NO323138B1 - N<O>6</O>-heterosykliske, 8-modifiserte adenosinderivater og farmasoytiske sammensetninger omfattende samme. - Google Patents
N<O>6</O>-heterosykliske, 8-modifiserte adenosinderivater og farmasoytiske sammensetninger omfattende samme. Download PDFInfo
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- NO323138B1 NO323138B1 NO20022573A NO20022573A NO323138B1 NO 323138 B1 NO323138 B1 NO 323138B1 NO 20022573 A NO20022573 A NO 20022573A NO 20022573 A NO20022573 A NO 20022573A NO 323138 B1 NO323138 B1 NO 323138B1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/167—Purine radicals with ribosyl as the saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- 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
- A61P9/10—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
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/454,485 US6294522B1 (en) | 1999-12-03 | 1999-12-03 | N6 heterocyclic 8-modified adenosine derivatives |
PCT/US2000/042396 WO2001042265A2 (en) | 1999-12-03 | 2000-11-29 | N6 heterocyclic 8-modified adenosine derivatives |
Publications (3)
Publication Number | Publication Date |
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NO20022573L NO20022573L (no) | 2002-05-30 |
NO20022573D0 NO20022573D0 (no) | 2002-05-30 |
NO323138B1 true NO323138B1 (no) | 2007-01-08 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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NO20022573A NO323138B1 (no) | 1999-12-03 | 2002-05-30 | N<O>6</O>-heterosykliske, 8-modifiserte adenosinderivater og farmasoytiske sammensetninger omfattende samme. |
Country Status (20)
Country | Link |
---|---|
US (2) | US6294522B1 (zh) |
EP (1) | EP1237898B1 (zh) |
JP (1) | JP4021196B2 (zh) |
KR (1) | KR100484987B1 (zh) |
CN (1) | CN1195772C (zh) |
AR (1) | AR029198A1 (zh) |
AT (1) | ATE292140T1 (zh) |
AU (1) | AU771242B2 (zh) |
CA (1) | CA2394861C (zh) |
DE (1) | DE60019164T2 (zh) |
ES (1) | ES2236044T3 (zh) |
HK (1) | HK1051695B (zh) |
IL (2) | IL149651A0 (zh) |
MX (1) | MXPA02005318A (zh) |
NO (1) | NO323138B1 (zh) |
NZ (1) | NZ518736A (zh) |
TR (1) | TR200201470T2 (zh) |
TW (1) | TWI268923B (zh) |
WO (1) | WO2001042265A2 (zh) |
ZA (1) | ZA200204379B (zh) |
Families Citing this family (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040171032A1 (en) * | 1996-06-06 | 2004-09-02 | Baker Brenda F. | Non-phosphorous-linked oligomeric compounds and their use in gene modulation |
US20040171028A1 (en) * | 1996-06-06 | 2004-09-02 | Baker Brenda F. | Phosphorous-linked oligomeric compounds and their use in gene modulation |
US20040161777A1 (en) * | 1996-06-06 | 2004-08-19 | Baker Brenda F. | Modified oligonucleotides for use in RNA interference |
US20040171030A1 (en) * | 1996-06-06 | 2004-09-02 | Baker Brenda F. | Oligomeric compounds having modified bases for binding to cytosine and uracil or thymine and their use in gene modulation |
US20050118605A9 (en) * | 1996-06-06 | 2005-06-02 | Baker Brenda F. | Oligomeric compounds having modified bases for binding to adenine and guanine and their use in gene modulation |
US7812149B2 (en) | 1996-06-06 | 2010-10-12 | Isis Pharmaceuticals, Inc. | 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations |
US20040161844A1 (en) * | 1996-06-06 | 2004-08-19 | Baker Brenda F. | Sugar and backbone-surrogate-containing oligomeric compounds and compositions for use in gene modulation |
