FI83309C - Foerfarande foer framstaellning av dopamin- -hydroxylas inhiberande 1-fenylalkyl-2 -merkaptoimidazolderivat. - Google Patents

Foerfarande foer framstaellning av dopamin- -hydroxylas inhiberande 1-fenylalkyl-2 -merkaptoimidazolderivat. Download PDF

Info

Publication number: FI83309C
Authority: FI; Finland
Prior art keywords: mol; compounds; acid; mercaptoimidazole; solution
Prior art date: 1984-03-19

Application number

FI851073A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI851073A0 (fi

FI851073L (fi

FI83309B (fi

Inventor

Carl Kaiser

James Simpson Frazee

Lawrence Ivan Kruse

Original Assignee

Smithkline Beckman Corp

Priority date (The priority date 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 date listed.)

1984-03-19

Filing date

1985-03-18

Publication date

1991-06-25

1985-03-18 Application filed by Smithkline Beckman Corp filed Critical Smithkline Beckman Corp

1985-03-18 Publication of FI851073A0 publication Critical patent/FI851073A0/fi

1985-09-20 Publication of FI851073L publication Critical patent/FI851073L/fi

1991-03-15 Application granted granted Critical

1991-03-15 Publication of FI83309B publication Critical patent/FI83309B/fi

1991-06-25 Publication of FI83309C publication Critical patent/FI83309C/fi

Links

150000001875 compounds Chemical class 0.000 claims description 59
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 28
238000000034 method Methods 0.000 claims description 16
229960003638 dopamine Drugs 0.000 claims description 14
102100033156 Dopamine beta-hydroxylase Human genes 0.000 claims description 12
238000002360 preparation method Methods 0.000 claims description 10
239000002253 acid Substances 0.000 claims description 5
125000000217 alkyl group Chemical group 0.000 claims description 4
125000003963 dichloro group Chemical group Cl* 0.000 claims description 4
PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 claims description 4
ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 claims description 3
ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims description 3
238000006243 chemical reaction Methods 0.000 claims description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
229910052801 chlorine Chemical group 0.000 claims 2
239000000460 chlorine Chemical group 0.000 claims 2
229910052731 fluorine Inorganic materials 0.000 claims 2
239000011737 fluorine Chemical group 0.000 claims 2
108010015720 Dopamine beta-Hydroxylase Proteins 0.000 claims 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 1
230000001404 mediated effect Effects 0.000 claims 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
239000000243 solution Substances 0.000 description 21
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
230000000694 effects Effects 0.000 description 14
239000013078 crystal Substances 0.000 description 13
239000000543 intermediate Substances 0.000 description 13
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 12
LYIIBVSRGJSHAV-UHFFFAOYSA-N 2-aminoacetaldehyde Chemical compound NCC=O LYIIBVSRGJSHAV-UHFFFAOYSA-N 0.000 description 10
239000000203 mixture Substances 0.000 description 10
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 9
229960002748 norepinephrine Drugs 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
DGMPVYSXXIOGJY-UHFFFAOYSA-N Fusaric acid Chemical compound CCCCC1=CC=C(C(O)=O)N=C1 DGMPVYSXXIOGJY-UHFFFAOYSA-N 0.000 description 8
241001465754 Metazoa Species 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
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KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
230000002829 reductive effect Effects 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
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
-1 aminoacetaldehyde acetal Chemical class 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
150000003943 catecholamines Chemical class 0.000 description 4
125000001309 chloro group Chemical group Cl* 0.000 description 4
239000002934 diuretic Substances 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
OXFSTTJBVAAALW-UHFFFAOYSA-N 1,3-dihydroimidazole-2-thione Chemical group SC1=NC=CN1 OXFSTTJBVAAALW-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
206010020772 Hypertension Diseases 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000002220 antihypertensive agent Substances 0.000 description 3
150000003935 benzaldehydes Chemical class 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
230000001882 diuretic effect Effects 0.000 description 3
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239000003814 drug Substances 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
239000007788 liquid Substances 0.000 description 3
230000001452 natriuretic effect Effects 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
229940116357 potassium thiocyanate Drugs 0.000 description 3
239000000725 suspension Substances 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
210000002700 urine Anatomy 0.000 description 3
QHGUCRYDKWKLMG-QMMMGPOBSA-N (R)-octopamine Chemical compound NC[C@H](O)C1=CC=C(O)C=C1 QHGUCRYDKWKLMG-QMMMGPOBSA-N 0.000 description 2
HJKSYRZNDJQTJQ-OWOJBTEDSA-N (e)-3-(3,5-dichlorophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC(Cl)=CC(Cl)=C1 HJKSYRZNDJQTJQ-OWOJBTEDSA-N 0.000 description 2
MBAWRXICVNIUGY-OWOJBTEDSA-N (e)-3-(3,5-difluorophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC(F)=CC(F)=C1 MBAWRXICVNIUGY-OWOJBTEDSA-N 0.000 description 2
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-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
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
RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
QHGUCRYDKWKLMG-MRVPVSSYSA-N Octopamine Natural products NC[C@@H](O)C1=CC=C(O)C=C1 QHGUCRYDKWKLMG-MRVPVSSYSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
230000003276 anti-hypertensive effect Effects 0.000 description 2
229940127088 antihypertensive drug Drugs 0.000 description 2
235000010323 ascorbic acid Nutrition 0.000 description 2
229960005070 ascorbic acid Drugs 0.000 description 2
239000011668 ascorbic acid Substances 0.000 description 2
230000036772 blood pressure Effects 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
239000000969 carrier Substances 0.000 description 2
DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
239000012043 crude product Substances 0.000 description 2
230000002354 daily effect Effects 0.000 description 2
230000007423 decrease Effects 0.000 description 2
229940030606 diuretics Drugs 0.000 description 2
125000001153 fluoro group Chemical group F* 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
239000010410 layer Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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230000008018 melting Effects 0.000 description 2
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239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
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CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
239000000047 product Substances 0.000 description 2
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 2
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238000001953 recrystallisation Methods 0.000 description 2
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238000011699 spontaneously hypertensive rat Methods 0.000 description 2
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FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 1
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MKOFKSXCLASLCV-UHFFFAOYSA-N 3-[(2,4-dichlorophenyl)methyl]-1h-imidazole-2-thione Chemical compound ClC1=CC(Cl)=CC=C1CN1C(=S)NC=C1 MKOFKSXCLASLCV-UHFFFAOYSA-N 0.000 description 1
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VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
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NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
DZGWFCGJZKJUFP-UHFFFAOYSA-N Tyramine Natural products NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 1
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
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239000008272 agar Substances 0.000 description 1
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150000001413 amino acids Chemical class 0.000 description 1
WGQKYBSKWIADBV-UHFFFAOYSA-N aminomethyl benzene Natural products NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 1
239000003708 ampul Substances 0.000 description 1
230000000202 analgesic effect Effects 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
229940035678 anti-parkinson drug Drugs 0.000 description 1
230000001754 anti-pyretic effect Effects 0.000 description 1
230000000767 anti-ulcer Effects 0.000 description 1
229940030600 antihypertensive agent Drugs 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
150000003939 benzylamines Chemical class 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
239000002775 capsule Substances 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
229940109239 creatinine Drugs 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000010586 diagram Methods 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000003480 eluent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
230000003203 everyday effect Effects 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229940074045 glyceryl distearate Drugs 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
231100000334 hepatotoxic Toxicity 0.000 description 1
229960002474 hydralazine Drugs 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000012750 in vivo screening Methods 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
229940102223 injectable solution Drugs 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
230000002452 interceptive effect Effects 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
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 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical group OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 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
238000006722 reduction reaction Methods 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 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
DZGWFCGJZKJUFP-UHFFFAOYSA-O tyraminium Chemical compound [NH3+]CCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-O 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

