SK9702003A3 - 3,7-Diazabicyclo[3.3.0]octanes and their use in the treatment of cardiac arrhythmias - Google Patents

3,7-Diazabicyclo[3.3.0]octanes and their use in the treatment of cardiac arrhythmias Download PDF

Info

Publication number: SK9702003A3
Authority: SK; Slovakia
Prior art keywords: formula; group; compound; carbon atoms; alkyl
Prior art date: 2001-02-02

Application number

SK970-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Magnus Bjorsne

Fritiof Ponten

Gert Strandlund

Peder Svensson

Michael Wilstermann

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.)

2001-02-02

Filing date

2002-01-29

Publication date

2004-01-08

2002-01-29 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2004-01-08 Publication of SK9702003A3 publication Critical patent/SK9702003A3/sk

Links

206010003119 arrhythmia Diseases 0.000 title claims abstract description 25
238000011282 treatment Methods 0.000 title claims abstract description 19
QFCMBRXRVQRSSF-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydropyrrolo[3,4-c]pyrrole Chemical class C1NCC2CNCC21 QFCMBRXRVQRSSF-UHFFFAOYSA-N 0.000 title claims description 6
150000001875 compounds Chemical class 0.000 claims abstract description 401
230000006793 arrhythmia Effects 0.000 claims abstract description 14
230000001746 atrial effect Effects 0.000 claims abstract description 5
206010047281 Ventricular arrhythmia Diseases 0.000 claims abstract description 4
206010003130 Arrhythmia supraventricular Diseases 0.000 claims abstract description 3
238000011321 prophylaxis Methods 0.000 claims abstract 5
125000004432 carbon atom Chemical group C* 0.000 claims description 205
-1 C 1 -C 4 alkyl Chemical group 0.000 claims description 152
125000000217 alkyl group Chemical group 0.000 claims description 149
125000003118 aryl group Chemical group 0.000 claims description 130
125000001424 substituent group Chemical group 0.000 claims description 95
125000004093 cyano group Chemical group *C#N 0.000 claims description 91
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 84
229910052736 halogen Inorganic materials 0.000 claims description 81
150000002367 halogens Chemical class 0.000 claims description 80
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 78
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 73
125000002947 alkylene group Chemical group 0.000 claims description 66
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 61
238000000034 method Methods 0.000 claims description 50
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 45
125000003545 alkoxy group Chemical group 0.000 claims description 44
238000006243 chemical reaction Methods 0.000 claims description 44
239000001257 hydrogen Substances 0.000 claims description 42
229910052739 hydrogen Inorganic materials 0.000 claims description 42
238000002360 preparation method Methods 0.000 claims description 39
229910052799 carbon Inorganic materials 0.000 claims description 36
125000005843 halogen group Chemical group 0.000 claims description 36
125000000623 heterocyclic group Chemical group 0.000 claims description 33
229910052757 nitrogen Inorganic materials 0.000 claims description 33
125000004043 oxo group Chemical group O=* 0.000 claims description 27
150000001721 carbon Chemical group 0.000 claims description 25
229910052717 sulfur Inorganic materials 0.000 claims description 25
125000004430 oxygen atom Chemical group O* 0.000 claims description 24
125000005842 heteroatom Chemical group 0.000 claims description 23
125000004122 cyclic group Chemical group 0.000 claims description 21
229910052760 oxygen Inorganic materials 0.000 claims description 21
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 20
239000001301 oxygen Substances 0.000 claims description 20
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 19
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 18
239000011593 sulfur Substances 0.000 claims description 18
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 15
125000004429 atom Chemical group 0.000 claims description 15
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125000001153 fluoro group Chemical group F* 0.000 claims description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
125000002015 acyclic group Chemical group 0.000 claims description 9
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
239000003814 drug Substances 0.000 claims description 9
230000009467 reduction Effects 0.000 claims description 9
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 8
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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 7
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
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125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 3
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OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
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HKCIJFJXKPDDOG-UHFFFAOYSA-N 2-(2-benzyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)-1,3-thiazole Chemical compound C=1C=CC=CC=1CN(CC1C2)CC1CN2C1=NC=CS1 HKCIJFJXKPDDOG-UHFFFAOYSA-N 0.000 claims description 2
CBCNGWZTZVCPDT-UHFFFAOYSA-N 2-benzyl-5-cyclohexyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole Chemical compound C=1C=CC=CC=1CN(CC1C2)CC1CN2C1CCCCC1 CBCNGWZTZVCPDT-UHFFFAOYSA-N 0.000 claims description 2
JJRLPUYJOZKMFO-UHFFFAOYSA-N 2-benzyl-5-pyrimidin-2-yl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole Chemical compound C=1C=CC=CC=1CN(CC1C2)CC1CN2C1=NC=CC=N1 JJRLPUYJOZKMFO-UHFFFAOYSA-N 0.000 claims description 2
TWPUPYDZIUZHII-UHFFFAOYSA-N 5-benzyl-2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole Chemical compound C1C2CN(C)CC2CN1CC1=CC=CC=C1 TWPUPYDZIUZHII-UHFFFAOYSA-N 0.000 claims description 2
YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims description 2
JCRJVLRWMTUNTM-UHFFFAOYSA-N [N].C1NCC2CNCC21 Chemical group [N].C1NCC2CNCC21 JCRJVLRWMTUNTM-UHFFFAOYSA-N 0.000 claims description 2
239000004480 active ingredient Substances 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
230000002140 halogenating effect Effects 0.000 claims description 2
108090000623 proteins and genes Proteins 0.000 claims description 2
238000006467 substitution reaction Methods 0.000 claims description 2
YOLLCWCYOPYWGQ-UHFFFAOYSA-N CCCCCCCC.[N] Chemical compound CCCCCCCC.[N] YOLLCWCYOPYWGQ-UHFFFAOYSA-N 0.000 claims 1
239000002671 adjuvant Substances 0.000 claims 1
125000000033 alkoxyamino group Chemical group 0.000 claims 1
125000002877 alkyl aryl group Chemical group 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 99
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 78
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 53
239000000203 mixture Substances 0.000 description 48
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 34
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 34
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
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YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
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150000007942 carboxylates Chemical class 0.000 description 19
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
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238000012360 testing method Methods 0.000 description 18
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125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications

