GB2372742A - C2,5'-Disubstituted and N6,C2,5'-trisubstituted adenosine derivatives and their different uses - Google Patents
C2,5'-Disubstituted and N6,C2,5'-trisubstituted adenosine derivatives and their different uses Download PDFInfo
- Publication number
- GB2372742A GB2372742A GB0105337A GB0105337A GB2372742A GB 2372742 A GB2372742 A GB 2372742A GB 0105337 A GB0105337 A GB 0105337A GB 0105337 A GB0105337 A GB 0105337A GB 2372742 A GB2372742 A GB 2372742A
- Authority
- GB
- United Kingdom
- Prior art keywords
- hydrogen
- mmol
- compound
- adenosine
- alkyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
- -1 N6,C2,5'-trisubstituted adenosine Chemical class 0.000 title claims description 35
- 239000003379 purinergic P1 receptor agonist Substances 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 135
- 229910052739 hydrogen Inorganic materials 0.000 claims description 118
- 239000000203 mixture Substances 0.000 claims description 111
- 239000001257 hydrogen Substances 0.000 claims description 51
- 125000000217 alkyl group Chemical group 0.000 claims description 47
- 150000002431 hydrogen Chemical group 0.000 claims description 42
- 239000000460 chlorine Substances 0.000 claims description 25
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 125000000304 alkynyl group Chemical group 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 239000001301 oxygen Substances 0.000 claims description 15
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 239000000654 additive Substances 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- 125000001589 carboacyl group Chemical group 0.000 claims description 10
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- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
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- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 150000005215 alkyl ethers Chemical class 0.000 claims description 5
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- 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 description 92
- 229910052757 nitrogen Inorganic materials 0.000 description 86
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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
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Priority Applications (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0105337A GB2372742A (en) | 2001-03-03 | 2001-03-03 | C2,5'-Disubstituted and N6,C2,5'-trisubstituted adenosine derivatives and their different uses |
| KR1020037011508A KR100585894B1 (ko) | 2001-03-03 | 2002-03-03 | Ｃ2,5'-이치환된 및 ｎ6,ｃ2,5'-삼치환된 아데노신 유도체및 그들의 상이한 용도 |
| CNB028072014A CN1259332C (zh) | 2001-03-03 | 2002-03-03 | C2,5′－二取代的和n6，c2,5′－三取代的腺苷衍生物及其不同用途 |
| PCT/IL2002/000160 WO2002070532A2 (en) | 2001-03-03 | 2002-03-03 | C2,5'-disubstituted and n6,c2,5'-trisubstituted adenosine derivatives and their different uses |
| EP02701520A EP1368365A2 (en) | 2001-03-03 | 2002-03-03 | C2,5'-disubstituted and n6,c2,5'-trisubstituted adenosine derivatives and their different uses |
| JP2002569851A JP4359676B2 (ja) | 2001-03-03 | 2002-03-03 | Ｃ２，５’−二置換およびｎ６，ｃ２，５’−三置換アデノシン誘導体、並びにこれらの様々な使用 |
| US10/469,735 US7084127B2 (en) | 2001-03-03 | 2002-03-03 | C2,5′-disubstituted and N6, C2,5′-trisubstituted adenosine derivatives and their different uses |
| CA002439879A CA2439879C (en) | 2001-03-03 | 2002-03-03 | C2,5'-disubstituted and n6,c2,5'-trisubstituted adenosine derivatives and their different uses |
| AU2002234851A AU2002234851A1 (en) | 2001-03-03 | 2002-03-03 | C2,5'-disubstituted and n6,c2,5'-trisubstituted adenosine derivatives and their different uses |
| US10/653,464 US7189706B2 (en) | 2001-03-03 | 2003-09-03 | C2,5′-disubstituted and N6,C2,5′-trisubstituted adenosine derivatives and pharmaceutical compositions containing them |
