 manufacturing process Methods 0.000 description 26
- 239000000243 solution Substances 0.000 description 26
- 238000002844 melting Methods 0.000 description 25
- 230000008018 melting Effects 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 22
- 238000010992 reflux Methods 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 239000000203 mixture Substances 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 239000000377 silicon dioxide Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 7
- 230000037024 effective refractory period Effects 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000003416 antiarrhythmic agent Substances 0.000 description 6
- 206010003119 arrhythmia Diseases 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 5
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 230000001746 atrial effect Effects 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 3
- 230000006793 arrhythmia Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 235000009518 sodium iodide Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000002861 ventricular Effects 0.000 description 3
- QXHDYMUPPXAMPQ-UHFFFAOYSA-N 2-(4-aminophenyl)ethanol Chemical compound NC1=CC=C(CCO)C=C1 QXHDYMUPPXAMPQ-UHFFFAOYSA-N 0.000 description 2
- HXEURDRGGNKAJL-UHFFFAOYSA-N 2-[4-(methanesulfonamido)phenyl]ethyl methanesulfonate Chemical compound CS(=O)(=O)NC1=CC=C(CCOS(C)(=O)=O)C=C1 HXEURDRGGNKAJL-UHFFFAOYSA-N 0.000 description 2
- TYJFYUVDUUACKX-UHFFFAOYSA-N 2-methylquinolin-6-amine Chemical compound C1=C(N)C=CC2=NC(C)=CC=C21 TYJFYUVDUUACKX-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- 206010003658 Atrial Fibrillation Diseases 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 206010042600 Supraventricular arrhythmias Diseases 0.000 description 2
- 206010047281 Ventricular arrhythmia Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 210000002837 heart atrium Anatomy 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 2
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- VKCLRNSQZIAQRL-UHFFFAOYSA-N n-(2-methylquinolin-6-yl)methanesulfonamide Chemical compound C1=C(NS(C)(=O)=O)C=CC2=NC(C)=CC=C21 VKCLRNSQZIAQRL-UHFFFAOYSA-N 0.000 description 2
- IWBSMKCGMCVHFN-UHFFFAOYSA-N n-[4-[2-(ethylamino)ethyl]phenyl]methanesulfonamide Chemical compound CCNCCC1=CC=C(NS(C)(=O)=O)C=C1 IWBSMKCGMCVHFN-UHFFFAOYSA-N 0.000 description 2
- PTPPVTUXJDJAGY-UHFFFAOYSA-N n-methyl-2-(4-nitrophenyl)ethanamine Chemical compound CNCCC1=CC=C([N+]([O-])=O)C=C1 PTPPVTUXJDJAGY-UHFFFAOYSA-N 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 230000002028 premature Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 208000003663 ventricular fibrillation Diseases 0.000 description 2
- FLQLOSXUXIZANO-UHFFFAOYSA-N (3-methyl-5-nitro-1-benzofuran-2-yl)methanol Chemical compound C1=C([N+]([O-])=O)C=C2C(C)=C(CO)OC2=C1 FLQLOSXUXIZANO-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 1
- DTJDFRUXVBYSFS-UHFFFAOYSA-N 2-(2-bromoethyl)-5-nitro-1-benzofuran Chemical compound [O-][N+](=O)C1=CC=C2OC(CCBr)=CC2=C1 DTJDFRUXVBYSFS-UHFFFAOYSA-N 0.000 description 1
- SFJHMWIZTGVIBR-UHFFFAOYSA-N 2-(bromomethyl)-5-nitro-1-benzofuran Chemical compound [O-][N+](=O)C1=CC=C2OC(CBr)=CC2=C1 SFJHMWIZTGVIBR-UHFFFAOYSA-N 0.000 description 1
