HU194184B - Process for preparing mercaptoimidazole derivative as dopamine beta-hydroxylase inhibitor and pharmaceuticals comprising the same - Google Patents

Process for preparing mercaptoimidazole derivative as dopamine beta-hydroxylase inhibitor and pharmaceuticals comprising the same Download PDF

Info

Publication number: HU194184B
Authority: HU; Hungary
Prior art keywords: formula; compound; preparation; priority; compounds
Prior art date: 1984-03-19

Application number

HU85996A

Other languages

English (en)

Hungarian (hu)

Other versions

HUT37602A (en

Inventor

James S Frazee

Carl Kaiser

Lawrence I 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

1988-01-28

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

1986-01-23 Publication of HUT37602A publication Critical patent/HUT37602A/hu

1988-01-28 Publication of HU194184B publication Critical patent/HU194184B/hu

Links

OXFSTTJBVAAALW-UHFFFAOYSA-N 1,3-dihydroimidazole-2-thione Chemical class SC1=NC=CN1 OXFSTTJBVAAALW-UHFFFAOYSA-N 0.000 title claims description 5
229940122439 Hydroxylase inhibitor Drugs 0.000 title claims 3
238000004519 manufacturing process Methods 0.000 title claims 3
239000003814 drug Substances 0.000 title claims 2
102100033156 Dopamine beta-hydroxylase Human genes 0.000 title description 9
108010015720 Dopamine beta-Hydroxylase Proteins 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 71
238000002360 preparation method Methods 0.000 claims abstract description 22
238000000034 method Methods 0.000 claims abstract description 18
ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims abstract description 14
-1 alkali metal thiocyanate Chemical class 0.000 claims description 11
239000008194 pharmaceutical composition Substances 0.000 claims description 11
239000007858 starting material Substances 0.000 claims description 8
230000002378 acidificating effect Effects 0.000 claims description 7
125000001309 chloro group Chemical group Cl* 0.000 claims description 6
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 claims description 6
230000002401 inhibitory effect Effects 0.000 claims description 5
229910052783 alkali metal Inorganic materials 0.000 claims description 3
238000006243 chemical reaction Methods 0.000 claims description 3
125000001153 fluoro group Chemical group F* 0.000 claims description 3
125000003963 dichloro group Chemical group Cl* 0.000 claims description 2
PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims 2
229910052801 chlorine Inorganic materials 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 15
ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 abstract description 12
239000002253 acid Substances 0.000 abstract description 11
241000124008 Mammalia Species 0.000 abstract description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
238000001953 recrystallisation Methods 0.000 description 14
239000013078 crystal Substances 0.000 description 13
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
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239000000243 solution Substances 0.000 description 12
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DGMPVYSXXIOGJY-UHFFFAOYSA-N Fusaric acid Chemical compound CCCCC1=CC=C(C(O)=O)N=C1 DGMPVYSXXIOGJY-UHFFFAOYSA-N 0.000 description 10
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SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 8
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125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
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150000003943 catecholamines Chemical class 0.000 description 5
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OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
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FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
210000002700 urine Anatomy 0.000 description 4
HJKLEAOXCZIMPI-UHFFFAOYSA-N 2,2-diethoxyethanamine Chemical compound CCOC(CN)OCC HJKLEAOXCZIMPI-UHFFFAOYSA-N 0.000 description 3
QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 3
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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
239000004480 active ingredient Substances 0.000 description 3
230000003276 anti-hypertensive effect Effects 0.000 description 3
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000000969 carrier Substances 0.000 description 3
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 3
229940116357 potassium thiocyanate Drugs 0.000 description 3
239000000047 product Substances 0.000 description 3
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229910000033 sodium borohydride Inorganic materials 0.000 description 3
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230000035488 systolic blood pressure Effects 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
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
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
SAAKANGUQMVTHQ-UHFFFAOYSA-N 3-(3,5-difluorophenyl)propanoic acid Chemical compound OC(=O)CCC1=CC(F)=CC(F)=C1 SAAKANGUQMVTHQ-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
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DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 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
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-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
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
239000002220 antihypertensive agent Substances 0.000 description 2
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150000003935 benzaldehydes Chemical class 0.000 description 2
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DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
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125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
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239000010410 layer Substances 0.000 description 2
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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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239000000939 antiparkinson agent Substances 0.000 description 1
239000003699 antiulcer agent Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
150000001555 benzenes Chemical class 0.000 description 1
150000003939 benzylamines Chemical class 0.000 description 1
244000309466 calf Species 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
239000004927 clay Substances 0.000 description 1
230000008645 cold stress Effects 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
235000008504 concentrate Nutrition 0.000 description 1
229940109239 creatinine Drugs 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
230000002354 daily effect Effects 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000000779 depleting effect Effects 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
239000003792 electrolyte Substances 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
XTLNYNMNUCLWEZ-UHFFFAOYSA-N ethanol;propan-2-one Chemical compound CCO.CC(C)=O XTLNYNMNUCLWEZ-UHFFFAOYSA-N 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 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
201000005917 gastric ulcer Diseases 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
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
239000010931 gold Substances 0.000 description 1
229910052737 gold Inorganic materials 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical group 0.000 description 1
231100000334 hepatotoxic Toxicity 0.000 description 1
230000003082 hepatotoxic effect Effects 0.000 description 1
XLSMFKSTNGKWQX-UHFFFAOYSA-N hydroxyacetone Chemical compound CC(=O)CO XLSMFKSTNGKWQX-UHFFFAOYSA-N 0.000 description 1
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
239000007972 injectable composition Substances 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
239000001788 mono and diglycerides of fatty acids Substances 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
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 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
230000002093 peripheral effect Effects 0.000 description 1
SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical group OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
235000013849 propane Nutrition 0.000 description 1
235000019260 propionic acid Nutrition 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
150000003839 salts Chemical class 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
238000002798 spectrophotometry method Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000011699 spontaneously hypertensive rat Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000035882 stress Effects 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
229910052623 talc Inorganic materials 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
231100000563 toxic property Toxicity 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
230000002485 urinary effect Effects 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
238000005303 weighing Methods 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)
Plural Heterocyclic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

