PT85547B - Processo de preparacao de composicao farmaceuticas a base de derivados de 2-mercapto-imidazol e de preparacao destes derivados - Google Patents
Processo de preparacao de composicao farmaceuticas a base de derivados de 2-mercapto-imidazol e de preparacao destes derivados Download PDFInfo
- Publication number
- PT85547B PT85547B PT85547A PT8554787A PT85547B PT 85547 B PT85547 B PT 85547B PT 85547 A PT85547 A PT 85547A PT 8554787 A PT8554787 A PT 8554787A PT 85547 B PT85547 B PT 85547B
- Authority
- PT
- Portugal
- Prior art keywords
- mole
- alkyl
- compounds
- mercaptoimidazole
- acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 24
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- OXFSTTJBVAAALW-UHFFFAOYSA-N 1,3-dihydroimidazole-2-thione Chemical class SC1=NC=CN1 OXFSTTJBVAAALW-UHFFFAOYSA-N 0.000 title description 10
- 238000002360 preparation method Methods 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 89
- 125000000217 alkyl group Chemical group 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 21
- -1 1- (3,5-difluor-4-methoxybenzyl) aminoacetaldehyde-dimethylacetal Chemical compound 0.000 claims description 17
- 230000008569 process Effects 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 7
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 4
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- IRYFWPMPRFLYGC-UHFFFAOYSA-N 3-[(3-fluoro-4-methoxyphenyl)methyl]-1h-imidazole-2-thione Chemical compound C1=C(F)C(OC)=CC=C1CN1C(S)=NC=C1 IRYFWPMPRFLYGC-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000011049 filling Methods 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- DERQGGRDVHGMPS-UHFFFAOYSA-N 3-(3-fluoro-4-methoxyphenyl)-2,2-dimethoxypropan-1-amine Chemical compound COC1=CC=C(CC(CN)(OC)OC)C=C1F DERQGGRDVHGMPS-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 22
- 239000003112 inhibitor Substances 0.000 abstract description 18
- 230000003389 potentiating effect Effects 0.000 abstract description 6
- 241000124008 Mammalia Species 0.000 abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 96
- 235000019441 ethanol Nutrition 0.000 description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 239000000243 solution Substances 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- 239000000203 mixture Substances 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 239000013078 crystal Substances 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- HJKLEAOXCZIMPI-UHFFFAOYSA-N 2,2-diethoxyethanamine Chemical compound CCOC(CN)OCC HJKLEAOXCZIMPI-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- 125000001309 chloro group Chemical group Cl* 0.000 description 12
- DGMPVYSXXIOGJY-UHFFFAOYSA-N Fusaric acid Chemical class CCCCC1=CC=C(C(O)=O)N=C1 DGMPVYSXXIOGJY-UHFFFAOYSA-N 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 10
- 229960002748 norepinephrine Drugs 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000001953 recrystallisation Methods 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000002934 diuretic Substances 0.000 description 8
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 229940030606 diuretics Drugs 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 206010020772 Hypertension Diseases 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 229940116357 potassium thiocyanate Drugs 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000002220 antihypertensive agent Substances 0.000 description 4
