UA74629C2 - A derivative of 3,7-diazabicyclo [3,3,1] compounds , pharmaceutically acceptable salts thereof, a method for producing and composition based thereon as antiarrhythmic agents - Google Patents

A derivative of 3,7-diazabicyclo [3,3,1] compounds , pharmaceutically acceptable salts thereof, a method for producing and composition based thereon as antiarrhythmic agents Download PDF

Info

Publication number: UA74629C2
Authority: UA; Ukraine
Prior art keywords: oxa; compound; salt; butyl; diazadicyclo
Prior art date: 2001-04-12

Application number

UA2003098709A

Other languages

English (en)

Ukrainian (uk)

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.)

2001-04-12

Filing date

2002-12-04

Publication date

2006-01-16

2002-12-04 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2006-01-16 Publication of UA74629C2 publication Critical patent/UA74629C2/uk

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 267
150000003839 salts Chemical class 0.000 title claims abstract description 133
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238000004519 manufacturing process Methods 0.000 title claims description 7
239000003416 antiarrhythmic agent Substances 0.000 title description 2
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims abstract description 74
206010003119 arrhythmia Diseases 0.000 claims abstract description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 238
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OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 162
238000000034 method Methods 0.000 claims description 155
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238000002425 crystallisation Methods 0.000 claims description 70
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125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 46
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229910052757 nitrogen Inorganic materials 0.000 claims description 24
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125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
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238000010438 heat treatment Methods 0.000 claims description 18
230000000694 effects Effects 0.000 claims description 17
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125000005233 alkylalcohol group Chemical group 0.000 claims description 8
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125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
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229930195733 hydrocarbon Natural products 0.000 claims description 5
150000002430 hydrocarbons Chemical class 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
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150000001983 dialkylethers Chemical class 0.000 claims description 4
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TVWQKCYNJSKYOP-UHFFFAOYSA-N 2-[(3,4-dichlorobenzoyl)amino]acetic acid Chemical compound OC(=O)CNC(=O)C1=CC=C(Cl)C(Cl)=C1 TVWQKCYNJSKYOP-UHFFFAOYSA-N 0.000 claims description 3
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125000001216 2-naphthoyl group Chemical group C1=C(C=CC2=CC=CC=C12)C(=O)* 0.000 claims description 3
206010003130 Arrhythmia supraventricular Diseases 0.000 claims description 3
206010047281 Ventricular arrhythmia Diseases 0.000 claims description 3
239000004480 active ingredient Substances 0.000 claims description 3
150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
230000001746 atrial effect Effects 0.000 claims description 3
150000001242 acetic acid derivatives Chemical class 0.000 claims description 2
239000003125 aqueous solvent Chemical class 0.000 claims description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical class C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 2
PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 claims description 2
125000006308 propyl amino group Chemical group 0.000 claims description 2
KWZYUHDFABISCL-UHFFFAOYSA-N tert-butyl methanesulfonate Chemical compound CC(C)(C)OS(C)(=O)=O KWZYUHDFABISCL-UHFFFAOYSA-N 0.000 claims 2
YONLFQNRGZXBBF-UHFFFAOYSA-N 2,3-dibenzoyloxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)OC(C(O)=O)C(C(=O)O)OC(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-UHFFFAOYSA-N 0.000 claims 1
UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 claims 1
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical class CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims 1
150000001338 aliphatic hydrocarbons Chemical class 0.000 claims 1
238000001938 differential scanning calorimetry curve Methods 0.000 claims 1
239000000243 solution Substances 0.000 description 198
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239000011343 solid material Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
238000000371 solid-state nuclear magnetic resonance spectroscopy Methods 0.000 description 1
238000007614 solvation Methods 0.000 description 1
SETMGIIITGNLAS-UHFFFAOYSA-N spizofurone Chemical compound O=C1C2=CC(C(=O)C)=CC=C2OC21CC2 SETMGIIITGNLAS-UHFFFAOYSA-N 0.000 description 1
229950001870 spizofurone Drugs 0.000 description 1
238000000859 sublimation Methods 0.000 description 1
230000008022 sublimation Effects 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
208000014221 sudden cardiac arrest Diseases 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/08—Bridged systems
- 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
- A61P9/06—Antiarrhythmics

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Cardiology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Heart & Thoracic Surgery (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

UA2003098709A 2001-04-12 2002-12-04 A derivative of 3,7-diazabicyclo [3,3,1] compounds , pharmaceutically acceptable salts thereof, a method for producing and composition based thereon as antiarrhythmic agents UA74629C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
SE0101327A SE0101327D0 (sv)	2001-04-12	2001-04-12	New crystalline forms
PCT/SE2002/000725 WO2002083688A1 (en)	2001-04-12	2002-04-12	3,7-diazabicyclo [3.3.1] formulations as antiarhythmic compounds

Publications (1)

Publication Number	Publication Date
UA74629C2 true UA74629C2 (en)	2006-01-16

Family

ID=20283783

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2003098709A UA74629C2 (en)	2001-04-12	2002-12-04	A derivative of 3,7-diazabicyclo [3,3,1] compounds , pharmaceutically acceptable salts thereof, a method for producing and composition based thereon as antiarrhythmic agents

