SK285259B6 - Deriváty 3-amino-3-arylpropan-1-olu, spôsob ich výroby, liečivá tieto látky obsahujúce a ich použitie - Google Patents
Deriváty 3-amino-3-arylpropan-1-olu, spôsob ich výroby, liečivá tieto látky obsahujúce a ich použitie Download PDFInfo
- Publication number
- SK285259B6 SK285259B6 SK496-2000A SK4962000A SK285259B6 SK 285259 B6 SK285259 B6 SK 285259B6 SK 4962000 A SK4962000 A SK 4962000A SK 285259 B6 SK285259 B6 SK 285259B6
- Authority
- SK
- Slovakia
- Prior art keywords
- cyclohexanol
- corresponding hydrochloride
- dimethylaminophenylmethyl
- hydrochloride
- mmol
- Prior art date
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- 239000003814 drug Substances 0.000 title claims abstract description 43
- 238000000034 method Methods 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 286
- 239000000203 mixture Substances 0.000 claims description 103
- 150000001875 compounds Chemical class 0.000 claims description 85
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 80
- -1 OR 14 Chemical group 0.000 claims description 51
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
- 125000003118 aryl group Chemical group 0.000 claims description 31
- 125000004432 carbon atom Chemical group C* 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 125000004122 cyclic group Chemical group 0.000 claims description 16
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 14
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 229910052717 sulfur Chemical group 0.000 claims description 11
- 208000002193 Pain Diseases 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 230000036407 pain Effects 0.000 claims description 7
- 229930192474 thiophene Natural products 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- 150000003577 thiophenes Chemical class 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- MEWHOURHDIYFRU-UHFFFAOYSA-N 1-benzyl-2-[dimethylamino(phenyl)methyl]cyclohexan-1-ol Chemical compound C=1C=CC=CC=1C(N(C)C)C1CCCCC1(O)CC1=CC=CC=C1 MEWHOURHDIYFRU-UHFFFAOYSA-N 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 150000007513 acids Chemical class 0.000 claims description 5
- 239000013543 active substance Substances 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Chemical group 0.000 claims description 5
- 239000011593 sulfur Chemical group 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 206010012735 Diarrhoea Diseases 0.000 claims description 4
- 208000003251 Pruritus Diseases 0.000 claims description 4
- 206010046543 Urinary incontinence Diseases 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 230000003474 anti-emetic effect Effects 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000003589 local anesthetic agent Substances 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 230000001777 nootropic effect Effects 0.000 claims description 4
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 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
- 208000000094 Chronic Pain Diseases 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 3
- 150000002902 organometallic compounds Chemical class 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- QRNBGIFHSHVVQJ-UHFFFAOYSA-N 1-[(4-tert-butylphenyl)methyl]-2-[dimethylamino(thiophen-2-yl)methyl]cyclohexan-1-ol Chemical compound C=1C=CSC=1C(N(C)C)C1CCCCC1(O)CC1=CC=C(C(C)(C)C)C=C1 QRNBGIFHSHVVQJ-UHFFFAOYSA-N 0.000 claims description 2
- OFKSZYAAGJVQLH-UHFFFAOYSA-N 1-benzyl-2-[phenyl(piperidin-1-yl)methyl]cyclohexan-1-ol Chemical compound C1CCCC(C(N2CCCCC2)C=2C=CC=CC=2)C1(O)CC1=CC=CC=C1 OFKSZYAAGJVQLH-UHFFFAOYSA-N 0.000 claims description 2