US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
US9096636B2 (en) * | 1996-06-06 | 2015-08-04 | Isis Pharmaceuticals, Inc. | Chimeric oligomeric compounds and their use in gene modulation |
US20040266706A1 (en) * | 2002-11-05 | 2004-12-30 | Muthiah Manoharan | Cross-linked oligomeric compounds and their use in gene modulation |
US6403567B1 (en) * | 1999-06-22 | 2002-06-11 | Cv Therapeutics, Inc. | N-pyrazole A2A adenosine receptor agonists |
USRE47351E1 (en) | 1999-06-22 | 2019-04-16 | Gilead Sciences, Inc. | 2-(N-pyrazolo)adenosines with application as adenosine A2A receptor agonists |
US6214807B1 (en) * | 1999-06-22 | 2001-04-10 | Cv Therapeutics, Inc. | C-pyrazole 2A A receptor agonists |
AU4138601A (en) * | 1999-12-03 | 2001-06-12 | Cv Therapeutics, Inc. | Method of identifying partial adenosine a1 receptor agonists and their use in the treatment of arrhythmias |
US6605597B1 (en) * | 1999-12-03 | 2003-08-12 | Cv Therapeutics, Inc. | Partial or full A1agonists-N-6 heterocyclic 5′-thio substituted adenosine derivatives |
US20020012946A1 (en) | 2000-02-23 | 2002-01-31 | Luiz Belardinelli | Method of identifying partial agonists of the A2A receptor |
US6995148B2 (en) * | 2001-04-05 | 2006-02-07 | University Of Pittsburgh | Adenosine cyclic ketals: novel adenosine analogues for pharmacotherapy |
JP2005527502A (ja) * | 2002-02-19 | 2005-09-15 | シーブイ・セラピューティクス・インコーポレイテッド | A1アデノシン受容体の部分的および全アゴニスト |
US20050020915A1 (en) * | 2002-07-29 | 2005-01-27 | Cv Therapeutics, Inc. | Myocardial perfusion imaging methods and compositions |
CN1671399A (zh) * | 2002-07-29 | 2005-09-21 | Cv医药有限公司 | 利用a2a受体激动剂的心肌灌注显像 |
US8470801B2 (en) | 2002-07-29 | 2013-06-25 | Gilead Sciences, Inc. | Myocardial perfusion imaging methods and compositions |
EP1578765A4 (en) * | 2002-11-05 | 2008-04-23 | Isis Pharmaceuticals Inc | OLIGOMERIC COMPOUNDS CONTAINING SUGAR SUBSTITUTE AND COMPOSITIONS FOR USE IN GENE MODULATION |
US9150606B2 (en) | 2002-11-05 | 2015-10-06 | Isis Pharmaceuticals, Inc. | Compositions comprising alternating 2'-modified nucleosides for use in gene modulation |
US9150605B2 (en) | 2002-11-05 | 2015-10-06 | Isis Pharmaceuticals, Inc. | Compositions comprising alternating 2′-modified nucleosides for use in gene modulation |
AU2003291753B2 (en) * | 2002-11-05 | 2010-07-08 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
US20070161582A1 (en) * | 2003-08-08 | 2007-07-12 | Dusan Mijikovic | Pharmaceutical compositions and methods for metabolic modulation |
PT1682537E (pt) * | 2003-11-05 | 2012-06-20 | Sarcode Bioscience Inc | Moduladores de adesão celular |
US8569474B2 (en) | 2004-03-09 | 2013-10-29 | Isis Pharmaceuticals, Inc. | Double stranded constructs comprising one or more short strands hybridized to a longer strand |
US8394947B2 (en) | 2004-06-03 | 2013-03-12 | Isis Pharmaceuticals, Inc. | Positionally modified siRNA constructs |
US7884086B2 (en) | 2004-09-08 | 2011-02-08 | Isis Pharmaceuticals, Inc. | Conjugates for use in hepatocyte free uptake assays |
ATE532791T1 (de) * | 2004-09-17 | 2011-11-15 | Kissei Pharmaceutical | In der 8-stellung modifiziertes purin- nukleosidderivat und dessen medizinische verwendung |
AU2005295437B2 (en) * | 2004-10-20 | 2011-05-19 | Gilead Palo Alto, Inc. | Use of A2A adenosine receptor agonists |
LT2444079T (lt) * | 2005-05-17 | 2017-03-27 | Sarcode Bioscience Inc. | Kompozicijos ir būdai, skirti akių sutrikimų gydymui |
