Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

New pyrimido[4,5-d]azepines 7 are disclosed as potent 5-HT(2C) receptor agonists. A preferred example, 7b had minimal activation at either the 5-HT(2A) or 5-HT(2B) receptors combined with robust efficacy in a preclinical canine model of stress urinary incontinence (SUI) and attractive pharmacokinetic and safety properties. Based on this profile, 7b (PF-3246799) was identified as a candidate for clinical development for the treatment of SUI. In addition, it proved to be critical to build an understanding of the translation between recombinant cell-based systems, native tissue preparations and in vivo preclinical models. This was a significant undertaking and proved to be crucial in compound selection.

Original publication

DOI

10.1016/j.bmcl.2010.11.120

Type

Journal article

Journal

Bioorg Med Chem Lett

Publication Date

01/05/2011

Volume

21

Pages

2715 - 2720

Keywords

Animals, Azepines, Disease Models, Animal, Dogs, Male, Molecular Structure, Pyrimidines, Rats, Serotonin 5-HT2 Receptor Agonists, Urinary Incontinence