HU85996A 1984-03-19 1985-03-18 Process for preparing mercaptoimidazole derivative as dopamine beta-hydroxylase inhibitor and pharmaceuticals comprising the same HU194184B (en)

Applications Claiming Priority (1)

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

Publications (2)

Publication Number	Publication Date
HUT37602A HUT37602A (en)	1986-01-23
HU194184B true HU194184B (en)	1988-01-28

Family

ID=24363168

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HU85996A HU194184B (en)	1984-03-19	1985-03-18	Process for preparing mercaptoimidazole derivative as dopamine beta-hydroxylase inhibitor and pharmaceuticals comprising the same

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)	NZ211440A (da)
PH (1)	PH21032A (da)
ZW (1)	ZW4285A1 (da)

1985
- 1985-03-12 ZW ZW42/85A patent/ZW4285A1/xx unknown
- 1985-03-13 IL IL74586A patent/IL74586A/xx unknown
- 1985-03-13 PH PH31983A patent/PH21032A/en unknown
- 1985-03-14 NZ NZ211440A patent/NZ211440A/xx unknown
- 1985-03-14 NZ NZ222876A patent/NZ222876A/xx unknown
- 1985-03-15 DK DK118985A patent/DK118985A/da not_active Application Discontinuation
- 1985-03-18 NO NO851056A patent/NO162616C/no unknown
- 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
1991
- 1991-11-20 DK DK911896A patent/DK189691D0/da not_active Application Discontinuation

