Neil Moss,
Younggi Choi,
Derek Cogan,
Adam Flegg,
Andreas Kahrs,
Pui Loke,
Orietta Meyn,
Raj Nagaraja,
Spencer Napier,
Ashley Parker, J Thomas Peterson,
Philip Ramsden,
Christopher Sarko,
Donna Skow,
Josh Tomlinson,
Heather Tye,
Mark Whitaker
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ABSTRACT: We have been exploring the potential of 5-HT(2B) antagonists as a therapy for chronic heart failure. To assess the potential of this therapeutic approach, we sought compounds possessing the following attributes: (a) potent and selective antagonism of the 5-HT(2B) receptor, (b) low impact of serum proteins on potency, and (c) desirable pharmacokinetic properties. This Letter describes our investigation of a biphenyl benzimidazole class of compounds that resulted in 5-HT(2B) antagonists possessing the above attributes. Improving potency in a human serum albumin shift assay proved to be the most significant SAR discovery.
Bioorganic & medicinal chemistry letters 05/2009; 19(8):2206-10. · 2.65 Impact Factor