- 150000003935 benzaldehydes Chemical class 0.000 description 4
- 230000003177 cardiotonic effect Effects 0.000 description 4
- 150000003943 catecholamines Chemical class 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 3
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- 235000021355 Stearic acid Nutrition 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- NHOWLEZFTHYCTP-UHFFFAOYSA-N benzylhydrazine Chemical compound NNCC1=CC=CC=C1 NHOWLEZFTHYCTP-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 230000001631 hypertensive effect Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
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- 238000012360 testing method Methods 0.000 description 3
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 3
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- QHGUCRYDKWKLMG-QMMMGPOBSA-N (R)-octopamine Chemical compound NC[C@H](O)C1=CC=C(O)C=C1 QHGUCRYDKWKLMG-QMMMGPOBSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- CASRSOJWLARCRX-UHFFFAOYSA-N 3,5-dichlorobenzaldehyde Chemical compound ClC1=CC(Cl)=CC(C=O)=C1 CASRSOJWLARCRX-UHFFFAOYSA-N 0.000 description 2
- KBSLGHDKSCGXKQ-UHFFFAOYSA-N 3,5-difluoro-4-methoxybenzaldehyde Chemical compound COC1=C(F)C=C(C=O)C=C1F KBSLGHDKSCGXKQ-UHFFFAOYSA-N 0.000 description 2
- ASOFZHSTJHGQDT-UHFFFAOYSA-N 3,5-difluorobenzaldehyde Chemical compound FC1=CC(F)=CC(C=O)=C1 ASOFZHSTJHGQDT-UHFFFAOYSA-N 0.000 description 2
- GJSMIWZLHQYITP-UHFFFAOYSA-N 3-(3,5-dichlorophenyl)propanal Chemical compound ClC1=CC(Cl)=CC(CCC=O)=C1 GJSMIWZLHQYITP-UHFFFAOYSA-N 0.000 description 2
- LIEBCNQPMNARMP-UHFFFAOYSA-N 3-(4-methoxyphenyl)-1h-imidazole-2-thione Chemical compound C1=CC(OC)=CC=C1N1C(=S)NC=C1 LIEBCNQPMNARMP-UHFFFAOYSA-N 0.000 description 2
- JGGJPPRXUFKTAU-UHFFFAOYSA-N 3-[(3,5-difluoro-4-methoxyphenyl)methyl]-1h-imidazole-2-thione Chemical compound C1=C(F)C(OC)=C(F)C=C1CN1C(S)=NC=C1 JGGJPPRXUFKTAU-UHFFFAOYSA-N 0.000 description 2
- ZWZUDVZRZUZMPW-UHFFFAOYSA-N 3-[(3-bromo-4-methoxyphenyl)methyl]-1h-imidazole-2-thione Chemical compound C1=C(Br)C(OC)=CC=C1CN1C(S)=NC=C1 ZWZUDVZRZUZMPW-UHFFFAOYSA-N 0.000 description 2
- MKYOHTKSEDVAKU-UHFFFAOYSA-N 3-[(4-methoxyphenyl)methyl]-1h-imidazole-2-thione Chemical compound C1=CC(OC)=CC=C1CN1C(S)=NC=C1 MKYOHTKSEDVAKU-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
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- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
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- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 2
- PWZWGXSYAYXIND-UHFFFAOYSA-N n-[(3,5-difluoro-4-methoxyphenyl)methyl]-2,2-dimethoxyethanamine Chemical compound COC(OC)CNCC1=CC(F)=C(OC)C(F)=C1 PWZWGXSYAYXIND-UHFFFAOYSA-N 0.000 description 2
- WMMDEDRIYRHULI-UHFFFAOYSA-N n-[(3-bromo-4-methoxyphenyl)methyl]-2,2-diethoxyethanamine Chemical compound CCOC(OCC)CNCC1=CC=C(OC)C(Br)=C1 WMMDEDRIYRHULI-UHFFFAOYSA-N 0.000 description 2
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- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000563 toxic property Toxicity 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229960003732 tyramine Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/84—Sulfur atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Enzymes And Modification Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US89816586A | 1986-08-18 | 1986-08-18 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PT85547A PT85547A (pt) | 1988-08-17 |
| PT85547B true PT85547B (pt) | 1995-03-01 |