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/38—One sulfur atom
- C07D239/40—One sulfur atom as doubly bound sulfur atom or as unsubstituted mercapto radical

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Plural Heterocyclic Compounds (AREA)

FI851073A 1984-03-19 1985-03-18 Foerfarande foer framstaellning av dopamin- -hydroxylas inhiberande 1-fenylalkyl-2 -merkaptoimidazolderivat. FI83309C (fi)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US59066584A	1984-03-19	1984-03-19
US59066584		1984-03-19

Publications (4)

Publication Number	Publication Date
FI851073A0 FI851073A0 (fi)	1985-03-18
FI851073L FI851073L (fi)	1985-09-20
FI83309B FI83309B (fi)	1991-03-15
FI83309C true FI83309C (fi)	1991-06-25

Family

ID=24363168

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI851073A FI83309C (fi)	1984-03-19	1985-03-18	Foerfarande foer framstaellning av dopamin- -hydroxylas inhiberande 1-fenylalkyl-2 -merkaptoimidazolderivat.

Country Status (9)

Country	Link
KR (1)	KR850006189A (da)
DK (2)	DK118985A (da)
FI (1)	FI83309C (da)
HU (1)	HU194184B (da)
IL (1)	IL74586A (da)
NO (1)	NO162616C (da)
NZ (2)	NZ222876A (da)
PH (1)	PH21032A (da)
ZW (1)	ZW4285A1 (da)