| JP2008310049A JP2009167170A (ja) | 2001-03-03 | 2008-12-04 | Ｃ２，５’−二置換およびｎ６，ｃ２，５’−三置換アデノシン誘導体、並びにこれらの様々な使用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0105337A GB2372742A (en) | 2001-03-03 | 2001-03-03 | C2,5'-Disubstituted and N6,C2,5'-trisubstituted adenosine derivatives and their different uses |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB0105337D0 GB0105337D0 (en) | 2001-04-18 |
| GB2372742A true GB2372742A (en) | 2002-09-04 |
Family
ID=9909952
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB0105337A Withdrawn GB2372742A (en) | 2001-03-03 | 2001-03-03 | C2,5'-Disubstituted and N6,C2,5'-trisubstituted adenosine derivatives and their different uses |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US7084127B2 (https=) |
| EP (1) | EP1368365A2 (https=) |
| JP (2) | JP4359676B2 (https=) |
| KR (1) | KR100585894B1 (https=) |
| CN (1) | CN1259332C (https=) |
| AU (1) | AU2002234851A1 (https=) |
| CA (1) | CA2439879C (https=) |
| GB (1) | GB2372742A (https=) |
| WO (1) | WO2002070532A2 (https=) |
Families Citing this family (18)
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| WO2003070739A1 (en) * | 2002-02-19 | 2003-08-28 | Cv Therapeutics, Inc. | Partial and full agonists of a1 adenosine receptors |
| JP2005132767A (ja) * | 2003-10-30 | 2005-05-26 | Sumitomo Chemical Co Ltd | プリン化合物の製造方法 |
| CA2550299C (en) * | 2003-12-22 | 2010-03-30 | Christopher R. Roberts | Process for fluorocytidine derivatives |
| US20050277615A1 (en) * | 2004-05-17 | 2005-12-15 | Can-Fite Biopharma Ltd. | Pharmaceutical compositions having anti-inflammatory activity |
| AR049384A1 (es) | 2004-05-24 | 2006-07-26 | Glaxo Group Ltd | Derivados de purina |
| WO2006081665A1 (en) * | 2005-02-04 | 2006-08-10 | Uti Limited Partnership | Purine nucleoside analogs |
| GB0514809D0 (en) | 2005-07-19 | 2005-08-24 | Glaxo Group Ltd | Compounds |
| CA2720037C (en) * | 2008-03-31 | 2016-08-23 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Purine derivatives as a3 adenosine receptor-selective agonists |
| US8916570B2 (en) | 2008-03-31 | 2014-12-23 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | A3 adenosine receptor agonists and antagonists |
| WO2010014921A2 (en) * | 2008-08-01 | 2010-02-04 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | A3 adenosine receptor antagonists and partial agonists |
| US9181253B2 (en) | 2008-08-01 | 2015-11-10 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Adenosine receptor agonists, partial agonists, and antagonists |
| WO2011010306A1 (en) | 2009-07-21 | 2011-01-27 | Ramot At Tel-Aviv University Ltd. | A3 adenosine receptor ligands for modulation of pigmentation |
| LT2523669T (lt) | 2010-01-11 | 2017-04-25 | Inotek Pharmaceuticals Corporation | Akispūdžio mažinimo būdas, derinys ir rinkinys |
| PH12012501906A1 (en) | 2010-03-26 | 2013-01-14 | Inotek Pharmaceuticals Corp | Method of reducing intraocular pressure in humans using n6 -cyclopentyladenosine (cpa), cpa derivatives or prodrugs thereof |
| PT2807178T (pt) | 2012-01-26 | 2017-08-08 | Inotek Pharmaceuticals Corp | Polimorfos anidros de nitrato de (2r,3s,4r,5r)-5-(6-(ciclopentilamino)-9h-purin-9-il)-3,4-dihidroxitetrahidrofuran-2-il)}metilo e seus processos de preparação |
| US9580457B2 (en) | 2012-10-29 | 2017-02-28 | Biophore India Pharmaceuticals Pvt. Ltd. | Process for the preparation of (1-{9-[(4S, 2R, 3R, 5R)-3, 4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl)-6-aminopurin-2-yl}pyrazole-4-yl)-N-methylcarboxamide |
| NZ630759A (en) | 2013-03-15 | 2017-07-28 | Inotek Pharmaceuticals Corp | Ophthalmic formulations comprising an a1 agonist |
| JP6993323B2 (ja) * | 2016-04-22 | 2022-01-13 | 興和株式会社 | マルチプレクサ、及び該マルチプレクサを備えた撮影装置 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000072799A2 (en) * | 1999-05-27 | 2000-12-07 | The University Of Virginia Patent Foundation | Method and compositions for treating the inflammatory response |
Family Cites Families (12)
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|---|---|---|---|---|