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 2
- NYVZPFREDHUXAL-UHFFFAOYSA-N 2-[dimethylamino(phenyl)methyl]-1-(4-methylphenyl)cyclohexan-1-ol Chemical compound C=1C=CC=CC=1C(N(C)C)C1CCCCC1(O)C1=CC=C(C)C=C1 NYVZPFREDHUXAL-UHFFFAOYSA-N 0.000 claims description 2
- IBYVBOVXUPQBCV-UHFFFAOYSA-N 2-[dimethylamino-(2-methylphenyl)methyl]-1-phenylcyclohexan-1-ol Chemical compound C=1C=CC=C(C)C=1C(N(C)C)C1CCCCC1(O)C1=CC=CC=C1 IBYVBOVXUPQBCV-UHFFFAOYSA-N 0.000 claims description 2
- 208000020401 Depressive disease Diseases 0.000 claims description 2
- 230000003288 anthiarrhythmic effect Effects 0.000 claims description 2
- 150000005840 aryl radicals Chemical class 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000002346 iodo group Chemical group I* 0.000 claims description 2
- 208000004296 neuralgia Diseases 0.000 claims description 2
- 208000021722 neuropathic pain Diseases 0.000 claims description 2
- 206010013663 drug dependence Diseases 0.000 claims 2
- 230000002708 enhancing effect Effects 0.000 claims 2
- 208000011117 substance-related disease Diseases 0.000 claims 2
- RLHUBQPQIVZANW-UHFFFAOYSA-N 1-[(2,5-difluorophenyl)methyl]-2-[dimethylamino(phenyl)methyl]cyclohexan-1-ol Chemical compound C=1C=CC=CC=1C(N(C)C)C1CCCCC1(O)CC1=CC(F)=CC=C1F RLHUBQPQIVZANW-UHFFFAOYSA-N 0.000 claims 1
- IPTJOFLYRYUGSF-UHFFFAOYSA-N 1-benzyl-2-[dimethylamino-(2-methylphenyl)methyl]cyclohexan-1-ol Chemical compound C=1C=CC=C(C)C=1C(N(C)C)C1CCCCC1(O)CC1=CC=CC=C1 IPTJOFLYRYUGSF-UHFFFAOYSA-N 0.000 claims 1
- 208000007848 Alcoholism Diseases 0.000 claims 1
- 206010061218 Inflammation Diseases 0.000 claims 1
- 201000007930 alcohol dependence Diseases 0.000 claims 1
- 230000003444 anaesthetic effect Effects 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 884
- 229960004132 diethyl ether Drugs 0.000 description 294
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 280
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 278
- 238000001816 cooling Methods 0.000 description 176
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 175
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 159
- 239000000284 extract Substances 0.000 description 144
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 136
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 133
- 229910052938 sodium sulfate Inorganic materials 0.000 description 133
- 235000011152 sodium sulphate Nutrition 0.000 description 133
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 128
- 239000000243 solution Substances 0.000 description 124
- 239000011541 reaction mixture Substances 0.000 description 114
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 62
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 55
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 51
- 235000011114 ammonium hydroxide Nutrition 0.000 description 51
- RLAIUHMFJDHPGV-UHFFFAOYSA-N 2-[dimethylamino(phenyl)methyl]cyclohexan-1-one Chemical compound C=1C=CC=CC=1C(N(C)C)C1CCCCC1=O RLAIUHMFJDHPGV-UHFFFAOYSA-N 0.000 description 45
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 45
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 238000003756 stirring Methods 0.000 description 33
- 230000027455 binding Effects 0.000 description 24
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 18
- KTZNVZJECQAMBV-UHFFFAOYSA-N 1-(cyclohexen-1-yl)pyrrolidine Chemical compound C1CCCN1C1=CCCCC1 KTZNVZJECQAMBV-UHFFFAOYSA-N 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 15
- 235000009518 sodium iodide Nutrition 0.000 description 15