1985
- 1985-03-12 ZW ZW42/85A patent/ZW4285A1/xx unknown
- 1985-03-13 PH PH31983A patent/PH21032A/en unknown
- 1985-03-13 IL IL74586A patent/IL74586A/xx unknown
- 1985-03-14 NZ NZ222876A patent/NZ222876A/xx unknown
- 1985-03-14 NZ NZ211440A patent/NZ211440A/xx unknown
- 1985-03-15 DK DK118985A patent/DK118985A/da not_active Application Discontinuation
- 1985-03-18 FI FI851073A patent/FI83309C/fi not_active IP Right Cessation
- 1985-03-18 HU HU85996A patent/HU194184B/hu not_active IP Right Cessation
- 1985-03-18 KR KR1019850001737A patent/KR850006189A/ko not_active Ceased
- 1985-03-18 NO NO851056A patent/NO162616C/no unknown
1991
- 1991-11-20 DK DK189691A patent/DK189691A/da not_active Application Discontinuation

Also Published As

Publication number	Publication date
DK118985D0 (da)	1985-03-15
HU194184B (en)	1988-01-28
NZ211440A (en)	1988-09-29
NO162616B (no)	1989-10-16
NO162616C (no)	1990-01-24
FI851073A0 (fi)	1985-03-18
KR850006189A (ko)	1985-10-02
DK118985A (da)	1985-09-20
IL74586A0 (en)	1985-06-30
FI851073L (fi)	1985-09-20
IL74586A (en)	1988-11-30
NO851056L (no)	1985-09-20
ZW4285A1 (en)	1985-06-26
NZ222876A (en)	1988-09-29
FI83309B (fi)	1991-03-15
PH21032A (en)	1987-06-30
DK189691D0 (da)	1991-11-20
HUT37602A (en)	1986-01-23
DK189691A (da)	1991-11-20

Legal Events

Date	Code	Title	Description
2004-08-31	MM	Patent lapsed	Owner name: SMITHKLINE BECKMAN CORPORATION

Publication	Publication Date	Title
AU613984B2 (en)	1991-08-15	Dopamine-beta-hydroxylase inhibitors
FI81098C (fi)	1990-09-10	Foerfarande foer framstaellning av nya terapeutiskt verksamma tiazolidindionderivat.
US4808599A (en)	1989-02-28	Benzo[b]thiophene- and benzo[b]furancarboxamide derivatives, pharmaceutical compositions and use
JPS6089474A (ja)	1985-05-20	モルフイナン誘導体，その製造方法，及び該化合物を含有する抗腫瘍剤
NZ197246A (en)	1984-09-28	Imidazole derivatives and antifungal pharmaceutical compositions
JP5128959B2 (ja)	2013-01-23	新規ヒスチジン誘導体
FR2549061A1 (fr)	1985-01-18	Derives du spirosuccinimide utilisables comme medicaments
FI84057C (fi)	1991-10-10	Foerfarande foer framstaellning av terapeutiskt aktiva fluorallylaminderivat.
KR100372312B1 (ko)	2003-05-09	신규의히드록시믹산유도체,그를포함한약제학적조성물및그의제조방법
FI83309C (fi)	1991-06-25	Foerfarande foer framstaellning av dopamin- -hydroxylas inhiberande 1-fenylalkyl-2 -merkaptoimidazolderivat.
JPS6040422B2 (ja)	1985-09-11	置換１‐アルキルチオフエニル―２，３，４，５―テトラヒドロ―１ｈ―３―ベンズアゼピン化合物
US4616017A (en)	1986-10-07	Aminohydroxypropoxy substituted aryl compounds
FR2658821A1 (fr)	1991-08-30	Nouvelles propanamines, leurs proprietes pharmacologiques et leur application a des fins therapeutiques, notamment antidiarrheuiques.
KR0139201B1 (ko)	1998-05-15	아미노벤젠술폰산 유도체
US4206210A (en)	1980-06-03	Alkylthio-7,8-dihdroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines having dopaminergic activity
US4992459A (en)	1991-02-12	Dopamine-β-hydroxylase inhibitors
FI95244B (fi)	1995-09-29	Analogiamenetelmä valmistaa lääkeaineina käyttökelpoisia uusia karboksimidiamidijohdannaisia tai niiden farmaseuttisesti sopivia happoadditiosuoloja
JP5121018B2 (ja)	2013-01-16	新規ヒスチジン誘導体
US4707488A (en)	1987-11-17	Dopamine-β-hydroxylase inhibitors and use thereof
EP0151052B1 (fr)	1988-03-09	Aminoéthylimidazole, composition pharmaceutique en contenant et procédé de préparation
EP0221720B1 (en)	1990-06-27	Dihydropyridines
EP0260814A1 (en)	1988-03-23	Dopamine-Beta-hydroxylase inhibitors
EP0103500B1 (fr)	1988-01-13	Dérivés de phénéthyl-1alpha-phényl-pipéridine-3-propanenitrile, leur préparation et leur application en thérapeutique
JP2853404B2 (ja)	1999-02-03	抗不整脈薬
JP2535533B2 (ja)	1996-09-18	ベンゾジオキソ−ル誘導体