- HPRUEYFCCQNIAC-UHFFFAOYSA-N 2-(bromomethyl)-6-nitro-1-benzofuran Chemical compound [O-][N+](=O)C1=CC=C2C=C(CBr)OC2=C1 HPRUEYFCCQNIAC-UHFFFAOYSA-N 0.000 description 1
- BWRZMNAKJWZHKT-UHFFFAOYSA-N 2-(chloromethyl)-6-nitroquinoline Chemical compound N1=C(CCl)C=CC2=CC([N+](=O)[O-])=CC=C21 BWRZMNAKJWZHKT-UHFFFAOYSA-N 0.000 description 1
- VLZVIIYRNMWPSN-UHFFFAOYSA-N 2-Amino-4-nitrophenol Chemical compound NC1=CC([N+]([O-])=O)=CC=C1O VLZVIIYRNMWPSN-UHFFFAOYSA-N 0.000 description 1
- MDSLIRRIBIKJMN-UHFFFAOYSA-N 2-[[2-(4-aminophenyl)ethyl-methylamino]methyl]-1,3-benzoxazol-5-amine Chemical compound N=1C2=CC(N)=CC=C2OC=1CN(C)CCC1=CC=C(N)C=C1 MDSLIRRIBIKJMN-UHFFFAOYSA-N 0.000 description 1
- UGPFRPBHFMUHQE-UHFFFAOYSA-N 2-[[2-(4-aminophenyl)ethyl-methylamino]methyl]-1-benzofuran-5-amine Chemical compound C=1C2=CC(N)=CC=C2OC=1CN(C)CCC1=CC=C(N)C=C1 UGPFRPBHFMUHQE-UHFFFAOYSA-N 0.000 description 1
- AGRBVAOJFKSQDP-UHFFFAOYSA-N 2-[[2-(4-aminophenyl)ethyl-methylamino]methyl]quinolin-6-amine Chemical compound C=1C=C2C=C(N)C=CC2=NC=1CN(C)CCC1=CC=C(N)C=C1 AGRBVAOJFKSQDP-UHFFFAOYSA-N 0.000 description 1
- GDQWGORSGRIJCV-UHFFFAOYSA-N 2-methyl-5-nitro-1-benzofuran Chemical compound [O-][N+](=O)C1=CC=C2OC(C)=CC2=C1 GDQWGORSGRIJCV-UHFFFAOYSA-N 0.000 description 1
- OARGPFUERLBQDJ-UHFFFAOYSA-N 2-methyl-6-nitro-1-benzofuran Chemical compound C1=C([N+]([O-])=O)C=C2OC(C)=CC2=C1 OARGPFUERLBQDJ-UHFFFAOYSA-N 0.000 description 1
- DXDPHHQJZWWAEH-UHFFFAOYSA-N 2-methyl-6-nitroquinoline Chemical compound C1=C([N+]([O-])=O)C=CC2=NC(C)=CC=C21 DXDPHHQJZWWAEH-UHFFFAOYSA-N 0.000 description 1
- RSZMTXPFGDUHSE-UHFFFAOYSA-N 2-nitro-1-benzofuran Chemical compound C1=CC=C2OC([N+](=O)[O-])=CC2=C1 RSZMTXPFGDUHSE-UHFFFAOYSA-N 0.000 description 1
- UDAIGHZFMLGNDQ-UHFFFAOYSA-N 2-nitroquinoline Chemical compound C1=CC=CC2=NC([N+](=O)[O-])=CC=C21 UDAIGHZFMLGNDQ-UHFFFAOYSA-N 0.000 description 1
- BFOGZBLYCKTATH-UHFFFAOYSA-N 3-methyl-5-nitro-1-benzofuran-2-carboxylic acid Chemical compound C1=C([N+]([O-])=O)C=C2C(C)=C(C(O)=O)OC2=C1 BFOGZBLYCKTATH-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 101000632319 Homo sapiens Septin-7 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 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 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 102100027981 Septin-7 Human genes 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- HJPOKQICBCJGHE-UHFFFAOYSA-J [C+4].[Cl-].[Cl-].[Cl-].[Cl-] Chemical compound [C+4].[Cl-].[Cl-].[Cl-].[Cl-] HJPOKQICBCJGHE-UHFFFAOYSA-J 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- PXAJQJMDEXJWFB-UHFFFAOYSA-N acetone oxime Chemical compound CC(C)=NO PXAJQJMDEXJWFB-UHFFFAOYSA-N 0.000 description 1
- 230000036982 action potential Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- BGWMHFKCAUBYJJ-UHFFFAOYSA-N ethyl 2-chloroethanimidate;hydrochloride Chemical compound Cl.CCOC(=N)CCl BGWMHFKCAUBYJJ-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- NPJAJPXYAHTSQW-UHFFFAOYSA-N n-(4-nitrophenoxy)propan-2-imine Chemical compound CC(C)=NOC1=CC=C([N+]([O-])=O)C=C1 NPJAJPXYAHTSQW-UHFFFAOYSA-N 0.000 description 1
- MSZBIHITHNHHTL-UHFFFAOYSA-N n-[4-[2-(methylamino)ethyl]phenyl]methanesulfonamide Chemical compound CNCCC1=CC=C(NS(C)(=O)=O)C=C1 MSZBIHITHNHHTL-UHFFFAOYSA-N 0.000 description 1