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 14
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 14
- 238000010828 elution Methods 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 10
- 229940079593 drug Drugs 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- SCEZYJKGDJPHQO-UHFFFAOYSA-M magnesium;methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=CC=C1 SCEZYJKGDJPHQO-UHFFFAOYSA-M 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- ACSYTDOIVOCDTL-UHFFFAOYSA-N 4-[dimethylamino-[2-hydroxy-2-[4-(trifluoromethyl)phenyl]cyclohexyl]methyl]benzonitrile hydrochloride Chemical compound Cl.CN(C)C(C1CCCCC1(O)c1ccc(cc1)C(F)(F)F)c1ccc(cc1)C#N ACSYTDOIVOCDTL-UHFFFAOYSA-N 0.000 description 7
- RREANTFLPGEWEN-MBLPBCRHSA-N 7-[4-[[(3z)-3-[4-amino-5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidin-2-yl]imino-5-fluoro-2-oxoindol-1-yl]methyl]piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(\N=C/3C4=CC(F)=CC=C4N(CN4CCN(CC4)C=4C(=CC=5C(=O)C(C(O)=O)=CN(C=5C=4)C4CC4)F)C\3=O)=NC=2)N)=C1 RREANTFLPGEWEN-MBLPBCRHSA-N 0.000 description 7
- 235000011089 carbon dioxide Nutrition 0.000 description 7
- 229960004166 diltiazem Drugs 0.000 description 7
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 150000002081 enamines Chemical class 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- ISNYUQWBWALXEY-OMIQOYQYSA-N tsg6xhx09r Chemical compound O([C@@H](C)C=1[C@@]23CN(C)CCO[C@]3(C3=CC[C@H]4[C@]5(C)CC[C@@](C4)(O)O[C@@]53[C@H](O)C2)CC=1)C(=O)C=1C(C)=CNC=1C ISNYUQWBWALXEY-OMIQOYQYSA-N 0.000 description 6
- 229960001722 verapamil Drugs 0.000 description 6
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 5
- HXGMBPVFIKAXKE-UHFFFAOYSA-N 2-[(2-chlorophenyl)-(dimethylamino)methyl]cyclohexan-1-one Chemical compound C=1C=CC=C(Cl)C=1C(N(C)C)C1CCCCC1=O HXGMBPVFIKAXKE-UHFFFAOYSA-N 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 125000005037 alkyl phenyl group Chemical group 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- MMMPGIMWFARYOW-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)-2-[dimethylamino(phenyl)methyl]cyclohexan-1-ol Chemical compound C=1C=CC=CC=1C(N(C)C)C1CCCCC1(O)C1=CC=C(Cl)C(Cl)=C1 MMMPGIMWFARYOW-UHFFFAOYSA-N 0.000 description 4
- XGASTRVQNVVYIZ-UHFFFAOYSA-N 1-(chloromethyl)-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(CCl)=C1 XGASTRVQNVVYIZ-UHFFFAOYSA-N 0.000 description 4
- WAXIFMGAKWIFDQ-UHFFFAOYSA-N 1-tert-butyl-4-(chloromethyl)benzene Chemical compound CC(C)(C)C1=CC=C(CCl)C=C1 WAXIFMGAKWIFDQ-UHFFFAOYSA-N 0.000 description 4
- UZNZKWUYJNRLOO-UHFFFAOYSA-N 2-[(3,4-dichlorophenyl)-(dimethylamino)methyl]cyclohexan-1-one Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(N(C)C)C1CCCCC1=O UZNZKWUYJNRLOO-UHFFFAOYSA-N 0.000 description 4
- VFJLUDUYKMCIPD-UHFFFAOYSA-N 2-[dimethylamino(phenyl)methyl]-1-(2-methylsulfanylphenyl)cyclohexan-1-ol hydrochloride Chemical compound Cl.CSc1ccccc1C1(O)CCCCC1C(N(C)C)c1ccccc1 VFJLUDUYKMCIPD-UHFFFAOYSA-N 0.000 description 4
- VRWNXXQLKCTNTD-UHFFFAOYSA-N 2-[dimethylamino(thiophen-2-yl)methyl]cyclohexan-1-one Chemical compound C=1C=CSC=1C(N(C)C)C1CCCCC1=O VRWNXXQLKCTNTD-UHFFFAOYSA-N 0.000 description 4
- SDTRTSWQUIXSFS-UHFFFAOYSA-N 2-[dimethylamino-(3-methoxyphenyl)methyl]cyclohexan-1-one Chemical compound COC1=CC=CC(C(C2C(CCCC2)=O)N(C)C)=C1 SDTRTSWQUIXSFS-UHFFFAOYSA-N 0.000 description 4
- PWKUZOYYUQSZBW-UHFFFAOYSA-N 2-[dimethylamino-(3-phenoxyphenyl)methyl]cyclohexan-1-one Chemical compound C=1C=CC(OC=2C=CC=CC=2)=CC=1C(N(C)C)C1CCCCC1=O PWKUZOYYUQSZBW-UHFFFAOYSA-N 0.000 description 4
