UA75625C2 - Condensed purine derivatives as a1 adenosine receptor antagonists - Google Patents

Condensed purine derivatives as a1 adenosine receptor antagonists Download PDF

Info

Publication number: UA75625C2
Authority: UA; Ukraine
Prior art keywords: group; alkyl; compound; substituted; amino
Prior art date: 2000-12-01

Application number

UA2003066041A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Biogen Inc

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.)

2000-12-01

Filing date

2001-11-30

Publication date

2006-05-15

2001-11-30 Application filed by Biogen Inc filed Critical Biogen Inc

2006-05-15 Publication of UA75625C2 publication Critical patent/UA75625C2/uk

Links

101150007969 ADORA1 gene Proteins 0.000 title abstract 2
239000000296 purinergic P1 receptor antagonist Substances 0.000 title description 5
229940121359 adenosine receptor antagonist Drugs 0.000 title 1
229940083251 peripheral vasodilators purine derivative Drugs 0.000 title 1
150000003212 purines Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 97
238000011282 treatment Methods 0.000 claims abstract description 11
206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 6
206010019280 Heart failures Diseases 0.000 claims abstract description 6
208000006673 asthma Diseases 0.000 claims abstract description 4
230000008085 renal dysfunction Effects 0.000 claims abstract description 4
208000001647 Renal Insufficiency Diseases 0.000 claims abstract description 3
206010012601 diabetes mellitus Diseases 0.000 claims abstract description 3
230000002497 edematous effect Effects 0.000 claims abstract description 3
201000006370 kidney failure Diseases 0.000 claims abstract description 3
208000037905 systemic hypertension Diseases 0.000 claims abstract description 3
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 48
125000000217 alkyl group Chemical group 0.000 claims description 46
-1 thiocarbamoyl Chemical group 0.000 claims description 45
238000000034 method Methods 0.000 claims description 40
125000003342 alkenyl group Chemical group 0.000 claims description 27
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
125000000304 alkynyl group Chemical group 0.000 claims description 26
238000006243 chemical reaction Methods 0.000 claims description 26
102000005962 receptors Human genes 0.000 claims description 26
108020003175 receptors Proteins 0.000 claims description 26
125000000623 heterocyclic group Chemical group 0.000 claims description 25
239000002126 C01EB10 - Adenosine Substances 0.000 claims description 24
229960005305 adenosine Drugs 0.000 claims description 24
239000002253 acid Substances 0.000 claims description 23
125000001424 substituent group Chemical group 0.000 claims description 23
239000000203 mixture Substances 0.000 claims description 22
125000003118 aryl group Chemical group 0.000 claims description 21
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239000000047 product Substances 0.000 claims description 19
201000010099 disease Diseases 0.000 claims description 17
125000004663 dialkyl amino group Chemical group 0.000 claims description 16
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125000003282 alkyl amino group Chemical group 0.000 claims description 12
SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical compound SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 claims description 11
125000004432 carbon atom Chemical group C* 0.000 claims description 10
208000035475 disorder Diseases 0.000 claims description 10
238000007363 ring formation reaction Methods 0.000 claims description 10
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125000004442 acylamino group Chemical group 0.000 claims description 9
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BBTNLADSUVOPPN-UHFFFAOYSA-N 5,6-diaminouracil Chemical compound NC=1NC(=O)NC(=O)C=1N BBTNLADSUVOPPN-UHFFFAOYSA-N 0.000 claims description 8
125000003710 aryl alkyl group Chemical group 0.000 claims description 8
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UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
125000002252 acyl group Chemical group 0.000 claims description 7
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125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 6
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125000006170 pentacyclic group Chemical group 0.000 claims description 6
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Landscapes

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UA2003066041A 2000-12-01 2001-11-30 Condensed purine derivatives as a1 adenosine receptor antagonists UA75625C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US25065800P	2000-12-01	2000-12-01
PCT/US2001/044991 WO2002044182A1 (en)	2000-12-01	2001-11-30	Condensed purine derivatives as a1 adenosine receptor antagonists