- LMMFCDQGHJZZQP-UHFFFAOYSA-N n-[4-[2-[(5-amino-3-methyl-1-benzofuran-2-yl)methyl-methylamino]ethyl]phenyl]methanesulfonamide Chemical compound O1C2=CC=C(N)C=C2C(C)=C1CN(C)CCC1=CC=C(NS(C)(=O)=O)C=C1 LMMFCDQGHJZZQP-UHFFFAOYSA-N 0.000 description 1
- RSCCIURMNSFHOV-UHFFFAOYSA-N n-[4-[2-[(6-aminoquinolin-2-yl)methyl-ethylamino]ethyl]phenyl]methanesulfonamide Chemical compound C=1C=C2C=C(N)C=CC2=NC=1CN(CC)CCC1=CC=C(NS(C)(=O)=O)C=C1 RSCCIURMNSFHOV-UHFFFAOYSA-N 0.000 description 1
- UWUVSPJRQDDZQM-UHFFFAOYSA-N n-[4-[2-[[5-(methanesulfonamido)-1,3-benzoxazol-2-yl]methyl-methylamino]ethyl]phenyl]methanesulfonamide Chemical compound N=1C2=CC(NS(C)(=O)=O)=CC=C2OC=1CN(C)CCC1=CC=C(NS(C)(=O)=O)C=C1 UWUVSPJRQDDZQM-UHFFFAOYSA-N 0.000 description 1
- SZUFFRWWUDYVNS-UHFFFAOYSA-N n-[4-[2-[[5-(methanesulfonamido)-3-methyl-1-benzofuran-2-yl]methyl-methylamino]ethyl]phenyl]methanesulfonamide Chemical compound O1C2=CC=C(NS(C)(=O)=O)C=C2C(C)=C1CN(C)CCC1=CC=C(NS(C)(=O)=O)C=C1 SZUFFRWWUDYVNS-UHFFFAOYSA-N 0.000 description 1
- RQEVHUODEXVJGD-UHFFFAOYSA-N n-[4-[2-[[6-(methanesulfonamido)quinolin-2-yl]methyl-methylamino]ethyl]phenyl]methanesulfonamide Chemical compound C=1C=C2C=C(NS(C)(=O)=O)C=CC2=NC=1CN(C)CCC1=CC=C(NS(C)(=O)=O)C=C1 RQEVHUODEXVJGD-UHFFFAOYSA-N 0.000 description 1
- MGWZHRCWHGTNAQ-UHFFFAOYSA-N n-[4-[2-[benzyl(ethyl)amino]ethyl]phenyl]methanesulfonamide Chemical compound C=1C=CC=CC=1CN(CC)CCC1=CC=C(NS(C)(=O)=O)C=C1 MGWZHRCWHGTNAQ-UHFFFAOYSA-N 0.000 description 1
- DUGUPLLVLPHCSH-UHFFFAOYSA-N n-[4-[2-[ethyl-[(6-nitroquinolin-2-yl)methyl]amino]ethyl]phenyl]methanesulfonamide Chemical compound C=1C=C2C=C([N+]([O-])=O)C=CC2=NC=1CN(CC)CCC1=CC=C(NS(C)(=O)=O)C=C1 DUGUPLLVLPHCSH-UHFFFAOYSA-N 0.000 description 1
- SSSBLKUNQKLDNY-UHFFFAOYSA-N n-[4-[2-[methyl-[(3-methyl-5-nitro-1-benzofuran-2-yl)methyl]amino]ethyl]phenyl]methanesulfonamide Chemical compound O1C2=CC=C([N+]([O-])=O)C=C2C(C)=C1CN(C)CCC1=CC=C(NS(C)(=O)=O)C=C1 SSSBLKUNQKLDNY-UHFFFAOYSA-N 0.000 description 1
- HVAAHUDGWQAAOJ-UHFFFAOYSA-N n-benzylethanamine Chemical compound CCNCC1=CC=CC=C1 HVAAHUDGWQAAOJ-UHFFFAOYSA-N 0.000 description 1
- PQLBGKILBLRBGW-UHFFFAOYSA-N n-methyl-2-(4-nitrophenyl)-n-[(6-nitroquinolin-2-yl)methyl]ethanamine Chemical compound C=1C=C2C=C([N+]([O-])=O)C=CC2=NC=1CN(C)CCC1=CC=C([N+]([O-])=O)C=C1 PQLBGKILBLRBGW-UHFFFAOYSA-N 0.000 description 1
- QYFHKUGJAQWSGZ-UHFFFAOYSA-N n-methyl-n-[(5-nitro-1,3-benzoxazol-2-yl)methyl]-2-(4-nitrophenyl)ethanamine Chemical compound N=1C2=CC([N+]([O-])=O)=CC=C2OC=1CN(C)CCC1=CC=C([N+]([O-])=O)C=C1 QYFHKUGJAQWSGZ-UHFFFAOYSA-N 0.000 description 1
- GPCHBORISGREGL-UHFFFAOYSA-N n-methyl-n-[(6-nitro-1,3-benzoxazol-2-yl)methyl]-2-(4-nitrophenyl)ethanamine Chemical compound N=1C2=CC=C([N+]([O-])=O)C=C2OC=1CN(C)CCC1=CC=C([N+]([O-])=O)C=C1 GPCHBORISGREGL-UHFFFAOYSA-N 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000003540 papillary muscle Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000009090 positive inotropic effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 210000005241 right ventricle Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB878702789A GB8702789D0 (en) | 1987-02-07 | 1987-02-07 | Antiarrhythmic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PT86702A PT86702A (pt) | 1988-03-01 |
