Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1372520 | Bioorganic & Medicinal Chemistry Letters | 2011 | 4 Pages |
Abstract
The V1a receptor has emerged as an attractive target for a range of indications including Raynaud’s disease and dysmenorrhoea. As part of an effort to discover a new class of orally active V1a antagonist, we optimised a highly lipophilic, metabolically unstable lead into a range of potent, selective and metabolically stable V1a antagonists. In this communication, we demonstrate the series-dependent effect of limiting the number of rotatable bonds in order to decrease Cytochrome P450-mediated metabolism. This effort culminated in the discovery of PF-184563, a novel, selective V1a antagonist with excellent in vitro and in vivo properties.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Patrick S. Johnson, Thomas Ryckmans, Justin Bryans, Dave M. Beal, Kevin N. Dack, Neil Feeder, Anthony Harrison, Mark Lewis, Helen J. Mason, James Mills, Julie Newman, Christelle Pasquinet, Dave J. Rawson, Lee R. Roberts, Rachel Russell, Deborah Spark,