A new class of 5-HT2B antagonists possesses favorable potency, selectivity, and rat pharmacokinetic properties

Bioorg Med Chem Lett. 2009 Apr 15;19(8):2206-10. doi: 10.1016/j.bmcl.2009.02.126.

Neil Moss ¹, 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

Affiliations

Affiliation

1 Department of Medicinal Chemistry, Cardiovascular Disease, or Drug Discovery Support, Boehringer Ingelheim Pharmaceutical, Inc, Ridgefield, CT 06877, United States. nmoss@rdg.boehringer-ingelheim.com

PMID: 19307114 DOI: 10.1016/j.bmcl.2009.02.126

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.

Name
Email *

	Sorry, but the email address you supplied was invalid.