SK285582B6 - Opticky aktívny derivát pyridyl-4H-1,2,4-oxadiazínu a jeho použitie na výrobu liečiva na liečenie vaskulárnych ochorení - Google Patents

Opticky aktívny derivát pyridyl-4H-1,2,4-oxadiazínu a jeho použitie na výrobu liečiva na liečenie vaskulárnych ochorení Download PDF

Info

Publication number: SK285582B6
Authority: SK; Slovakia
Prior art keywords: pyridyl; oxadiazine; piperidinyl; dihydro; methyl
Prior art date: 1998-12-14

Application number

SK234-2001A

Other languages

English (en)

Slovak (sk)

Other versions

SK2342001A3 (en

Inventor

Andrea Jedn�Kovits

L�Szl� �R�Gdi

L�Szl� D�Nes

Istv�N Kurucz

Ede M�Rv�Nyos

Mih�Ly Barab�S

Ern� B�Csy

Zsuzsanna Korom

Zolt�N Nagy

L�Szl� �Rge

Jen Szilbereky

K�Roly Acsai

P�Ter Krajcsi

Zita Cs�Kai

Magdolna T�R�K

Original Assignee

Biorex Kutat� �S Fejleszt� Rt.

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.)

1998-12-14

Filing date

1999-12-07

Publication date

2007-04-05

1999-12-07 Application filed by Biorex Kutat� �S Fejleszt� Rt. filed Critical Biorex Kutat� �S Fejleszt� Rt.

2001-08-06 Publication of SK2342001A3 publication Critical patent/SK2342001A3/sk

2007-04-05 Publication of SK285582B6 publication Critical patent/SK285582B6/sk

Links

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Classifications

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- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5355—Non-condensed oxazines and containing further heterocyclic rings
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

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Animal Behavior & Ethology (AREA)
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Pharmacology & Pharmacy (AREA)
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Heart & Thoracic Surgery (AREA)
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SK234-2001A 1998-12-14 1999-12-07 Opticky aktívny derivát pyridyl-4H-1,2,4-oxadiazínu a jeho použitie na výrobu liečiva na liečenie vaskulárnych ochorení SK285582B6 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
HU9802897A HU226617B1 (en)	1998-12-14	1998-12-14	Optically active pyridyl-4h-1,2,4-oxadiazine derivatives, and pharmaceutical composition containing the compound as active ingredient
PCT/HU1999/000095 WO2000035914A1 (en)	1998-12-14	1999-12-07	Optically active pyridyl-4h-1,2,4-oxadiazine derivative and its use in the treatment of vascular diseases

Publications (2)

Publication Number	Publication Date
SK2342001A3 SK2342001A3 (en)	2001-08-06
SK285582B6 true SK285582B6 (sk)	2007-04-05

Family

ID=10991166

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK234-2001A SK285582B6 (sk)	1998-12-14	1999-12-07	Opticky aktívny derivát pyridyl-4H-1,2,4-oxadiazínu a jeho použitie na výrobu liečiva na liečenie vaskulárnych ochorení

Country Status (27)

Country	Link
US (1)	US6384029B1 (sr)
EP (1)	EP1147105B1 (sr)
JP (2)	JP2002532498A (sr)
KR (1)	KR100661774B1 (sr)
AT (1)	ATE266027T1 (sr)
AU (1)	AU765336B2 (sr)
BG (1)	BG65179B1 (sr)
BR (1)	BR9913982A (sr)
CA (1)	CA2340734C (sr)
CZ (1)	CZ300764B6 (sr)
DE (1)	DE69917074T2 (sr)
DK (1)	DK1147105T3 (sr)
EE (1)	EE04551B1 (sr)
ES (1)	ES2219091T3 (sr)
HR (1)	HRP20010133B1 (sr)
HU (1)	HU226617B1 (sr)
IL (1)	IL141515A (sr)
NO (1)	NO317649B1 (sr)
PL (1)	PL196584B1 (sr)
PT (1)	PT1147105E (sr)
RS (1)	RS50129B (sr)
RU (1)	RU2222538C2 (sr)
SI (1)	SI1147105T1 (sr)
SK (1)	SK285582B6 (sr)
UA (1)	UA70340C2 (sr)
WO (1)	WO2000035914A1 (sr)
ZA (1)	ZA200101182B (sr)

