UA77967C2 - Substituted of n-phenyl 2-hydroxy-2-methyl-3,3,3-trifluoropropanamide derivatives, which elevate activity of pyruvate dehydrogenase activity - Google Patents

Substituted of n-phenyl 2-hydroxy-2-methyl-3,3,3-trifluoropropanamide derivatives, which elevate activity of pyruvate dehydrogenase activity Download PDF

Info

Publication number: UA77967C2
Authority: UA; Ukraine
Prior art keywords: formula; compound; pharmaceutically acceptable; acceptable salt; ester
Prior art date: 2001-08-23

Application number

UA2004032170A

Other languages

English (en)

Ukrainian (uk)

Inventor

Roger John Butlin

Original Assignee

Astrazeneca Ab

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.)

2001-08-23

Filing date

2002-08-21

Publication date

2007-02-15

2002-08-21 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2007-02-15 Publication of UA77967C2 publication Critical patent/UA77967C2/uk

Links

230000000694 effects Effects 0.000 title claims abstract description 42
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
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UA2004032170A 2001-08-23 2002-08-21 Substituted of n-phenyl 2-hydroxy-2-methyl-3,3,3-trifluoropropanamide derivatives, which elevate activity of pyruvate dehydrogenase activity UA77967C2 (en)

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Application Number	Priority Date	Filing Date	Title
GBGB0120471.8A GB0120471D0 (en)	2001-08-23	2001-08-23	Chemical compounds
PCT/GB2002/003867 WO2003017995A1 (en)	2001-08-23	2002-08-21	Substituted n-phenyl 2-hydroxy-2-methyl-3,3,3-trifluropropanamide derivatives which elevate pyruvate dehydrogenase activity

Publications (1)

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UA77967C2 true UA77967C2 (en)	2007-02-15

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UA2004032170A UA77967C2 (en)	2001-08-23	2002-08-21	Substituted of n-phenyl 2-hydroxy-2-methyl-3,3,3-trifluoropropanamide derivatives, which elevate activity of pyruvate dehydrogenase activity

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US (2)	US20050026931A1 (is)
EP (1)	EP1425003A1 (is)
JP (1)	JP2005506976A (is)
KR (1)	KR20040030164A (is)
CN (2)	CN101328157A (is)
AR (1)	AR037497A1 (is)
AU (1)	AU2002321520B2 (is)
BR (1)	BR0212043A (is)
CA (1)	CA2458121A1 (is)
CO (1)	CO5560539A2 (is)
GB (1)	GB0120471D0 (is)
HU (1)	HUP0401149A2 (is)
IL (1)	IL160455A0 (is)
IS (1)	IS7157A (is)
MX (1)	MXPA04001552A (is)
NO (1)	NO326745B1 (is)
NZ (1)	NZ531261A (is)
PL (1)	PL368615A1 (is)
RU (1)	RU2301805C2 (is)
SA (1)	SA02230268B1 (is)
UA (1)	UA77967C2 (is)
WO (1)	WO2003017995A1 (is)
ZA (1)	ZA200401375B (is)

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KR101108196B1 (ko) *	2009-11-04	2012-01-31	(주)유로파	쓰레기 자동 집하시설의 관로 전환기
EP3022179B1 (en) *	2013-07-18	2017-11-15	Fondazione Istituto Italiano Di Tecnologia	Phenyl carbamates and their use as inhibitors of the fatty acid amide hydrolase (faah) enzyme and modulators of the d3 dopamine receptor (d3dr)

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US4537618A (en) *	1982-05-26	1985-08-27	Ciba Geigy Corporation	N-phenylsulfonyl-N'-pyrimidinylureas
GB9116069D0 (en) *	1991-07-25	1991-09-11	Ici Plc	Therapeutic amides
EP0539329A1 (de) *	1991-10-25	1993-04-28	Ciba-Geigy Ag	Acetylen-Verbindungen, verwendbar als Leukotrien-Antagonisten
GB9309716D0 (en) *	1993-05-12	1993-06-23	Zeneca Ltd	Heterocyclic derivatives
GB9310095D0 (en) *	1993-05-17	1993-06-30	Zeneca Ltd	Therapeutic compounds
GB9804648D0 (en) *	1998-03-06	1998-04-29	Zeneca Ltd	Chemical compounds
GB9805520D0 (en) *	1998-03-17	1998-05-13	Zeneca Ltd	Chemical compounds
GB9811427D0 (en) *	1998-05-29	1998-07-22	Zeneca Ltd	Chemical compounds
CZ2002773A3 (cs) *	1999-09-04	2002-06-12	Astrazeneca Ab	Substituované deriváty N-fenyl-2-hydroxy-2-methyl-3,3,3-trifluorpropanamidu, které zvyąují aktivitu pyruvátdehydrogenázy

