De Novo Design of a Picomolar Nonbasic 5-HT1BReceptor Antagonist
Journal of Medicinal Chemistry2010Vol. 53(4), pp. 1876–1880
Citations Over TimeTop 16% of 2010 papers
David A. Nugiel, Jennifer R. Krumrine, Daniel C. Hill, James Damewood, Peter R Bernstein, Cynthia D. Sobotka‐Briner, Jianwei Liu, Anna Zacco, M. Edward Pierson
Abstract
We describe herein the discovery of novel, de novo designed, 5-HT(1B) receptor antagonists that lack a basic moiety and that provide improved hERG and in vitro phospholipidosis profiles. We used a known 5-HT(1B) antagonist template as our starting point and focused on replacing the piperazine moiety. Pyrazole-based ideas were designed and synthesized among a small library of piperazine replacements. To our knowledge, these are the first potent, nonbasic, functionally active antagonists of the 5-HT(1B) receptor.
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