Publications (1)

Publication Number	Publication Date
UA75625C2 true UA75625C2 (en)	2006-05-15

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Application Number	Title	Priority Date	Filing Date
UA2003066041A UA75625C2 (en)	2000-12-01	2001-11-30	Condensed purine derivatives as a1 adenosine receptor antagonists

Country Status (32)

Country	Link
US (2)	US6605601B2 (de)
EP (1)	EP1347981B1 (de)
JP (2)	JP2004514723A (de)
KR (1)	KR20040011439A (de)
CN (1)	CN100497340C (de)
AR (1)	AR035400A1 (de)
AT (1)	ATE394402T1 (de)
AU (2)	AU2002219977B2 (de)
BG (1)	BG107849A (de)
BR (1)	BR0115833A (de)
CA (1)	CA2430508C (de)
CZ (1)	CZ20031513A3 (de)
DE (1)	DE60133931D1 (de)
EA (1)	EA009814B1 (de)
EE (1)	EE200300260A (de)
ES (1)	ES2305139T3 (de)
GE (1)	GEP20094697B (de)
HU (1)	HUP0400530A3 (de)
IL (1)	IL156046A0 (de)
IS (1)	IS6821A (de)
MX (1)	MXPA03004857A (de)
MY (1)	MY127120A (de)
NO (1)	NO20032483L (de)
NZ (1)	NZ526511A (de)
PL (1)	PL362642A1 (de)
SK (1)	SK6552003A3 (de)
TR (1)	TR200300766T2 (de)
TW (1)	TWI293301B (de)
UA (1)	UA75625C2 (de)
WO (1)	WO2002044182A1 (de)
YU (1)	YU42903A (de)
ZA (2)	ZA200304067B (de)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE60018216T2 (de) *	1999-12-24	2006-02-16	Kyowa Hakko Kogyo Co., Ltd.	Kondensierte purinderivate
UA75625C2 (en) *	2000-12-01	2006-05-15	Biogen Inc	Condensed purine derivatives as a1 adenosine receptor antagonists
JP2006518390A (ja) *	2003-02-19	2006-08-10	エンダシア，インコーポレイテッド	Ａ１アデノシンレセプターアンタゴニスト
US20040229901A1 (en) *	2003-02-24	2004-11-18	Lauren Otsuki	Method of treatment of disease using an adenosine A1 receptor antagonist
CA2523763A1 (en) *	2003-04-25	2004-11-11	Kyowa Hakko Kogyo Co., Ltd.	Fused pyrimidine derivative
CN1859913A (zh) *	2003-04-25	2006-11-08	美国诺华卡迪亚公司	改善肾功能损伤个体多尿症的方法
EP1636229A4 (de) *	2003-06-06	2008-07-30	Endacea Inc	A1-adenosinrezeptorantagonisten
WO2006099204A1 (en) *	2005-03-11	2006-09-21	Aderis Pharmaceuticals, Inc.	Substituted 9-alkyladenines and the use thereof
US7795427B2 (en) *	2006-02-14	2010-09-14	New York University	Methods for inhibiting osteoclast differentiation, formation, or function and for increasing bone mass
CA2648281A1 (en) *	2006-04-06	2007-10-18	Novacardia, Inc.	Co-administration of adenosine a1 receptor antagonists and anticonvulsants
NZ573735A (en)	2006-05-19	2011-10-28	Abbott Lab	Cns active fused bicycloheterocycle substituted azabicyclic alkane derivatives
JP2009540003A (ja) *	2006-06-16	2009-11-19	ノヴァカーディア，インク．	Ａａ１ｒａの低頻度投与を含む腎機能の長期間にわたる改善
US7511050B2 (en)	2006-06-23	2009-03-31	Incyte Corporation	Purinone derivatives as HM74A agonists
AR061626A1 (es)	2006-06-23	2008-09-10	Incyte Corp	Derivados de purinona como agonistas de hm74a
WO2008121882A1 (en) *	2007-03-29	2008-10-09	Novacardia, Inc.	Improved methods of administration of adenosine a1 receptor antagonists
WO2008121893A1 (en) *	2007-03-29	2008-10-09	Novacardia, Inc.	Methods of treating heart failure and renal dysfunction in individuals with an adenosine a1 receptor antagonist
WO2011063268A2 (en) *	2009-11-19	2011-05-26	Biogen Idec Ma Inc	Novel synthetic methods
WO2011123518A1 (en)	2010-03-31	2011-10-06	The United States Of America, As Represented By The Secretary, Department Of Health And Human Services	Adenosine receptor agonists for the treatment and prevention of vascular or joint capsule calcification disorders
AU2019205661B2 (en)	2018-01-04	2022-06-30	Impetis Biosciences Ltd.	Tricyclic compounds, compositions and medicinal applications thereof