Country Status (29)

Country	Link
US (1)	US7217708B2 (cs)
EP (2)	EP1550663A1 (cs)
JP (1)	JP2004525970A (cs)
KR (1)	KR20030087078A (cs)
CN (1)	CN1269823C (cs)
AR (1)	AR035452A1 (cs)
AT (1)	ATE323095T1 (cs)
BR (1)	BR0208829A (cs)
CA (1)	CA2443470A1 (cs)
CZ (1)	CZ20032760A3 (cs)
DE (1)	DE60210598T2 (cs)
DK (1)	DK1389213T3 (cs)
EE (1)	EE200300504A (cs)
ES (1)	ES2261721T3 (cs)
HU (1)	HUP0303487A3 (cs)
IL (1)	IL158250A0 (cs)
IS (1)	IS6980A (cs)
MX (1)	MXPA03009206A (cs)
NO (1)	NO20034527L (cs)
NZ (1)	NZ528560A (cs)
PL (1)	PL367179A1 (cs)
PT (1)	PT1389213E (cs)
RU (1)	RU2286993C2 (cs)
SE (1)	SE0101327D0 (cs)
SK (1)	SK12572003A3 (cs)
TW (1)	TWI237025B (cs)
UA (1)	UA74629C2 (cs)
WO (1)	WO2002083688A1 (cs)
ZA (1)	ZA200307759B (cs)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
TWI259836B (en) *	2001-04-12	2006-08-11	Astrazeneca Ab	Modified release formulation suitable for antiarrhythmic compounds
SE0401539D0 (sv) *	2004-06-15	2004-06-15	Astrazeneca Ab	New compounds
SE0401540D0 (sv) *	2004-06-15	2004-06-15	Astrazeneca Ab	New compounds
JP2008543750A (ja) *	2005-06-13	2008-12-04	アストラゼネカアクチボラグ	心不整脈の処置用の新規オキサビスピジン化合物
WO2006137772A1 (en) *	2005-06-20	2006-12-28	Astrazeneca Ab	New physical form of n,n´- disubstituted oxabispidines
US20100222335A1 (en) *	2005-06-20	2010-09-02	Astrazeneca Ab	Process For The Preparation Of N,N'-Disubstituted Oxabispidines
TW200734342A (en) *	2005-12-15	2007-09-16	Astrazeneca Ab	New compounds for the treatment of cardiac arrhythmias
US20070219223A1 (en) *	2006-03-07	2007-09-20	Endacea, Inc.	Compositions and methods for treating respiratory disorders
PL3357911T3 (pl)	2006-06-26	2022-09-05	Akebia Therapeutics Inc.	Inhibitory prolilohydroksylazy i sposoby ich użycia
NO2686520T3 (cs)	2011-06-06	2018-03-17
WO2012170439A1 (en)	2011-06-06	2012-12-13	The Ohio State University	Methods for stabilizing hypoxia inducible factor-2 alpha as a method for treating cancer
JP2016521747A (ja)	2013-06-13	2016-07-25	アケビアセラピューティクスインコーポレイテッドＡｋｅｂｉａＴｈｅｒａｐｅｕｔｉｃｓＩｎｃ．	貧血治療のための組成物及び方法
MY180626A (en)	2013-11-15	2020-12-03	Akebia Therapeutics Inc	Solid forms of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, compositions, and uses thereof
US10150734B2 (en)	2015-01-23	2018-12-11	Akebia Therapeutics, Inc.	Solid forms of 2-(5-(3-fluorophenyl)-3-hydroxypicolinamido)acetic acid, compositions, and uses thereof
US11324734B2 (en)	2015-04-01	2022-05-10	Akebia Therapeutics, Inc.	Compositions and methods for treating anemia
US11713298B2 (en)	2018-05-09	2023-08-01	Akebia Therapeutics, Inc.	Process for preparing 2-[[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino]acetic acid
KR20210134065A (ko) *	2019-03-28	2021-11-08	주식회사 퍼스트바이오테라퓨틱스	벤조티아졸 화합물의 약제학적 염, 다형체 및 이들의 제조 방법
US11524939B2 (en)	2019-11-13	2022-12-13	Akebia Therapeutics, Inc.	Solid forms of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino} acetic acid
WO2021117767A1 (ja)	2019-12-10	2021-06-17	田辺三菱製薬株式会社	含窒素ヘテロアリールカルボキサミド酢酸誘導体の製造方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3732094A1 (de)	1987-09-24	1989-04-06	Basf Ag	Bispidinderivate als klasse iii-antiarrhythmika
US5110933A (en)	1989-11-13	1992-05-05	Board Of Regents Of Oklahoma State University	Salts of 3-azabicyclo[3.3.1]nonanes as antiarrhythmic agents, and precursors thereof
SE9704709D0 (sv) *	1997-12-17	1997-12-17	Astra Ab	Pharmaceutically active compounds
SE9902268D0 (sv)	1999-06-16	1999-06-16	Astra Ab	Pharmaceutically active compounds
SE9903759D0 (sv) *	1999-10-18	1999-10-18	Astra Ab	Pharmaceutically active compounds

