KR101350741B1 - 이미다졸 유도체 및 그의 도파민-베타-하이드록실라제의 말초 신경 선택적 억제제로서의 용도 - Google Patents

이미다졸 유도체 및 그의 도파민-베타-하이드록실라제의 말초 신경 선택적 억제제로서의 용도 Download PDF

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Publication number: KR101350741B1
Authority: KR; South Korea
Prior art keywords: compound; mmol; ethyl acetate; dihydroimidazole; mixture
Prior art date: 2002-10-11

Application number

KR1020127005102A

Other languages

English (en)

Korean (ko)

Other versions

KR20120038014A (ko

Inventor

데이비드 알렉산더 레아르몬스

다 실바 파트리키오 마누엘 비에라 아라우조 소아레스

알렉산더 벨리아에브

Original Assignee

바이알 - 포르텔라 앤드 씨에이 에스에이

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.)

2002-10-11

Filing date

2003-10-10

Publication date

2014-01-10

2003-10-10 Application filed by 바이알 - 포르텔라 앤드 씨에이 에스에이 filed Critical 바이알 - 포르텔라 앤드 씨에이 에스에이

2003-10-10 Priority claimed from PCT/GB2003/004430 external-priority patent/WO2004033447A1/en

2012-04-20 Publication of KR20120038014A publication Critical patent/KR20120038014A/ko

2014-01-10 Application granted granted Critical

2014-01-10 Publication of KR101350741B1 publication Critical patent/KR101350741B1/ko

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108010015720 Dopamine beta-Hydroxylase Proteins 0.000 title description 4
102100033156 Dopamine beta-hydroxylase Human genes 0.000 title description 4
229940124639 Selective inhibitor Drugs 0.000 title description 2
150000002460 imidazoles Chemical class 0.000 title 1
229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 68
229910052717 sulfur Inorganic materials 0.000 claims abstract description 6
229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
XPEYBHVMUUQGFT-OGFXRTJISA-N (3r)-6,8-difluoro-3,4-dihydro-2h-chromen-3-amine;hydrochloride Chemical compound Cl.C1=C(F)C=C2C[C@@H](N)COC2=C1F XPEYBHVMUUQGFT-OGFXRTJISA-N 0.000 claims description 4
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 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
239000011737 fluorine Substances 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
125000004430 oxygen atom Chemical group O* 0.000 claims description 3
125000004434 sulfur atom Chemical group 0.000 claims description 3
XESORRKVRNORPM-SSDOTTSWSA-N (3r)-6,8-difluoro-3,4-dihydro-2h-chromen-3-amine Chemical compound C1=C(F)C=C2C[C@@H](N)COC2=C1F XESORRKVRNORPM-SSDOTTSWSA-N 0.000 claims 1
125000001153 fluoro group Chemical group F* 0.000 claims 1
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
238000000034 method Methods 0.000 abstract description 20
238000002360 preparation method Methods 0.000 abstract description 5
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XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 94
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239000000203 mixture Substances 0.000 description 35
239000000243 solution Substances 0.000 description 28
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 25
SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 25
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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
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CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
YZZVIKDAOTXDEB-JTQLQIEISA-N nepicastat Chemical compound NCC1=CNC(=S)N1[C@@H]1CC2=CC(F)=CC(F)=C2CC1 YZZVIKDAOTXDEB-JTQLQIEISA-N 0.000 description 17
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 11
238000004440 column chromatography Methods 0.000 description 11
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239000003480 eluent Substances 0.000 description 11
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239000003921 oil Substances 0.000 description 10
ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 10
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YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
238000001914 filtration Methods 0.000 description 9
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239000002244 precipitate Substances 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
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210000004556 brain Anatomy 0.000 description 7
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KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
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230000002889 sympathetic effect Effects 0.000 description 6
206010019280 Heart failures Diseases 0.000 description 5
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238000001727 in vivo Methods 0.000 description 5
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102000004190 Enzymes Human genes 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
125000003118 aryl group Chemical group 0.000 description 4
210000003169 central nervous system Anatomy 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
229910000033 sodium borohydride Inorganic materials 0.000 description 4
239000012279 sodium borohydride Substances 0.000 description 4
NSLATPDKWVAAIL-UHFFFAOYSA-N 3,4-dihydro-2h-chromen-3-amine;hydron;chloride Chemical compound Cl.C1=CC=C2CC(N)COC2=C1 NSLATPDKWVAAIL-UHFFFAOYSA-N 0.000 description 3
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KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
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HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
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FSXUXANZPDLESG-QRPNPIFTSA-N (2s)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=C(F)C=C2C[C@@H](N)CCC2=C1F FSXUXANZPDLESG-QRPNPIFTSA-N 0.000 description 2
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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 2
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125000004663 dialkyl amino group Chemical group 0.000 description 2
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DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
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238000012360 testing method Methods 0.000 description 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/409—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having four such rings, e.g. porphine derivatives, bilirubin, biliverdine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

KR1020127005102A 2002-10-11 2003-10-10 이미다졸 유도체 및 그의 도파민-베타-하이드록실라제의 말초 신경 선택적 억제제로서의 용도 KR101350741B1 (ko)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
GB0223719A GB2393958A (en)	2002-10-11	2002-10-11	Peripherally-selective imidazole inhibitors of dopamine-beta-hydroxylase
GB0223719.6		2002-10-11
GB0224306.1		2002-10-18
GB0224306A GB2394223B (en)	2002-10-11	2002-10-18	Peripherally-selective inhibitors of dopamine-beta-hydroxylase and method of their preparation
PCT/GB2003/004430 WO2004033447A1 (en)	2002-10-11	2003-10-10	Imidazole derivatives and their use as peripherally-selective inhibitors of dopamine-beta-hydroxylase