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH06102662B2 (ja) *	1989-09-01	1994-12-14	協和醗酵工業株式会社	キサンチン誘導体
CA2028235C (en) *	1989-10-20	1997-01-21	Fumio Suzuki	Condensed purine derivatives
HU226369B1 (en)	1991-09-23	2008-09-29	Univ Florida State	Process for preparing substituted isoserine-esters using metal alkoxides and beta-lactams
EP0884318A4 (de) *	1996-10-07	2002-10-23	Kyowa Hakko Kogyo Kk	Kondensierte purinderivate
JP2002505687A (ja) *	1997-06-18	2002-02-19	ディスカバリーセラピューティクス，インコーポレイテッド	脈管再生手順の後の再狭窄を防止するための組成物および方法
AU4396899A (en) *	1998-07-02	2000-01-24	Kyowa Hakko Kogyo Co. Ltd.	Remedies for diabetes
DE60018216T2 (de) *	1999-12-24	2006-02-16	Kyowa Hakko Kogyo Co., Ltd.	Kondensierte purinderivate
UA75625C2 (en) *	2000-12-01	2006-05-15	Biogen Inc	Condensed purine derivatives as a1 adenosine receptor antagonists

2001
- 2001-11-30 UA UA2003066041A patent/UA75625C2/uk unknown
- 2001-11-30 WO PCT/US2001/044991 patent/WO2002044182A1/en not_active Ceased
- 2001-11-30 CA CA2430508A patent/CA2430508C/en not_active Expired - Fee Related
- 2001-11-30 CZ CZ20031513A patent/CZ20031513A3/cs unknown
- 2001-11-30 EA EA200300629A patent/EA009814B1/ru not_active IP Right Cessation
- 2001-11-30 CN CNB018208711A patent/CN100497340C/zh not_active Expired - Fee Related
- 2001-11-30 PL PL01362642A patent/PL362642A1/xx not_active Application Discontinuation
- 2001-11-30 IL IL15604601A patent/IL156046A0/xx unknown
- 2001-11-30 HU HU0400530A patent/HUP0400530A3/hu unknown
- 2001-11-30 MY MYPI20015481A patent/MY127120A/en unknown
- 2001-11-30 AT AT01998550T patent/ATE394402T1/de not_active IP Right Cessation
- 2001-11-30 KR KR10-2003-7007322A patent/KR20040011439A/ko not_active Abandoned
- 2001-11-30 MX MXPA03004857A patent/MXPA03004857A/es active IP Right Grant
- 2001-11-30 SK SK655-2003A patent/SK6552003A3/sk not_active Application Discontinuation
- 2001-11-30 TW TW090129678A patent/TWI293301B/zh active
- 2001-11-30 AU AU2002219977A patent/AU2002219977B2/en not_active Ceased
- 2001-11-30 AU AU1997702A patent/AU1997702A/xx active Pending
- 2001-11-30 DE DE60133931T patent/DE60133931D1/de not_active Expired - Lifetime
- 2001-11-30 ES ES01998550T patent/ES2305139T3/es not_active Expired - Lifetime
- 2001-11-30 EP EP01998550A patent/EP1347981B1/de not_active Expired - Lifetime
- 2001-11-30 TR TR2003/00766T patent/TR200300766T2/xx unknown