- 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
- C07D487/02—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 two hetero rings
- C07D487/04—Ortho-condensed 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

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Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Cardiology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (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)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

SK970-2003A 2001-02-02 2002-01-29 3,7-Diazabicyclo[3.3.0]octanes and their use in the treatment of cardiac arrhythmias SK9702003A3 (en)

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Application Number	Priority Date	Filing Date	Title
SE0100326A SE0100326D0 (sv)	2001-02-02	2001-02-02	New compounds
PCT/SE2002/000152 WO2002060902A1 (en)	2001-02-02	2002-01-29	3,7-diazabicyclo[3.3.0]octanes and their use in the treatment of cardiac arrhythmias

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US (1)	US7144914B2 (is)
EP (1)	EP1360187B1 (is)
JP (1)	JP2004522749A (is)
KR (1)	KR20030074764A (is)
CN (2)	CN1854138A (is)
AR (1)	AR035423A1 (is)
AT (1)	ATE298339T1 (is)
BG (1)	BG108035A (is)
BR (1)	BR0206791A (is)
CA (1)	CA2434970A1 (is)
CZ (1)	CZ20032061A3 (is)
DE (1)	DE60204755T2 (is)
EE (1)	EE200300364A (is)
ES (1)	ES2243706T3 (is)
HU (1)	HUP0302538A3 (is)
IL (1)	IL156734A0 (is)
IS (1)	IS6874A (is)
MX (1)	MXPA03006579A (is)
MY (1)	MY136788A (is)
NO (1)	NO20033434L (is)
NZ (1)	NZ526992A (is)
PL (1)	PL363454A1 (is)
PT (1)	PT1360187E (is)
RU (1)	RU2293085C2 (is)
SE (1)	SE0100326D0 (is)
SK (1)	SK9702003A3 (is)
UA (1)	UA75382C2 (is)
WO (1)	WO2002060902A1 (is)
ZA (1)	ZA200305345B (is)

