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PubMed · 16187697

BG-9928 (Biogen Idec).

Abstract

Biogen Idec, under license from CV Therapeutics, is developing BG-9928, a selective oral adenosine A, receptor antagonist, for the potential treatment of congestive heart failure. By January 2003, phase II trials of BG-9928 were ongoing.

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BibTeXRIS

Sheila A Doggrell. 2005. BG-9928 (Biogen Idec).. https://pubmed.ncbi.nlm.nih.gov/16187697/

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Adenosine A1 Receptor Antagonists↗

Potent and orally bioavailable 8-bicyclo[2.2.2]octylxanthines as adenosine A1 receptor antagonists.

In the search for a selective adenosine A1 receptor antagonist with greater aqueous solubility than the compounds currently in clinical trials as diuretics, a series of 1,4-substituted 8-cyclohexyl and 8-bicyclo[2.2.2]octylxanthines were investigated. The binding affinities of a variety of cyclohexyl and bicyclo[2.2.2]octylxanthines for the rat and human adenosine A1, A2A, A2B, and A3 receptors are presented. Bicyclo[2.2.2]octylxanthine 16 exhibited good pharmaceutical properties and in vivo activity in a rat diuresis model (ED50=0.3 mg/kg po). Optimization of the bridgehead substituent led to propionic acid 29 (BG9928), which retained high potency (hA1, Ki=7 nM) and selectivity for the adenosine A1 receptor (915-fold versus adenosine A2A receptor; 12-fold versus adenosine A2B receptor) with improved oral efficacy in the rat diuresis model (ED50=0.01 mg/kg) as well as high oral bioavailability in rat, dog, and cynomolgus monkey.

Adenosine A1 Receptor Antagonists↗

Tricyclic imidazoline derivatives as potent and selective adenosine A1 receptor antagonists.

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