Available Technology

Methanocarba Cycloalkyl Nucleoside Analogues

Purines such as adenosine and ATP have been shown to play a wide array of roles in biological systems such as inter alia, modulator of vasodilation and hypotension, muscle relaxant, central depressant, inhibitor of platelet aggregation, regulator of energy supply/demand, responder to oxygen availability, neurotransmitter and neuromodulator. All P1 and P2 receptor nucleoside ligands suffer from chemical instability that is caused by the labile glycosidic linkage in the sugar moiety of the nucleoside. However, it has been found that relatively few ribose modifications are tolerated by the presently known agonists and antagonists of P1 and P2 receptors.
Patent Abstract: 
Purines such as adenosine and ATP have been shown to play a wide array of roles in biological systems such as inter alia, modulator of vasodilation and hypotension, muscle relaxant, central depressant, inhibitor of platelet aggregation, regulator of energy supply/demand, responder to oxygen availability, neurotransmitter and neuromodulator. All P1 and P2 receptor nucleoside ligands suffer from chemical instability that is caused by the labile glycosidic linkage in the sugar moiety of the nucleoside. However, it has been found that relatively few ribose modifications are tolerated by the presently known agonists and antagonists of P1 and P2 receptors. The NIH announces a new technology wherein a new class of nucleoside and nucleotide analogs has been identified that serve as selective agonists or antagonists for P1 and P2 receptors. The technology relates to a chemical modification of purines and pyrimidines, which provide enhanced therapeutic profile and potentially greater in vivo stability, because of the absence of a glycosidic bond. The P2Y receptor agonists and antagonists could potentially be used in immune modulation, inflammation, cardiovascular diseases, neurodegeneration, diabetes, and cancer. In addition, the A3 receptor agonists and antagonists could be useful in cardioprotection, neuroprotection, and asthma. Kenneth Jacobson(NIDDK)➽ more inventions... U.S. Pat:7,087,589issued 2006-08-08 US Application No. 11/500,860 US Application No. PCT/US01/00981 K.A. Jacobson et al., "Methanocarba analogues of purine nucleosides as potent and selective adenosine receptor agonists," J. Med. Chem., 2000, 43:2196-2203. H.S. Kim et al., "Methanocarba modification of uracil and adenine nucleotides: High potency of Northern ring conformation at P2Y1, P2Y2, or P2Y4 and P2Y11, but not P2Y6 receptors," J. Med. Chem., 2002, 45:208-218. Betty Tong, Ph.D. Email:tongb@mail.nih.gov Phone: E-176-1999/0 Updated:May 1, 2003
Inventors: 
Kenneth Jacobson
Internal Laboratory Ref #: 
E-176-1999/0
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