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 4
- 239000012346 acetyl chloride Substances 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 4
- HFNCOTSLOKKPHU-UHFFFAOYSA-N cyclohexanol;hydrochloride Chemical compound Cl.OC1CCCCC1 HFNCOTSLOKKPHU-UHFFFAOYSA-N 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- OUTILEHLSPAZIN-UHFFFAOYSA-M magnesium;ethylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]CC1=CC=CC=C1 OUTILEHLSPAZIN-UHFFFAOYSA-M 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
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- 229960002748 norepinephrine Drugs 0.000 description 1
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- OCDANELISROGHW-UHFFFAOYSA-N phenylmethanimine;hydrochloride Chemical compound Cl.N=CC1=CC=CC=C1 OCDANELISROGHW-UHFFFAOYSA-N 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
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- 150000001420 substituted heterocyclic compounds Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
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- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
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- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
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- FVECELJHCSPHKY-JLSHOZRYSA-N veratridine Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)O[C@@H]1[C@@]2(O)O[C@]34C[C@@]5(O)[C@H](CN6[C@@H](CC[C@H](C)C6)[C@@]6(C)O)[C@]6(O)[C@@H](O)C[C@@]5(O)[C@@H]4CC[C@H]2[C@]3(C)CC1 FVECELJHCSPHKY-JLSHOZRYSA-N 0.000 description 1
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Classifications
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- C07C255/58—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
- C07C255/59—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
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- C07C323/31—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
- C07C323/32—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton having at least one of the nitrogen atoms bound to an acyclic carbon atom of the carbon skeleton
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- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19915601A DE19915601A1 (de) | 1999-04-07 | 1999-04-07 | 3-Amino-3-arylpropan-1-ol-Derivate, deren Herstellung und Verwendung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK4962000A3 SK4962000A3 (en) | 2000-10-09 |
| SK285259B6 true SK285259B6 (sk) | 2006-10-05 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK496-2000A SK285259B6 (sk) | 1999-04-07 | 2000-04-06 | Deriváty 3-amino-3-arylpropan-1-olu, spôsob ich výroby, liečivá tieto látky obsahujúce a ich použitie |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US6410790B1 (cs) |
| EP (1) | EP1043307B1 (cs) |
| JP (1) | JP2000327642A (cs) |
| KR (1) | KR20000071575A (cs) |
| CN (1) | CN1183098C (cs) |
| AR (1) | AR033941A1 (cs) |
| AT (1) | ATE242197T1 (cs) |
| BR (1) | BR0008682A (cs) |
| CA (1) | CA2304127A1 (cs) |
| CO (1) | CO5160346A1 (cs) |
| CZ (1) | CZ299556B6 (cs) |
| DE (2) | DE19915601A1 (cs) |
| DK (1) | DK1043307T3 (cs) |
| ES (1) | ES2200740T3 (cs) |
| HU (1) | HUP0001396A2 (cs) |
| IL (1) | IL135451A0 (cs) |
| MY (1) | MY133112A (cs) |
| NO (1) | NO20001781L (cs) |
| NZ (1) | NZ503396A (cs) |
| PE (1) | PE20001648A1 (cs) |
| PL (1) | PL200272B1 (cs) |
| PT (1) | PT1043307E (cs) |
| SI (1) | SI1043307T1 (cs) |
| SK (1) | SK285259B6 (cs) |
| ZA (1) | ZA200001746B (cs) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4426245A1 (de) | 1994-07-23 | 1996-02-22 | Gruenenthal Gmbh | 1-Phenyl-3-dimethylamino-propanverbindungen mit pharmakologischer Wirkung |