Family
ID=25409053
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT85547A PT85547B (pt) | 1986-08-18 | 1987-08-17 | Processo de preparacao de composicao farmaceuticas a base de derivados de 2-mercapto-imidazol e de preparacao destes derivados |
Country Status (15)
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4835154A (en) * | 1987-06-01 | 1989-05-30 | Smithkline Beckman Corporation | 1-aralykyl-5-piperazinylmethyl-2-mercaptoimidazoles and 2-alkylthioimidazoles and their use as dopamine-βhydroxylase inhibitors |
| US4882348A (en) * | 1987-12-29 | 1989-11-21 | Smithkline Beckman Corporation | 2-(aminoalkylthio)imidazoles as dopamine-β-hydroxylase inhibitors |
| FR2928544A1 (fr) * | 2008-03-17 | 2009-09-18 | Oreal | Utilisation d'inhibiteurs de la dopamine-beta hydroxylase pour la pigmentation capillaire. |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5671074A (en) * | 1979-11-12 | 1981-06-13 | Takeda Chem Ind Ltd | 1,2-disubstituted-4-halogenoimidazole-5-acetic acid derivative |
| PT78388B (en) * | 1983-04-12 | 1986-09-15 | Smithkline Beckman Corp | Dopamine-beta-hydroxylase inhibitors |
| US4532331A (en) * | 1983-04-12 | 1985-07-30 | Smithkline Beckman Corporation | 1-Benzyl-2-aminomethyl imidazole derivatives |
-
1987
- 1987-08-12 NZ NZ221427A patent/NZ221427A/en unknown
- 1987-08-14 ZW ZW153/87A patent/ZW15387A1/xx unknown
- 1987-08-14 PH PH35675A patent/PH23530A/en unknown
- 1987-08-17 AT AT87307259T patent/ATE72430T1/de not_active IP Right Cessation
- 1987-08-17 PT PT85547A patent/PT85547B/pt not_active IP Right Cessation
- 1987-08-17 WO PCT/US1987/002011 patent/WO1988001267A1/en not_active Application Discontinuation
- 1987-08-17 HU HU874557A patent/HU204037B/hu unknown
- 1987-08-17 EP EP19870905838 patent/EP0288488A4/en active Pending
- 1987-08-17 ES ES198787307259T patent/ES2038185T3/es not_active Expired - Lifetime
- 1987-08-17 ZA ZA876073A patent/ZA876073B/xx unknown
- 1987-08-17 EP EP87307259A patent/EP0260814B1/en not_active Expired - Lifetime
- 1987-08-17 AU AU79102/87A patent/AU7910287A/en not_active Abandoned
- 1987-08-17 HU HU911945A patent/HU911945D0/hu unknown
- 1987-08-17 DE DE8787307259T patent/DE3776613D1/de not_active Expired - Fee Related
- 1987-08-18 CN CN198787105734A patent/CN87105734A/zh active Pending
-
1988
- 1988-04-18 DK DK210488A patent/DK210488D0/da not_active Application Discontinuation
-
1992
- 1992-04-15 GR GR920400699T patent/GR3004345T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ZA876073B (en) | 1988-08-31 |
| DK210488A (da) | 1988-04-18 |
| ES2038185T3 (es) | 1993-07-16 |
| HUT50461A (en) | 1990-02-28 |
| PT85547A (pt) | 1988-08-17 |
| WO1988001267A1 (en) | 1988-02-25 |
| EP0260814A1 (en) | 1988-03-23 |
| HU911945D0 (en) | 1991-12-30 |
| EP0288488A1 (en) | 1988-11-02 |
| DK210488D0 (da) | 1988-04-18 |
| DE3776613D1 (de) | 1992-03-19 |
| EP0288488A4 (en) | 1990-09-12 |
| PH23530A (en) | 1989-08-25 |
| ATE72430T1 (de) | 1992-02-15 |
| CN87105734A (zh) | 1988-02-24 |
| AU7910287A (en) | 1988-03-08 |
| HU204037B (en) | 1991-11-28 |
| NZ221427A (en) | 1990-12-21 |
| EP0260814B1 (en) | 1992-02-05 |
| ZW15387A1 (en) | 1987-11-18 |
| GR3004345T3 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1993-03-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG3A | Patent granted, date of granting |
Effective date: 19940811 |
|
| MM3A | Annulment or lapse |
Free format text: LAPSE DUE TO NON-PAYMENT OF FEES Effective date: 19960229 |