| US4357324A (en) * | 1981-02-24 | 1982-11-02 | The United States Of America As Represented By The Department Of Health And Human Services | Prodrug derivatives of 9β-D-arabinofuranosyl-2-fluoroadenine |
| US5189027A (en) * | 1990-11-30 | 1993-02-23 | Yamasa Shoyu Kabushiki Kaisha | 2-substituted adenosine derivatives and pharmaceutical compositions for circulatory diseases |
| US5278150A (en) * | 1992-04-24 | 1994-01-11 | Whitby Research, Inc. | 2-hydrazoadenosines and their utility for the treatmeat of vascular conditions |
| US5589467A (en) * | 1993-09-17 | 1996-12-31 | Novo Nordisk A/S | 2,5',N6-trisubstituted adenosine derivatives |
| WO1997033591A1 (en) * | 1996-03-13 | 1997-09-18 | Novo Nordisk A/S | A method of treating disorders related to cytokines in mammals |
| GB9610031D0 (en) * | 1996-05-14 | 1996-07-17 | Glaxo Group Ltd | Chemical compounds |
| US5998423A (en) * | 1996-10-08 | 1999-12-07 | Therasys, Inc. | Methods for modulating melanin production |
| GB9723566D0 (en) | 1997-11-08 | 1998-01-07 | Glaxo Group Ltd | Chemical compounds |
| YU44900A (sh) | 1998-01-31 | 2003-01-31 | Glaxo Group Limited | Derivati 2-(purin-9-il)tetrahidrofuran-3,4-diola |
| AU5879299A (en) * | 1998-10-16 | 2000-05-08 | Monaghan, Sandra Marina | Adenine derivatives |
| US6605597B1 (en) * | 1999-12-03 | 2003-08-12 | Cv Therapeutics, Inc. | Partial or full A1agonists-N-6 heterocyclic 5′-thio substituted adenosine derivatives |
| US6576620B2 (en) * | 1999-12-03 | 2003-06-10 | Cv Therapeutics, Inc. | Method of identifying partial adenosine A1 receptor agonists |
-
2001
- 2001-03-03 GB GB0105337A patent/GB2372742A/en not_active Withdrawn
-
2002
- 2002-03-03 EP EP02701520A patent/EP1368365A2/en not_active Withdrawn
- 2002-03-03 WO PCT/IL2002/000160 patent/WO2002070532A2/en not_active Ceased
- 2002-03-03 CN CNB028072014A patent/CN1259332C/zh not_active Expired - Fee Related
- 2002-03-03 CA CA002439879A patent/CA2439879C/en not_active Expired - Fee Related
- 2002-03-03 US US10/469,735 patent/US7084127B2/en not_active Expired - Fee Related
- 2002-03-03 KR KR1020037011508A patent/KR100585894B1/ko not_active Expired - Fee Related
- 2002-03-03 JP JP2002569851A patent/JP4359676B2/ja not_active Expired - Fee Related
- 2002-03-03 AU AU2002234851A patent/AU2002234851A1/en not_active Abandoned
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2003
- 2003-09-03 US US10/653,464 patent/US7189706B2/en not_active Expired - Fee Related
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2008
- 2008-12-04 JP JP2008310049A patent/JP2009167170A/ja active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000072799A2 (en) * | 1999-05-27 | 2000-12-07 | The University Of Virginia Patent Foundation | Method and compositions for treating the inflammatory response |
Non-Patent Citations (6)
| Title |
|---|
| E.W. Van der Wenden et al, J.Med.Chem., (1996), 41, 102-108 * |
| E.W. van Tillburg et al, J.Med.Chem., (1999), 42, 1393-1400 * |
| H.Homma et al, J.Med.Chem., (1992), 35, 2881-2890 * |
| J.Matsuda et al, J.Med.Chem., (1992), 35, 241-252 * |
| K.Niiya et al, J.Med.Chem., (1992), 35, 4557-4561 * |
| S.Vittori et al, J.Med.Chem., (1996), 39, 4211-4217 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002070532A3 (en) | 2002-11-28 |
| CN1259332C (zh) | 2006-06-14 |
| JP4359676B2 (ja) | 2009-11-04 |
| KR100585894B1 (ko) | 2006-06-07 |
| JP2004522794A (ja) | 2004-07-29 |
| AU2002234851A1 (en) | 2002-09-19 |
| US20040127452A1 (en) | 2004-07-01 |
| US20040132686A1 (en) | 2004-07-08 |
| WO2002070532A2 (en) | 2002-09-12 |
| JP2009167170A (ja) | 2009-07-30 |
| KR20030089512A (ko) | 2003-11-21 |
| CA2439879C (en) | 2009-09-15 |
| GB0105337D0 (en) | 2001-04-18 |
| CA2439879A1 (en) | 2002-09-12 |
| EP1368365A2 (en) | 2003-12-10 |
| US7084127B2 (en) | 2006-08-01 |
| CN1537115A (zh) | 2004-10-13 |
| US7189706B2 (en) | 2007-03-13 |
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