Also Published As

Publication number	Publication date
IL74586A (en)	1988-11-30
FI83309C (fi)	1991-06-25
NO851056L (no)	1985-09-20
HUT37602A (en)	1986-01-23
DK189691A (da)	1991-11-20
DK189691D0 (da)	1991-11-20
NZ222876A (en)	1988-09-29
DK118985A (da)	1985-09-20
NO162616B (no)	1989-10-16
ZW4285A1 (en)	1985-06-26
PH21032A (en)	1987-06-30
FI83309B (fi)	1991-03-15
NO162616C (no)	1990-01-24
KR850006189A (ko)	1985-10-02
FI851073A0 (fi)	1985-03-18
DK118985D0 (da)	1985-03-15
FI851073L (fi)	1985-09-20
IL74586A0 (en)	1985-06-30
NZ211440A (en)	1988-09-29

Legal Events

Date	Code	Title	Description
1990-06-28	HU90	Patent valid on 900628
1993-01-28	HMM4	Cancellation of final prot. due to non-payment of fee

Publication	Publication Date	Title
AU613984B2 (en)	1991-08-15	Dopamine-beta-hydroxylase inhibitors
IE49902B1 (en)	1986-01-08	4-substituted-3-hydroxy-3-pyrroline-2,5-dione compounds,process for their preparation and pharmaceutical compositions containing the same
EP0289380A1 (fr)	1988-11-02	Dérivés d'aryl-hétéroaryl carbinols avec activité analgésique
CA1137485A (fr)	1982-12-14	Derives de la phenyl-1 (piperidyl-4)-3 propanone-1 utilisables comme medicaments
IE52118B1 (en)	1987-06-24	Imidazole derivatives,preparation thereof and pharmaceutical preparations containing them
LU85747A1 (fr)	1986-08-04	Derives d'imidazole leur preparation et utilisation ainsi que les compositions pharmaceutiques contenant des derives
EP0168467A1 (en)	1986-01-22	Novel arylacetic acid derivatives
JPS6033818B2 (ja)	1985-08-05	新ナフタレン誘導体の製法
FR2662442A1 (fr)	1991-11-29	Trifluoromethylphenyltetrahydropyridines n-substituees procede pour leur preparation, intermediaires du procede et compositions pharmaceutiques les contenant.
FR2510113A1 (da)	1983-01-28
FR2658821A1 (fr)	1991-08-30	Nouvelles propanamines, leurs proprietes pharmacologiques et leur application a des fins therapeutiques, notamment antidiarrheuiques.
JPH03501972A (ja)	1991-05-09	ドーパミン‐β‐ヒドロキシラーゼ抑制剤
CA1167444A (fr)	1984-05-15	Derives de la chloro-3 quinoleine, procedes pour leur preparation, et leur utilisation comme medicaments
JPS62283967A (ja)	1987-12-09	ド−パミン−β−ヒドロキシラ−ゼ抑制剤
EP0179428A2 (en)	1986-04-30	Indoleacetic acid derivative and a pharmaceutical preparation
US4992459A (en)	1991-02-12	Dopamine-β-hydroxylase inhibitors
US5489592A (en)	1996-02-06	3,4-dihydro-4-oxo-3-(2-propenyl)-1-phthalazineacetic acids and derivatives, their preparations and medicines containing them
JPS62108869A (ja)	1987-05-20	ド−パミン−β−ヒドロキシラ−ゼ抑制物質
US4707488A (en)	1987-11-17	Dopamine-β-hydroxylase inhibitors and use thereof
FI83309C (fi)	1991-06-25	Foerfarande foer framstaellning av dopamin- -hydroxylas inhiberande 1-fenylalkyl-2 -merkaptoimidazolderivat.
EP0288488A1 (en)	1988-11-02	Dopamine- -hydroxylase inhibitors
EP0151052B1 (fr)	1988-03-09	Aminoéthylimidazole, composition pharmaceutique en contenant et procédé de préparation
EP0371733A2 (en)	1990-06-06	Dopamine-beta-hydroxylase inhibitors
CH625249A5 (en)	1981-09-15	Process for the preparation of imidazothiazole derivatives
CA1098446A (fr)	1981-03-31	Medicaments derives de l'indole