Description of Invention:
Researchers have been pursuing compounds that activate or inhibit adenosine A3 receptors because these cell membrane proteins have a wide range of physiological and disease-related effects and are thus considered to be promising drug targets. The adenosine A3 receptors are G-protein-coupled receptors and are found mostly in brain, lung, liver, heart, kidney, and testis. When this receptor is activated moderately, a cytoprotective effect is observed, such as reducing damage to heart cells from lack of oxygen. However, at high levels of stimulation they can cause cell death. Both agonists and antagonists are being tested for therapeutic potential, for example, treatment of cancer, heart conditions, neurological conditions, pain, asthma, inflammation and other immune implications.
Adenosine receptors have provided fertile leads for pharmaceutical development, and there are currently a variety of adenosinergic compounds advancing toward clinical trials. Therapeutics which target the adenosine A3 receptors is now an emerging focus that the major pharmaceutical companies are developing. Smaller companies are also developing drugs that stem from proprietary technology targeting adenosine A3 receptors. These companies have products in clinical trials for colorectal cancer and rheumatoid arthritis.
This invention pertains to highly potent A3 adenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides.
Inventors:
Kenneth A. Jacobson et al. (NIDDK)
Patent Status:
DHHS Reference No. E-248-2004/0 --
U.S. Provisional Application No. 60/608,823 filed 09 Sep 2004
PCT Application No. PCT/US2005/031678 filed 09 Sep 2005, which published as WO 2006/031505 on 23 Mar 2006
U.S. Patent Application No. 11/574,779 filed 06 Mar 2007
Relevant Publication: This research has been published, in part, in S. Tchilibon, B.V. Joshi, S.-K. Kim, H.T. Duong, Z.-G. Gao, and K.A. Jacobson. (N)-methanocarba 2,N6-disubstituted adenine nucleosides as highly potent and selective A3 adenosine receptor agonists. J Med Chem. 2005 Mar 24;48(6):1745-1758.
Licensing Status: In addition to licensing, the technology is available for further development through collaborative research with the inventors via a Cooperative Research and Development Agreement (CRADA).