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CN102718695B (zh) *	2012-06-25	2014-04-02	华东师范大学	一种氮杂双环[3.3.0]辛烷衍生物的合成方法
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JP6647592B2 (ja) *	2013-07-03	2020-02-14	ルンドベックラホーヤリサーチセンター，インク．	ピロロピロールカルバメート、および関連する有機化合物、医薬組成物、ならびにその医学的使用
EA201992707A1 (ru)	2013-11-18	2020-06-30	Глобал Блад Терапьютикс, Инк.	Соединения и их применения для модуляции гемоглобина
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KR20190015492A (ko)	2016-06-08	2019-02-13	글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드	화학적 화합물
ES2747768T3 (es)	2017-03-20	2020-03-11	Forma Therapeutics Inc	Composiciones de pirrolopirrol como activadores de quinasa de piruvato (PKR)
ES2989438T3 (es)	2018-09-19	2024-11-26	Novo Nordisk Healthcare Ag	Activación de la piruvato cinasa R
US12053458B2 (en)	2018-09-19	2024-08-06	Novo Nordisk Health Care Ag	Treating sickle cell disease with a pyruvate kinase R activating compound
US20220378756A1 (en)	2019-09-19	2022-12-01	Forma Therapeutics, Inc.	Activating pyruvate kinase r
RU2726120C1 (ru) *	2019-09-24	2020-07-09	Федеральное государственное бюджетное научное учреждение Уфимский федеральный исследовательский центр Российской академии наук	N-алкил-n-{ [3-алкил-3,8-диазабицикло[3.2.1]окта-1(7),5-диен-8-ил]метил} амины, обладающие цитотоксической активностью в отношении клеточной линии нек 293
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2001
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- 2002-01-29 IL IL15673402A patent/IL156734A0/xx unknown
- 2002-01-29 CN CNA2006100847244A patent/CN1854138A/zh active Pending
- 2002-01-29 UA UA2003076389A patent/UA75382C2/uk unknown
- 2002-01-29 WO PCT/SE2002/000152 patent/WO2002060902A1/en not_active Ceased
- 2002-01-29 MX MXPA03006579A patent/MXPA03006579A/es active IP Right Grant
- 2002-01-29 CZ CZ20032061A patent/CZ20032061A3/cs unknown
- 2002-01-29 ES ES02716531T patent/ES2243706T3/es not_active Expired - Lifetime
- 2002-01-29 AT AT02716531T patent/ATE298339T1/de not_active IP Right Cessation
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- 2002-01-29 KR KR10-2003-7010119A patent/KR20030074764A/ko not_active Ceased
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- 2002-01-29 JP JP2002561470A patent/JP2004522749A/ja active Pending
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Publication number	Publication date
IS6874A (is)	2004-07-11
DE60204755D1 (de)	2005-07-28
US20040053986A1 (en)	2004-03-18
MXPA03006579A (es)	2003-09-22
US7144914B2 (en)	2006-12-05
IL156734A0 (en)	2004-02-08
NZ526992A (en)	2005-01-28
JP2004522749A (ja)	2004-07-29
WO2002060902A1 (en)	2002-08-08
RU2293085C2 (ru)	2007-02-10
UA75382C2 (en)	2006-04-17
CZ20032061A3 (cs)	2003-10-15
CN1263758C (zh)	2006-07-12
CN1854138A (zh)	2006-11-01
BR0206791A (pt)	2004-01-27
AR035423A1 (es)	2004-05-26
ES2243706T3 (es)	2005-12-01
HK1063629A1 (en)	2005-01-07
KR20030074764A (ko)	2003-09-19
BG108035A (bg)	2003-07-28
CA2434970A1 (en)	2002-08-08
PT1360187E (pt)	2005-10-31
NO20033434D0 (no)	2003-08-01
ZA200305345B (en)	2004-10-11
HUP0302538A2 (hu)	2003-11-28
CN1489592A (zh)	2004-04-14
DE60204755T2 (de)	2006-05-18
RU2003121308A (ru)	2005-03-10
NO20033434L (no)	2003-09-23
MY136788A (en)	2008-11-28
EE200300364A (et)	2003-10-15
HUP0302538A3 (en)	2006-05-29
PL363454A1 (en)	2004-11-15
ATE298339T1 (de)	2005-07-15
SE0100326D0 (sv)	2001-02-02
EP1360187A1 (en)	2003-11-12
EP1360187B1 (en)	2005-06-22

Legal Events

Date	Code	Title	Description
2010-10-07	FB9A	Suspension of patent application procedure

Publication	Publication Date	Title
US6291475B1 (en)	2001-09-18	Bispidine antiarrhythmic compounds
SK9702003A3 (en)	2004-01-08	3,7-Diazabicyclo[3.3.0]octanes and their use in the treatment of cardiac arrhythmias
SK5062002A3 (en)	2002-11-06	New oxabispidine compounds useful in the treatment of cardiac arrhythmias
RU2262505C2 (ru)	2005-10-20	Производные азабициклооктана, фармацевтические препараты, способ профилактики или лечения, способы получения соединений, соединения
US7012074B2 (en)	2006-03-14	3,8-Diazabicyclo[3.2.1]octanes and their use in the treatment of cardiac arrhythmias
SK42003A3 (en)	2003-07-01	New bispidine compounds and their use in the treatment of cardiac arrhythmias
CZ20014495A3 (cs)	2002-05-15	Nové bispidinové sloučeniny, vhodné k léčení srdeční arytmie
SK18282001A3 (sk)	2002-12-03	Bispidínové zlúčeniny užitočné pri liečbe srdcových arytmií
US20040229900A1 (en)	2004-11-18	Bispidine compounds useful in the treatment of cardiac arrythmias
US20030212095A1 (en)	2003-11-13	New bispidine compounds and their use in the treatment of cardiac arrhythmias
AU2002226854A1 (en)	2002-08-12	3,7-diazabicyclo[3.30]octanes and their use in the treatment of cardiac arrhythmias
CZ20014493A3 (cs)	2002-05-15	Nové bispidinové sloučeniny vhodné k léčení srdeční arytmie
CZ20002222A3 (cs)	2000-11-15	Nové bispidinové sloučeniny s antiarytmickým účinkem