| DE19915602A1 (de) * | 1999-04-07 | 2000-10-19 | Gruenenthal Gmbh | 3-Amino-4-arylpropan-1-ol-Derivate, deren Herstellung und Verwendung |
| DE19963175A1 (de) * | 1999-12-27 | 2001-07-12 | Gruenenthal Gmbh | Verwendung von substituierten 4-Amino-1-phenylbutan-2-ol-Verbindungen als Arzneimittel |
| DE10025238A1 (de) * | 2000-05-22 | 2001-11-29 | Gruenenthal Gmbh | Verwendung substituierter 1-Amino-5-phenylpentan-3-ol- und/oder 1-Amino-6-phenylhexan-3-ol- Verbindungen als Arzneimittel |
| DE10049481A1 (de) * | 2000-09-29 | 2002-05-02 | Gruenenthal Gmbh | Substituierte C-Cyclohexylmethylamin-Derivate |
| DE10049483A1 (de) * | 2000-09-29 | 2002-05-02 | Gruenenthal Gmbh | Substituierte 1-Aminobutan-3-ol-Derivate |
| DE10108307A1 (de) * | 2001-02-21 | 2002-08-29 | Gruenenthal Gmbh | Substituierte Propan-1,3-diamin-Derivate |
| DE10132747A1 (de) * | 2001-07-05 | 2003-01-23 | Gruenenthal Gmbh | Substituierte 1-Aryl-but-3-enylamin- und 1-Aryl-but-2-enylaminverbindungen |
| DE10164581A1 (de) * | 2001-12-14 | 2003-06-26 | Gruenenthal Gmbh | Substituierte Aminoalkohole |
| DE10161644A1 (de) * | 2001-12-14 | 2003-06-26 | Gruenenthal Gmbh | N,N'-disubstituierte Piperazin-Verbindungen |
| DE10161809A1 (de) * | 2001-12-14 | 2003-06-26 | Gruenenthal Gmbh | Arzneimittel enthaltend N,N'-disubstituierte Piperazin-Verbindungen |
| DE10161818A1 (de) * | 2001-12-14 | 2003-06-26 | Gruenenthal Gmbh | Substituierte 1,5-Diaminopentan-3-ol-Verbindungen |
| DE10213051B4 (de) * | 2002-03-23 | 2013-03-07 | Grünenthal GmbH | Substituierte 4-Aminocyclohexanole |
| DE102004034619A1 (de) * | 2004-07-16 | 2006-02-23 | Grünenthal GmbH | Substituierte Aminoverbindungen als 5-HT/NA Uptakehemmer |
| DE102005061428A1 (de) * | 2005-12-22 | 2007-08-16 | Grünenthal GmbH | Substituierte Cyclohexylmethyl-Derivate |
| AU2015202379B2 (en) * | 2007-05-31 | 2016-10-13 | Sunovion Pharmaceuticals Inc. | Phenyl substituted cycloalkylamines as monoamine reuptake inhibitors |
| NZ580429A (en) * | 2007-05-31 | 2012-04-27 | Sepracor Inc | Phenyl substituted cycloalkylamines as monoamine reuptake inhibitors |
| CN118108610B (zh) * | 2024-04-30 | 2025-01-10 | 山东新华制药股份有限公司 | 盐酸去甲曲马多的制备方法 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB815217A (en) * | 1957-12-03 | 1959-06-17 | Bayer Ag | 1-o-chlorophenyl-1-phenyl-3-(dimethylamino)-propan-1-ol and its salts and therapeuticcompositions containing them |
| AT28628B (de) * | 1905-11-04 | 1907-06-10 | Neue Photographische Ges Ag | Verwandlungsbilder, bei welchen die Umwandlung des Bildes durch Lichtwirkung hervorgerufen wird. |
| GB657301A (en) * | 1948-02-25 | 1951-09-19 | Wellcome Found | Improvements in and relating to the preparation of substituted amino-alcohols and derivatives thereof |
| GB811659A (en) * | 1955-07-05 | 1959-04-08 | Bayer Ag | Process for producing derivatives of 1-aryl-3-amino propanol-1 |
| US4017637A (en) | 1973-03-26 | 1977-04-12 | American Home Products Corporation | Benzylamine analgesics |
| US4155935A (en) * | 1973-03-26 | 1979-05-22 | American Home Products Corporation | Benzylamine analgesics |
| US4366172A (en) * | 1977-09-29 | 1982-12-28 | The Upjohn Company | 4-Amino-cyclohexanols, their pharmaceutical compositions and methods of use |
| AU566673B2 (en) * | 1983-09-15 | 1987-10-29 | F. Hoffmann-La Roche Ag | Phenethylamine derivatives |
| JPS60246349A (ja) * | 1984-05-22 | 1985-12-06 | Tozaburo Kurihara | 2−置換−1−ジメチルアミノメチル−シクロヘキサン及びその製造法 |