Families Citing this family (12)

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Publication number	Priority date	Publication date	Assignee	Title
CA2471752A1 (en)	2002-01-11	2003-07-17	Biorex Kutato Es Fejlesztoe Rt.	Carboxamidine derivatives and their use in the treatment of vascular diseases
KR100678577B1 (ko) *	2006-09-11	2007-02-06	조만규	가정용 분전함
EP2484371B1 (en)	2008-06-26	2014-12-17	Orphazyme APS	Use of Hsp70 as a regulator of enzymatic activity
KR20110084514A (ko)	2008-11-18	2011-07-25	산텐 세이야꾸 가부시키가이샤	피리딘-3-카르발데히드 ｏ-(피페리딘-1-일-프로필)-옥심 유도체를 유효 성분으로서 함유하는 망맥락막 변성 질환의 치료제
RU2013125923A (ru)	2010-11-30	2015-01-10	Орфазиме Апс	СПОСОБЫ УВЕЛИЧЕНИЯ ВНУТРИКЛЕТОЧНОЙ АКТИВНОСТИ Hsp70
HUP1100534A2 (en)	2011-09-26	2013-04-29	Balazs Dr Hazay	Pharmaceutical composition for the treatment of muscle atrophy
US10709700B2 (en)	2014-09-15	2020-07-14	Orphazyme A/S	Arimoclomol formulation
EP3442530A1 (en)	2016-04-13	2019-02-20	Orphazyme A/S	Heat shock proteins and cholesterol homeostasis
SI3448382T1 (sl)	2016-04-29	2021-03-31	Orphazyme A/S, c/o COBIS A/S	Arimoclomol za zdravljenje motenj, povezanih z glukocerebrozidazo
JP2020520947A (ja)	2017-05-24	2020-07-16	オーファザイムエー／エス	熱ショックタンパク質誘導因子および前頭側頭障害
US20210164997A1 (en)	2018-05-28	2021-06-03	Orphazyme A/S	Hsp70 protein levels in pbmc samples as biomarker for disease
WO2022106614A1 (en)	2020-11-19	2022-05-27	Orphazyme A/S	Processes for preparing arimoclomol citrate and intermediates thereof

Family Cites Families (4)

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Publication number	Priority date	Publication date	Assignee	Title
AT395853B (de) *	1991-01-31	1993-03-25	Chem Pharm Forsch Gmbh	Neue imidazolderivate, verfahren zu ihrer herstellung und ihre verwendung
HU222994B1 (hu) *	1995-11-02	2004-01-28	BIOREX Kutató és Fejlesztő Rt.	Hidroxilaminszármazékok és azok alkalmazása sejtek molekuláris chaperon-termelésének fokozására alkalmas gyógyszerkészítmények előállítására
WO1997016349A1 (en) *	1995-11-03	1997-05-09	Global Trading Uk Limited	Apparatus for dispensing and filling bags at a checkout counter of a supermarket
UA64716C2 (en) *	1996-08-09	2004-03-15		Pharmaceuticals for therapy or prevention of illnesses connected with dysfunction of vascular endothelial cells

