Purine derivatives as A3 and A1 adenosine receptor agonists

Details Purine derivatives as A3 and A1 adenosine receptor agonists Purine derivatives as A3 and A1 adenosine receptor agonists

2005-09-02

2010-11-02

Berch, Mark L (Department: 1624)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C514S263220, C514S263230, C514S263370, C544S276000, C544S277000, C544S264000, C544S265000, C549S433000, C549S450000, C549S451000, C549S454000

Reexamination Certificate

active

07825126

ABSTRACT:
Disclosed are (N)-methanocarba adenine nucleosides of the formula:as highly potent A3adenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides, wherein R1-R6are as defined in the specification. These nucleosides are contemplated for use in the treatment a number of diseases, for example, inflammation, cardiac ischemia, stroke, asthma, diabetes, and cardiac arrhythmias. The invention also provides compounds that are agonists of both A1and A3adenosine receptors for use in cardioprotection.

REFERENCES:
patent: 5688774 (1997-11-01), Jacobson et al.
patent: 5773423 (1998-06-01), Jacobson et al.
patent: 2003/0092668 (2003-05-01), Liang et al.
patent: 2003/0216412 (2003-11-01), Jacobson et al.
patent: 2005/0261237 (2005-11-01), Boojamra et al.
patent: 2008/0312180 (2008-12-01), Liang et al.
patent: 2009/0192077 (2009-07-01), Sei et al.
patent: WO 01/51490 (2001-07-01), None
Bradford et al., A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding,Anal. Biochem., 72, 248-254 (1976).
Brun et al., Cyclin-dependent kinase (CDK) inhibitors: development of a general strategy for the construction of 2,6,9-trisubstituted purine libraries. Part 1,Tet. Lett., 42, 8161-8164 (2001).
Cohen et al., Enantiospecific Syntheses of Leukotrienes C4, D4, and E4and [14,15-3H2] Leukotriene E4Dimethyl Ester,J. Amer. Chem. Soc., 105, 3661-3672 (1983).
Elzein et al., 2-Pyrazolyl-N6-Substituted Adenosine Derivatives as High Affinity and Selective Adenosine A3Receptor Agonists,J. Med. Chem., 47, 4766-4773 (2004).
Fishman et al., An agonist to the A3adenosine receptor inhibits colon carcinoma growth in mice via modulation of GSK-3β and NF-κB,Oncogene, 23, 2465-2471 (2004).
Fredholm et al., International Union of Pharmacology. XXV. Nomenclature and Classification of Adenosine Receptors,Pharmacol. Rev., 53, 527-552 (2001).
Gallo-Rodriguez et al., Structure-Activity Relationships of N6-Benzyladenosine-5′—uronamides as A3-Selective Adenosine Agonists,J. Med. Chem., 37, 636-646 (1994).
Gao et al., N6-Substituted adenosine derivatives: selectivity, efficacy, and species differences at A3adenosine receptors,Biochem. Pharmacol., 65(10), 1675-1684 (2003).
Gao et al., Structural Determinants of A3Adenosine Receptor Activation: Nucleoside Ligands at the Agonist/Antagonist Boundary,J. Med. Chem., 45, 4471-4484 (2002).
Jacobson et al., Engineering of A3Adenosine and P2Y Nucleotide Receptors and their Ligands,Drug. Devel. Res., 58, 330-339 (2003).
Joshi et al., New Synthetic Route to (N)Methanocarba Nucleosides Acting as Potent A3 Adenosine Receptors Agonists, 227thACS National Meeting, Boston, MA, Abstract MEDI 256 (2004).
Kim et al, 2-Substitution of N6-Benzyladenosine-5′-uronamides Enhances Selectivity for A3Adenosine Receptors,J. Med. Chem., 37, 3614-3621 (1994).
Kim et al., 2-Substitution of Adenine Nucleotide Analogues Containing a Bicyclo[3.1.0]hexane Ring System Locked in a Northern Conformation: Enhanced Potency as P2Y1Receptor Antagonists,J. Med. Chem., 46, 4974-4987 (2003).
Lee et al., Ring-Constrained (N)-Methanocarba Nucleosides as Adenosine Receptor Agonists: Independent 5′-Uronamide and 2′-Deoxy Modifications,Bioorg. Med. Chem. Lett., 11, 1333-1337 (2001).
Liu et al., Evidence that the adenosine A3receptor may mediate the protection afforded by preconditioning in the isolated rabbit heart,Cardiovasc Res., 28, 1057-1061 (1994).
Nordstedt et al., A Modification of a Protein-Binding Method for Rapid Quantification of cAMP in Cell-Culture Supernatants and Body Fluid,Anal. Biochem., 189, 231-234 (1990).
Ohno et al., Modulation of adenosine receptor affinity and intrinsic efficacy in adenine nucleosides substituted at the 2-position,Bioorg. Med. Chem., 12, 2995-3007 (2004).
Ohta et al., Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage,Nature, 414, 916-920 (2001).
Olah et al.,125I-4-Aminobenzy1-5′-N-methylcarboxamidoadenosine, a High Affinity Radioligand for the Rat A3Adenosine Receptor,Mol. Pharmacol., 45, 978-982 (1994).
Post et al., Biochemical Methods for Detection and Measurement of Cyclic AMP and Adenylyl Cyclase Activity,Methods Mol. Biol., 126, 363-374 (2000).
Ramkumar et al., The A3Adenosine Receptor Is the Unique Adenosine Receptor Which Facilitates Release of Allergic Mediators in Mast Cells,J. Biol. Chem., 268, 16887-16890 (1993).
Rao et al., Stereoselective Transformations Leading to Pentono -1, 4-Lactones,J. Carbohydr. Chem., 15, 975-984 (1996).
Ravi et al., Synthesis and Purine Receptor Affinity of 6-Oxopurine Nucleosides and Nucleotides Containing (N)-Methanocarba-pseudoribose Rings,Bioorganic&Medicinal Chemistry Letters, 11, 2295-2300 (2001).
Richer et al., Equilibration d'imines cyclaniques,Can. J. Chem., 48(4), 570 (1970).
Strickler et al., Direct Preconditioning of Cultured Chick Ventricular Myocytes,J. Clin. Invest., 98, 1773-1779 (1996).
Tchilibon et al., Exploring distal regions of the A3adenosine receptor binding site: sterically constrained N6-(2-phenylethyl)adenosine derivatives as potent ligands,Bioorg. Med. Chem., 12, 2021-2034 (2004).
Tchilibon et al., (N)-methanocarba 2,N6-Disubstituted Adenine Nucleosides as Highly Potent and Selective A3Adenosine Receptor Agonists,J. Medicinal Chemistry, 48, 1745-1758 (2005).
Tucker et al., Design and synthesis of a series of potent and orally bioavailable noncovalent thrombin inhibitors that utilize nonbasic groups in the P1 position,J. Med. Chem., 41. 3210-3219 (1998).
Von Lubitz et al., Adenosine A3receptor stimulation and cerebral ischemia,Eur. J. Pharmacol., 263, 59-67 (1994).
Zwart et al., A functional screening of adenosine analogues at the adenosine A2Breceptor: a search for potent agonists,Nucleosides and Nucleotides, 17, 969-986 (1998).

Affiliated with

Also associated with

Rating

Purine derivatives as A3 and A1 adenosine receptor agonists does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Purine derivatives as A3 and A1 adenosine receptor agonists, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Purine derivatives as A3 and A1 adenosine receptor agonists will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-4201843