2001
- 2001-04-12 SE SE0101327A patent/SE0101327D0/xx unknown
2002
- 2002-04-01 TW TW091106493A patent/TWI237025B/zh not_active IP Right Cessation
- 2002-04-02 AR ARP020101189A patent/AR035452A1/es not_active Application Discontinuation
- 2002-04-12 US US10/474,592 patent/US7217708B2/en not_active Expired - Fee Related
- 2002-04-12 AT AT02761972T patent/ATE323095T1/de not_active IP Right Cessation
- 2002-04-12 MX MXPA03009206A patent/MXPA03009206A/es active IP Right Grant
- 2002-04-12 CA CA002443470A patent/CA2443470A1/en not_active Abandoned
- 2002-04-12 DK DK02761972T patent/DK1389213T3/da active
- 2002-04-12 SK SK1257-2003A patent/SK12572003A3/sk not_active Application Discontinuation
- 2002-04-12 HU HU0303487A patent/HUP0303487A3/hu unknown
- 2002-04-12 EE EEP200300504A patent/EE200300504A/xx unknown
- 2002-04-12 PT PT02761972T patent/PT1389213E/pt unknown
- 2002-04-12 JP JP2002581443A patent/JP2004525970A/ja active Pending
- 2002-04-12 DE DE60210598T patent/DE60210598T2/de not_active Expired - Fee Related
- 2002-04-12 KR KR10-2003-7013320A patent/KR20030087078A/ko not_active Withdrawn
- 2002-04-12 CN CNB028116283A patent/CN1269823C/zh not_active Expired - Fee Related
- 2002-04-12 IL IL15825002A patent/IL158250A0/xx unknown
- 2002-04-12 EP EP05007851A patent/EP1550663A1/en not_active Withdrawn
- 2002-04-12 BR BR0208829-0A patent/BR0208829A/pt not_active IP Right Cessation
- 2002-04-12 CZ CZ20032760A patent/CZ20032760A3/cs unknown
- 2002-04-12 WO PCT/SE2002/000725 patent/WO2002083688A1/en not_active Ceased
- 2002-04-12 ES ES02761972T patent/ES2261721T3/es not_active Expired - Lifetime
- 2002-04-12 RU RU2003129231/04A patent/RU2286993C2/ru not_active IP Right Cessation
- 2002-04-12 NZ NZ528560A patent/NZ528560A/en unknown
- 2002-04-12 PL PL02367179A patent/PL367179A1/xx unknown
- 2002-04-12 EP EP02761972A patent/EP1389213B1/en not_active Expired - Lifetime
- 2002-12-04 UA UA2003098709A patent/UA74629C2/uk unknown
2003
- 2003-10-03 ZA ZA200307759A patent/ZA200307759B/en unknown
- 2003-10-08 IS IS6980A patent/IS6980A/is unknown
- 2003-10-09 NO NO20034527A patent/NO20034527L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
CA2443470A1 (en)	2002-10-24
DK1389213T3 (da)	2006-07-10
HK1061026A1 (en)	2004-09-03
HUP0303487A3 (en)	2005-04-28
RU2286993C2 (ru)	2006-11-10
DE60210598D1 (de)	2006-05-24
HUP0303487A2 (hu)	2004-01-28
NZ528560A (en)	2005-05-27
MXPA03009206A (es)	2004-01-29
PL367179A1 (en)	2005-02-21
NO20034527D0 (no)	2003-10-09
JP2004525970A (ja)	2004-08-26
RU2003129231A (ru)	2005-04-10
AR035452A1 (es)	2004-05-26
IS6980A (is)	2003-10-08
IL158250A0 (en)	2004-05-12
TWI237025B (en)	2005-08-01
KR20030087078A (ko)	2003-11-12
WO2002083688A1 (en)	2002-10-24
ES2261721T3 (es)	2006-11-16
EP1389213A1 (en)	2004-02-18
EE200300504A (et)	2003-12-15
SK12572003A3 (sk)	2004-07-07
EP1389213B1 (en)	2006-04-12
BR0208829A (pt)	2004-03-09
CN1269823C (zh)	2006-08-16
CN1514837A (zh)	2004-07-21
DE60210598T2 (de)	2007-02-08
ATE323095T1 (de)	2006-04-15
CZ20032760A3 (cs)	2004-01-14
PT1389213E (pt)	2006-07-31
EP1550663A1 (en)	2005-07-06
ZA200307759B (en)	2005-01-03
NO20034527L (no)	2003-12-10
SE0101327D0 (sv)	2001-04-12
US7217708B2 (en)	2007-05-15
US20040143000A1 (en)	2004-07-22

Publication	Publication Date	Title
UA74629C2 (en)	2006-01-16	A derivative of 3,7-diazabicyclo [3,3,1] compounds , pharmaceutically acceptable salts thereof, a method for producing and composition based thereon as antiarrhythmic agents
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