1998
- 1998-12-14 HU HU9802897A patent/HU226617B1/hu not_active IP Right Cessation
1999
- 1999-07-12 UA UA2001063850A patent/UA70340C2/uk unknown
- 1999-12-07 US US09/762,949 patent/US6384029B1/en not_active Expired - Lifetime
- 1999-12-07 DK DK99961225T patent/DK1147105T3/da active
- 1999-12-07 JP JP2000588174A patent/JP2002532498A/ja not_active Withdrawn
- 1999-12-07 RS YUP-250/01A patent/RS50129B/sr unknown
- 1999-12-07 CA CA002340734A patent/CA2340734C/en not_active Expired - Lifetime
- 1999-12-07 RU RU2001118854/04A patent/RU2222538C2/ru not_active IP Right Cessation
- 1999-12-07 PL PL346767A patent/PL196584B1/pl not_active IP Right Cessation
- 1999-12-07 EE EEP200100188A patent/EE04551B1/xx not_active IP Right Cessation
- 1999-12-07 CZ CZ20011550A patent/CZ300764B6/cs not_active IP Right Cessation
- 1999-12-07 EP EP99961225A patent/EP1147105B1/en not_active Expired - Lifetime
- 1999-12-07 IL IL14151599A patent/IL141515A/xx not_active IP Right Cessation
- 1999-12-07 KR KR1020017002870A patent/KR100661774B1/ko not_active Expired - Fee Related
- 1999-12-07 DE DE69917074T patent/DE69917074T2/de not_active Expired - Lifetime
- 1999-12-07 HR HR20010133A patent/HRP20010133B1/xx not_active IP Right Cessation
- 1999-12-07 AU AU17906/00A patent/AU765336B2/en not_active Expired
- 1999-12-07 PT PT99961225T patent/PT1147105E/pt unknown
- 1999-12-07 SI SI9930566T patent/SI1147105T1/xx unknown
- 1999-12-07 WO PCT/HU1999/000095 patent/WO2000035914A1/en not_active Ceased
- 1999-12-07 SK SK234-2001A patent/SK285582B6/sk not_active IP Right Cessation
- 1999-12-07 BR BR9913982-0A patent/BR9913982A/pt not_active Application Discontinuation
- 1999-12-07 ES ES99961225T patent/ES2219091T3/es not_active Expired - Lifetime
- 1999-12-07 AT AT99961225T patent/ATE266027T1/de active
2001
- 2001-02-12 ZA ZA200101182A patent/ZA200101182B/en unknown
- 2001-03-14 BG BG105342A patent/BG65179B1/bg unknown
- 2001-05-10 NO NO20012310A patent/NO317649B1/no not_active IP Right Cessation
2011
- 2011-06-08 JP JP2011128516A patent/JP5620340B2/ja not_active Expired - Lifetime

Also Published As

Publication number	Publication date
BG65179B1 (bg)	2007-05-31
US6384029B1 (en)	2002-05-07
CA2340734C (en)	2008-10-21
AU765336B2 (en)	2003-09-18
SK2342001A3 (en)	2001-08-06
RS50129B (sr)	2009-03-25
JP2002532498A (ja)	2002-10-02
CZ300764B6 (cs)	2009-08-05
HU226617B1 (en)	2009-04-28
HRP20010133A2 (en)	2002-02-28
HUP9802897A2 (hu)	2000-11-28
DE69917074T2 (de)	2005-05-12
KR100661774B1 (ko)	2006-12-28
AU1790600A (en)	2000-07-03
EP1147105A1 (en)	2001-10-24
JP2011201916A (ja)	2011-10-13
EE04551B1 (et)	2005-10-17
NO20012310D0 (no)	2001-05-10
EE200100188A (et)	2002-08-15
IL141515A (en)	2005-09-25
EP1147105B1 (en)	2004-05-06
YU25001A (sh)	2004-07-15
JP5620340B2 (ja)	2014-11-05
KR20010073129A (ko)	2001-07-31
NO20012310L (no)	2001-05-10
RU2222538C2 (ru)	2004-01-27
SI1147105T1 (en)	2004-08-31
ES2219091T3 (es)	2004-11-16
CA2340734A1 (en)	2000-06-22
ATE266027T1 (de)	2004-05-15
HU9802897D0 (en)	1999-02-01
HUP9802897A3 (en)	2001-08-28
BR9913982A (pt)	2001-06-12
NO317649B1 (no)	2004-11-29
PL196584B1 (pl)	2008-01-31
IL141515A0 (en)	2002-03-10
HRP20010133B1 (en)	2005-02-28
DK1147105T3 (da)	2004-06-01
ZA200101182B (en)	2002-02-12
UA70340C2 (en)	2004-10-15
CZ20011550A3 (cs)	2001-08-15
DE69917074D1 (de)	2004-06-09
PT1147105E (pt)	2004-07-30
PL346767A1 (en)	2002-02-25
BG105342A (en)	2001-12-29
WO2000035914A1 (en)	2000-06-22

Legal Events

Date	Code	Title	Description
2012-09-03	MM4A	Patent lapsed due to non-payment of maintenance fees	Effective date: 20111207

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CS228943B2 (cs)	1984-04-16	Způsob výroby substituovaných derivátů 1,4-dihydropyridinu
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EP0017079A1 (en)	1980-10-15	Benzenesulfinamides, a process for the preparation thereof and medicaments containing them