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KR101350741B1 true KR101350741B1 (ko)	2014-01-10

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KR (1)	KR101350741B1 (de)
CN (1)	CN100393715C (de)
AR (2)	AR041589A1 (de)
AT (5)	ATE505465T1 (de)
CY (2)	CY1108452T1 (de)
DE (4)	DE60336276D1 (de)
DK (2)	DK1908760T3 (de)
ES (5)	ES2309279T3 (de)
GB (2)	GB2393958A (de)
HK (1)	HK1116188A1 (de)
SI (2)	SI1908760T1 (de)

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GB0708818D0 (en) *	2007-05-08	2007-06-13	Portela & Ca Sa	Compounds
BR112013015864B1 (pt) *	2010-12-22	2021-11-09	Bial - Portela & C.A., S.A.	Processo para purificar um composto de forma cristalina a de (r)-5-(2-benzilamino)etil)-1- (6,8-difluorocroman-3-il)-1h-imidazol-2(3h)-tiona
GB201316410D0 (en) *	2013-09-13	2013-10-30	Bial Portela & Ca Sa	Processes for preparing peripherally-selective inhibitors of dopamine-?-hydroxylase and intermediates for use therein

Citations (1)

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Publication number	Priority date	Publication date	Assignee	Title
EP0335375A2 (de)	1988-03-30	1989-10-04	Warner-Lambert Company	Antihyperlipidemische und antiatherosclerotische Verbindungen und Zusammensetzungen

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JP2581556B2 (ja) *	1986-05-06	1997-02-12	メレルダウファーマスーティカルズインコーポレーテッド	新規なドパミンベ−タヒドロキシラ−ゼ抑制剤
WO1995029165A2 (en) *	1994-04-26	1995-11-02	Syntex (U.S.A.) Inc.	Benzocycloalkylaz0lethione derivatives as dopamin beta-hydroxylase inhibitors

2002
- 2002-10-11 GB GB0223719A patent/GB2393958A/en not_active Withdrawn
- 2002-10-18 GB GB0224306A patent/GB2394223B/en not_active Expired - Lifetime
2003
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- 2003-10-10 DE DE60336275T patent/DE60336275D1/de not_active Expired - Lifetime
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- 2003-10-10 AT AT03256420T patent/ATE403652T1/de active
- 2003-10-10 ES ES07076125T patent/ES2364919T3/es not_active Expired - Lifetime
- 2003-10-10 ES ES07076122T patent/ES2361938T3/es not_active Expired - Lifetime
2008
- 2008-10-09 HK HK08111214.9A patent/HK1116188A1/xx not_active IP Right Cessation
- 2008-10-24 CY CY20081101204T patent/CY1108452T1/el unknown
2011
- 2011-07-01 CY CY20111100639T patent/CY1112457T1/el unknown
2014
- 2014-03-18 AR ARP140101283A patent/AR095674A2/es unknown

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Also Published As

Publication number	Publication date
ATE500247T1 (de)	2011-03-15
GB0224306D0 (en)	2002-11-27
ATE500248T1 (de)	2011-03-15
ES2364919T3 (es)	2011-09-16
SI1408038T1 (sl)	2008-10-31
ES2361939T3 (es)	2011-06-24
DK1908760T3 (da)	2011-07-25
DE60336276D1 (de)	2011-04-14
ATE505465T1 (de)	2011-04-15
GB2393958A (en)	2004-04-14
DK1408038T3 (da)	2008-11-24
KR20120038014A (ko)	2012-04-20
GB2394223B (en)	2007-05-16
AR041589A1 (es)	2005-05-26
CN1726211A (zh)	2006-01-25
ES2361938T3 (es)	2011-06-24
AR095674A2 (es)	2015-11-04
GB0223719D0 (en)	2002-11-20
HK1116188A1 (en)	2008-12-19
DE60322642D1 (de)	2008-09-18
ES2384118T3 (es)	2012-06-29
CY1108452T1 (el)	2014-04-09
CN100393715C (zh)	2008-06-11
GB2394223A (en)	2004-04-21
DE60336772D1 (de)	2011-05-26
ES2309279T3 (es)	2008-12-16
DE60336275D1 (de)	2011-04-14
ATE550335T1 (de)	2012-04-15
CY1112457T1 (el)	2015-12-09
ATE403652T1 (de)	2008-08-15
SI1908760T1 (sl)	2011-05-31

Publication	Publication Date	Title
KR101155159B1 (ko)	2012-06-11	이미다졸 유도체 및 그의 도파민-베타-하이드록실라제의말초 신경 선택적 억제제로서의 용도
KR101598482B1 (ko)	2016-02-29	도파민-베타-히드록실라아제의 저해제인 1,3-디히드로이미다졸-2-티온 유도체
HU198479B (en)	1989-10-30	Process for producing 1-substituted imidazole derivatives and pharmaceutical compositions comprising same as active ingredient
KR101350741B1 (ko)	2014-01-10	이미다졸 유도체 및 그의 도파민-베타-하이드록실라제의 말초 신경 선택적 억제제로서의 용도
CZ4296A3 (en)	1996-06-12	Novel (1-phenyl-1-heterocyclyl)methanol and (1-phenyl-1-heterocyclyl)methylamine derivatives
EP0463944A1 (de)	1992-01-02	Acylbenzoxazolinone, Verfahren zu ihrer Herstellung und pharmazeutische Zusammensetzungen die sie enthalten
HU205087B (en)	1992-03-30	Process for producing 2,2'-bi(1h-imidazole) derivatives
CA2674305A1 (en)	2008-07-17	Therapy
WO2002053157A1 (en)	2002-07-11	Thiazolidine derivative
WO2016205031A1 (en)	2016-12-22	Fluoropyridyl pyrazol compounds

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