PT1989214T (pt) | 2006-02-03 | 2016-09-22 | Gilead Sciences Inc | Processo para preparar um agonista de recetor de adenosina a2a e polimorfos do mesmo |
CA2655310A1 (en) * | 2006-06-22 | 2008-05-29 | Cv Therapeutics, Inc. | Use of a2a adenosine receptor agonists in the treatment of ischemia |
US20090081120A1 (en) * | 2006-09-01 | 2009-03-26 | Cv Therapeutics, Inc. | Methods and Compositions for Increasing Patient Tolerability During Myocardial Imaging Methods |
JP2010502649A (ja) * | 2006-09-01 | 2010-01-28 | シーブイ・セラピューティクス・インコーポレイテッド | 心筋層画像化法中の患者の耐性を増加させるための方法および組成物 |
WO2008042796A2 (en) * | 2006-09-29 | 2008-04-10 | Cv Therapeutics, Inc. | Methods for myocardial imaging in patients having a history of pulmonary disease |
US20080267861A1 (en) * | 2007-01-03 | 2008-10-30 | Cv Therapeutics, Inc. | Myocardial Perfusion Imaging |
MX2010004281A (es) | 2007-10-19 | 2010-09-10 | Sarcode Corp | Composiciones y metodos para el tratamiento de la retinopatia diabetica. |
EP2276508A4 (en) * | 2008-04-15 | 2011-12-28 | Sarcode Bioscience Inc | RELEASE OF LFA-1 ANTAGONISTS AGAINST THE GAS-DARM SYSTEM |
EP2265124A4 (en) * | 2008-04-15 | 2011-12-28 | Sarcode Bioscience Inc | AEROSOLISED LFA-1 ANTAGONISTS FOR THE USE IN THE LOCAL TREATMENT OF IMMUNE DISEASES |
JP2011521896A (ja) * | 2008-04-15 | 2011-07-28 | サーコード コーポレイション | 免疫関連障害に対する局部治療に使用するための局所lfa−1アンタゴニスト |
WO2009139817A2 (en) | 2008-04-15 | 2009-11-19 | Sarcode Corporation | Crystalline pharmaceutical and methods of preparation and use thereof |
EP2344145A1 (en) * | 2008-09-29 | 2011-07-20 | Gilead Sciences, Inc. | Combinations of a rate control agent and an a-2-alpha receptor antagonist for use in multidetector computed tomography methods |
US8378105B2 (en) * | 2009-10-21 | 2013-02-19 | Sarcode Bioscience Inc. | Crystalline pharmaceutical and methods of preparation and use thereof |
EP3715345B1 (en) | 2012-07-25 | 2024-04-10 | Novartis AG | Preparation of lfa-1 inhibitor |
CZ308881B6 (cs) | 2014-12-09 | 2021-08-04 | Univerzita Palackého v Olomouci | 6-aryl-9-glykosylpuriny a jejich použití |
GB201820685D0 (en) * | 2018-12-19 | 2019-01-30 | NuCana plc | Synthesis of 8-chloroadenosine derivatives |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2881164A (en) * | 1955-07-18 | 1959-04-07 | American Cyanamid Co | Ribofuranosyl derivatives of 6-aralkylamino and 6-heterocyclicalkylaminopurines |
US3150124A (en) * | 1962-03-16 | 1964-09-22 | Svarnas George | Synthesis of kinetin glycosides |
JPS57171998A (en) * | 1981-04-15 | 1982-10-22 | Fujisawa Pharmaceut Co Ltd | Adenosine derivative and its salt, preparation thereof and medicinal composition containing the same |
US4616003A (en) * | 1984-10-26 | 1986-10-07 | Warner-Lambert Company | N6 -dihydroxypropyladenosines |
US4755594A (en) * | 1986-01-31 | 1988-07-05 | Warner-Lambert Company | N6 -substituted adenosines |
GB8729994D0 (en) * | 1987-12-23 | 1988-02-03 | Glaxo Group Ltd | Chemical compounds |
US5055569A (en) * | 1989-10-19 | 1991-10-08 | G. D. Searle & Co. | N-(6)-substituted adenosine compounds |
US5236902A (en) * | 1990-11-26 | 1993-08-17 | The Governors Of The University Of Alberta | Method and probes for detecting nucleoside transporter and method for producing the probes |
US5432164A (en) * | 1991-10-24 | 1995-07-11 | Novo Nordisk A/S | C2,N6 -disubstituted adenosine derivatives |