| PT86702B true PT86702B (pt) | 1992-04-30 |
Family
ID=10611890
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT86702A PT86702B (pt) | 1987-02-07 | 1988-02-05 | Processo para a prepapacao de metano-sulfonamido-fenetilaminas substituidas |
Country Status (6)
| Country | Link |
|---|---|
| AT (1) | ATE49598T1 (de) |
| DE (1) | DE3860028D1 (de) |
| GB (1) | GB8702789D0 (de) |
| GR (1) | GR3000315T3 (de) |
| PT (1) | PT86702B (de) |
| ZA (1) | ZA883639B (de) |
-
1987
- 1987-02-07 GB GB878702789A patent/GB8702789D0/en active Pending
-
1988
- 1988-02-05 DE DE8888300962T patent/DE3860028D1/de not_active Expired - Lifetime
- 1988-02-05 AT AT88300962T patent/ATE49598T1/de not_active IP Right Cessation
- 1988-02-05 PT PT86702A patent/PT86702B/pt not_active IP Right Cessation
- 1988-05-23 ZA ZA883639A patent/ZA883639B/xx unknown
-
1990
- 1990-01-19 GR GR90400034T patent/GR3000315T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PT86702A (pt) | 1988-03-01 |
| ZA883639B (en) | 1990-02-28 |
| DE3860028D1 (de) | 1990-02-22 |
| ATE49598T1 (de) | 1990-02-15 |
| GB8702789D0 (en) | 1987-03-11 |
| GR3000315T3 (en) | 1991-06-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0281254B1 (de) | Antiarrhythmische Mittel | |
| US5006561A (en) | Indane sulfonamide anti-arrhythmic agents and use | |
| JP2653850B2 (ja) | スルホンアミド抗不整脈剤 | |
| PT87048B (pt) | Processo para a preparacao de agentes antiarritmicos de benzazepino-sulfonamidas | |
| JPH0567150B2 (de) | ||
| PT87362B (pt) | Processo para a preparacao de derivados de fenil-piperidina uteis como agentes anti-arritmicos | |
| US5130334A (en) | Indane sulfonamide anti-arrhythmic agents | |
| EP0285284B1 (de) | N-phényléthylaminoalkyl-Benzamide als antiarrhythmische Mittel | |
| EP0285323B1 (de) | Antiarrhythmische Mittel | |
| PT86702B (pt) | Processo para a prepapacao de metano-sulfonamido-fenetilaminas substituidas | |
| IE913372A1 (en) | Antiarrhythmic agents | |
| US4224335A (en) | Tetrahydrocarbazoles and their use | |
| KR910004674B1 (ko) | 부정맥치료제 | |
| HU201002B (en) | Process for production of derivatives of indan sulphamid and medical compositions containing them | |
| PL158277B1 (en) | Method of obtaining novel sulfonamides | |
| NO171635B (no) | Analogifremgangsmaate til fremstilling av et alkysulfonamidofenylalkylamin som er n-substituert over en metylenkjedemed en heterocyklisk gruppe | |
| DD281599A5 (de) | Verfahren zur herstellung neuer sulfonamide | |
| CS272789B2 (en) | Method of sulfonamidoindane production | |
| HU201743B (en) | Process for producing sulfonamide derivatives with antiarrythmic effect and pharmaceutical compositions comprising same | |
| IL86458A (en) | Heterocyclic sulfonamido phenethylamine derivatives, their preparation and pharmaceutifal compositions containing them and intermediates therefor | |
| PL158278B1 (en) | Method of obtaining novel derivatives of indanosulfonamides | |
| CS271489B2 (en) | Method of alkylsulphonamidophenethylamines' sulphonamidoderivatives production |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG3A | Patent granted, date of granting |
Effective date: 19911016 |
|
| MM3A | Annulment or lapse |
Free format text: LAPSE DUE TO NON-PAYMENT OF FEES Effective date: 20040430 |