- 2001-11-30 NZ NZ526511A patent/NZ526511A/en unknown
- 2001-11-30 US US09/997,740 patent/US6605601B2/en not_active Expired - Fee Related
- 2001-11-30 BR BR0115833-3A patent/BR0115833A/pt not_active Application Discontinuation
- 2001-11-30 GE GEAP20017016A patent/GEP20094697B/en unknown
- 2001-11-30 JP JP2002546552A patent/JP2004514723A/ja active Pending
- 2001-11-30 EE EEP200300260A patent/EE200300260A/xx unknown
- 2001-11-30 AR ARP010105594A patent/AR035400A1/es unknown
- 2001-11-30 YU YU42903A patent/YU42903A/sh unknown
2003
- 2003-05-20 IS IS6821A patent/IS6821A/is unknown
- 2003-05-26 ZA ZA200304067A patent/ZA200304067B/en unknown
- 2003-05-27 US US10/446,573 patent/US7022686B2/en not_active Expired - Fee Related
- 2003-05-27 BG BG107849A patent/BG107849A/bg unknown
- 2003-06-02 NO NO20032483A patent/NO20032483L/no not_active Application Discontinuation
2004
- 2004-10-28 ZA ZA200408755A patent/ZA200408755B/xx unknown
2009
- 2009-12-07 JP JP2009278047A patent/JP2010053148A/ja not_active Withdrawn

Also Published As

Publication number	Publication date
PL362642A1 (en)	2004-11-02
NO20032483L (no)	2003-07-30
EA009814B1 (ru)	2008-04-28
MXPA03004857A (es)	2003-08-19
BG107849A (bg)	2004-01-30
TWI293301B (en)	2008-02-11
US20020111333A1 (en)	2002-08-15
IS6821A (is)	2003-05-20
EP1347981B1 (de)	2008-05-07
AU2002219977B2 (en)	2008-01-24
JP2004514723A (ja)	2004-05-20
ZA200408755B (en)	2005-07-27
NZ526511A (en)	2005-04-29
EE200300260A (et)	2003-08-15
KR20040011439A (ko)	2004-02-05
NO20032483D0 (no)	2003-06-02
CZ20031513A3 (cs)	2003-09-17
ATE394402T1 (de)	2008-05-15
CA2430508A1 (en)	2002-06-06
YU42903A (sh)	2006-05-25
EP1347981A1 (de)	2003-10-01
SK6552003A3 (en)	2003-12-02
BR0115833A (pt)	2003-10-28
AR035400A1 (es)	2004-05-26
MY127120A (en)	2006-11-30
HK1059927A1 (en)	2004-07-23
ZA200304067B (en)	2005-05-30
US7022686B2 (en)	2006-04-04
TR200300766T2 (tr)	2004-09-21
HUP0400530A2 (hu)	2004-06-28
JP2010053148A (ja)	2010-03-11
AU1997702A (en)	2002-06-11
US6605601B2 (en)	2003-08-12
IL156046A0 (en)	2003-12-23
GEP20094697B (en)	2009-06-10
CN100497340C (zh)	2009-06-10
DE60133931D1 (de)	2008-06-19
ES2305139T3 (es)	2008-11-01
CN1481387A (zh)	2004-03-10
US20030220358A1 (en)	2003-11-27
HUP0400530A3 (en)	2007-05-29
WO2002044182A1 (en)	2002-06-06
CA2430508C (en)	2010-05-18
EA200300629A1 (ru)	2003-12-25

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