AU4226693A (en) * | 1992-05-01 | 1993-11-29 | United States Of America, Represented By The Secretary, Department Of Health And Human Services, The | Phosphorothioate derivatives of cyclic AMP analogues |
US5683989A (en) * | 1993-12-17 | 1997-11-04 | Novo Nordisk A/S | Treatment of ischemias by administration of 2,N6 -substituted adenosines |
JPH07324035A (ja) * | 1994-05-30 | 1995-12-12 | L T T Kenkyusho:Kk | 滑膜細胞増殖抑制剤及び慢性関節リウマチ治療剤 |
KR100254106B1 (ko) | 1994-06-09 | 2000-05-01 | 타이도 나오카타 | 4-퀴놀리논 유도체 또는 그의 염 |
US5789416B1 (en) * | 1996-08-27 | 1999-10-05 | Cv Therapeutics Inc | N6 mono heterocyclic substituted adenosine derivatives |
GB9723566D0 (en) * | 1997-11-08 | 1998-01-07 | Glaxo Group Ltd | Chemical compounds |
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1999
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2000
- 2000-11-29 NZ NZ518736A patent/NZ518736A/en unknown
- 2000-11-29 CN CNB008166269A patent/CN1195772C/zh not_active Expired - Fee Related
- 2000-11-29 AU AU45101/01A patent/AU771242B2/en not_active Ceased
- 2000-11-29 WO PCT/US2000/042396 patent/WO2001042265A2/en active IP Right Grant
- 2000-11-29 ES ES00992554T patent/ES2236044T3/es not_active Expired - Lifetime
- 2000-11-29 KR KR10-2002-7007096A patent/KR100484987B1/ko not_active IP Right Cessation
- 2000-11-29 TR TR2002/01470T patent/TR200201470T2/xx unknown
- 2000-11-29 EP EP00992554A patent/EP1237898B1/en not_active Expired - Lifetime
- 2000-11-29 IL IL14965100A patent/IL149651A0/xx active IP Right Grant
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- 2000-11-29 AT AT00992554T patent/ATE292140T1/de not_active IP Right Cessation
- 2000-11-29 CA CA002394861A patent/CA2394861C/en not_active Expired - Fee Related
- 2000-11-29 MX MXPA02005318A patent/MXPA02005318A/es active IP Right Grant
- 2000-11-29 DE DE60019164T patent/DE60019164T2/de not_active Expired - Lifetime
- 2000-12-01 AR ARP000106396A patent/AR029198A1/es active IP Right Grant
- 2000-12-02 TW TW089125685A patent/TWI268923B/zh not_active IP Right Cessation
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2001
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- 2002-05-31 ZA ZA200204379A patent/ZA200204379B/xx unknown
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2003
- 2003-02-28 HK HK03101536.6A patent/HK1051695B/zh not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
DE60019164T2 (de) | 2006-02-02 |
KR20030032906A (ko) | 2003-04-26 |
HK1051695A1 (en) | 2003-08-15 |
HK1051695B (zh) | 2005-06-03 |
NO20022573L (no) | 2002-05-30 |
TR200201470T2 (tr) | 2002-12-23 |
WO2001042265A3 (en) | 2002-01-03 |
CN1195772C (zh) | 2005-04-06 |
CN1402732A (zh) | 2003-03-12 |
KR100484987B1 (ko) | 2005-04-22 |
EP1237898A2 (en) | 2002-09-11 |
JP4021196B2 (ja) | 2007-12-12 |
ZA200204379B (en) | 2003-06-25 |
NZ518736A (en) | 2004-02-27 |
AU771242B2 (en) | 2004-03-18 |
NO20022573D0 (no) | 2002-05-30 |
ATE292140T1 (de) | 2005-04-15 |
US6294522B1 (en) | 2001-09-25 |
US20020045595A1 (en) | 2002-04-18 |
WO2001042265A2 (en) | 2001-06-14 |
IL149651A0 (en) | 2002-11-10 |
CA2394861C (en) | 2007-01-30 |
IL149651A (en) | 2006-08-20 |
ES2236044T3 (es) | 2005-07-16 |
AR029198A1 (es) | 2003-06-18 |
MXPA02005318A (es) | 2002-12-11 |
EP1237898B1 (en) | 2005-03-30 |
JP2003516413A (ja) | 2003-05-13 |
DE60019164D1 (de) | 2005-05-04 |
AU4510101A (en) | 2001-06-18 |
CA2394861A1 (en) | 2001-06-14 |
TWI268923B (en) | 2006-12-21 |
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