2001
- 2001-08-23 GB GBGB0120471.8A patent/GB0120471D0/en not_active Ceased
2002
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- 2002-08-21 JP JP2003522515A patent/JP2005506976A/ja active Pending
- 2002-08-21 US US10/487,261 patent/US20050026931A1/en not_active Abandoned
- 2002-08-21 CN CNA2008101259041A patent/CN101328157A/zh active Pending
- 2002-08-21 UA UA2004032170A patent/UA77967C2/uk unknown
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- 2002-08-21 KR KR10-2004-7002620A patent/KR20040030164A/ko not_active Ceased
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- 2002-08-23 AR ARP020103172A patent/AR037497A1/es unknown
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2004
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2006
- 2006-11-20 US US11/601,854 patent/US20070208032A1/en not_active Abandoned

Also Published As

Publication number	Publication date
NO326745B1 (no)	2009-02-09
NO20040725L (no)	2004-02-19
CA2458121A1 (en)	2003-03-06
BR0212043A (pt)	2004-08-17
ZA200401375B (en)	2004-11-17
SA02230268B1 (ar)	2007-02-17
CN1571665A (zh)	2005-01-26
PL368615A1 (en)	2005-04-04
MXPA04001552A (es)	2004-05-17
RU2301805C2 (ru)	2007-06-27
NZ531261A (en)	2005-09-30
AU2002321520B2 (en)	2008-06-12
JP2005506976A (ja)	2005-03-10
WO2003017995A1 (en)	2003-03-06
IL160455A0 (en)	2004-07-25
RU2004108466A (ru)	2005-09-20
CN101328157A (zh)	2008-12-24
KR20040030164A (ko)	2004-04-08
AR037497A1 (es)	2004-11-17
IS7157A (is)	2004-02-19
US20070208032A1 (en)	2007-09-06
CO5560539A2 (es)	2005-09-30
EP1425003A1 (en)	2004-06-09
US20050026931A1 (en)	2005-02-03
HUP0401149A2 (hu)	2004-12-28
GB0120471D0 (en)	2001-10-17

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US4760067A (en)	1988-07-26	Allylsulfoxide enzyme inhibitors
ES2273725T3 (es)	2007-05-16	Derivados de hidroxiacetamidobencenosulfonamida.
RU2301805C2 (ru)	2007-06-27	Производные земещенного n-фенил 2-гидрокси-2-метил-3,3,3-трифторпропанамида, способ их получения (варианты), их применение (варианты) и фармацевтическая композиция (варианты)
US4670470A (en)	1987-06-02	Allylsulfoxide enzyme inhibitors
WO1999062873A1 (en)	1999-12-09	Benzenesulphonamide derivatives as pyruvate dehydrogenase activators
EP1757607A1 (en)	2007-02-28	N5-substituted benzo¬2,3\|azepino¬4,5-b\|indol-6-ones for treating tropical diseases
US20040224918A1 (en)	2004-11-11	Anti-mycobacterial compounds
WO1989005295A1 (en)	1989-06-15	Acyl derivatives of hydroxypyrimidines
US6689760B1 (en)	2004-02-10	Anti-mycobacterial compositions
US4558071A (en)	1985-12-10	Phenyl, trihalomethyl or heteroaryl sulfoxides having a latent allyl group bound to sulfur as enzyme inhibitors
AU2002321520A1 (en)	2003-06-05	Substituted n-phenyl 2-hydroxy-2-methyl-3,3,3-trifluropropanamide derivatives which elevate pyruvate dehydrogenase activity
TW203052B (is)	1993-04-01
Piton et al.	2018	Appendix Chapter A1: Structural studies of Mycobacterium tuberculosis DprE1 interacting with its inhibitors
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