| JPH08198823A (ja) * | 1995-01-23 | 1996-08-06 | Nippon Soda Co Ltd | 3−アミノ−3−アリール−1−プロパノール誘導体の製造方法 |
| DE19915602A1 (de) * | 1999-04-07 | 2000-10-19 | Gruenenthal Gmbh | 3-Amino-4-arylpropan-1-ol-Derivate, deren Herstellung und Verwendung |
| CZ20001251A3 (cs) * | 2000-04-06 | 2000-11-15 | Grünenthal GmbH | Deriváty 3-amino-3-aryIpropan-l-olu, způsob jejich výroby, léčiva tyto látky obsahující a jejich použití |
-
1999
- 1999-04-07 DE DE19915601A patent/DE19915601A1/de not_active Withdrawn
-
2000
- 2000-03-08 DE DE50002417T patent/DE50002417D1/de not_active Expired - Lifetime
- 2000-03-08 AT AT00104477T patent/ATE242197T1/de not_active IP Right Cessation
- 2000-03-08 DK DK00104477T patent/DK1043307T3/da active
- 2000-03-08 ES ES00104477T patent/ES2200740T3/es not_active Expired - Lifetime
- 2000-03-08 PT PT00104477T patent/PT1043307E/pt unknown
- 2000-03-08 SI SI200030171T patent/SI1043307T1/xx unknown
- 2000-03-08 EP EP00104477A patent/EP1043307B1/de not_active Expired - Lifetime
- 2000-03-14 NZ NZ503396A patent/NZ503396A/xx unknown
- 2000-03-31 MY MYPI20001313A patent/MY133112A/en unknown
- 2000-04-03 AR ARP000101520A patent/AR033941A1/es not_active Application Discontinuation
- 2000-04-04 IL IL13545100A patent/IL135451A0/xx unknown
- 2000-04-04 PE PE2000000292A patent/PE20001648A1/es not_active Application Discontinuation
- 2000-04-05 CA CA002304127A patent/CA2304127A1/en not_active Abandoned
- 2000-04-05 BR BR0008682-7A patent/BR0008682A/pt not_active IP Right Cessation
- 2000-04-05 HU HU0001396A patent/HUP0001396A2/hu unknown
- 2000-04-05 CO CO00024762A patent/CO5160346A1/es unknown
- 2000-04-06 PL PL339486A patent/PL200272B1/pl not_active IP Right Cessation
- 2000-04-06 CZ CZ20001250A patent/CZ299556B6/cs not_active IP Right Cessation
- 2000-04-06 NO NO20001781A patent/NO20001781L/no not_active Application Discontinuation
- 2000-04-06 SK SK496-2000A patent/SK285259B6/sk not_active IP Right Cessation
- 2000-04-06 ZA ZA200001746A patent/ZA200001746B/xx unknown
- 2000-04-06 KR KR1020000017910A patent/KR20000071575A/ko not_active Withdrawn
- 2000-04-06 JP JP2000105250A patent/JP2000327642A/ja not_active Withdrawn
- 2000-04-06 CN CNB001049798A patent/CN1183098C/zh not_active Expired - Fee Related
- 2000-04-07 US US09/545,371 patent/US6410790B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| KR20000071575A (ko) | 2000-11-25 |
| PL200272B1 (pl) | 2008-12-31 |
| ES2200740T3 (es) | 2004-03-16 |
| BR0008682A (pt) | 2002-02-26 |
| JP2000327642A (ja) | 2000-11-28 |
| NO20001781D0 (no) | 2000-04-06 |
| DE50002417D1 (de) | 2003-07-10 |
| HU0001396D0 (en) | 2000-06-28 |
| MY133112A (en) | 2007-10-31 |
| PE20001648A1 (es) | 2001-01-20 |
| CZ299556B6 (cs) | 2008-09-03 |
| HK1031725A1 (en) | 2001-06-22 |
| US6410790B1 (en) | 2002-06-25 |
| ATE242197T1 (de) | 2003-06-15 |
| EP1043307A3 (de) | 2001-07-18 |
| HUP0001396A2 (hu) | 2002-04-29 |
| NO20001781L (no) | 2000-10-09 |
| EP1043307A2 (de) | 2000-10-11 |
| NZ503396A (en) | 2000-11-24 |
| AR033941A1 (es) | 2004-01-21 |
| CN1270162A (zh) | 2000-10-18 |
| DE19915601A1 (de) | 2000-10-19 |
| ZA200001746B (en) | 2000-12-06 |
| IL135451A0 (en) | 2001-05-20 |
| PT1043307E (pt) | 2003-10-31 |
| SK4962000A3 (en) | 2000-10-09 |
| EP1043307B1 (de) | 2003-06-04 |
| DK1043307T3 (da) | 2003-09-22 |
| PL339486A1 (en) | 2000-10-09 |
| CA2304127A1 (en) | 2000-10-07 |
| CZ20001250A3 (cs) | 2000-11-15 |
| SI1043307T1 (en) | 2003-12-31 |
| CN1183098C (zh) | 2005-01-05 |
| CO5160346A1 (es) | 2002-05-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed due to non-payment of maintenance fees |
Effective date: 20100406 |