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Novel selective inhibitors of neutral endopeptidase for the treatment of female sexual arousal disorder. Synthesis and activity of functionalized glutaramides.

Abstract：

:Female sexual arousal disorder (FSAD) is a highly prevalent sexual disorder affecting up to 40% of women. We describe herein our efforts to identify a selective neutral endopeptidase (NEP) inhibitor as a potential treatment for FSAD. The rationale for this approach, together with a description of the medicinal chemistry strategy, lead compounds, and SAR investigations are detailed. In particular, the strategy of starting with the clinically precedented selective NEP inhibitor, Candoxatrilat, and targeting low molecular weight and relatively polar mono-carboxylic acids is described. This led ultimately to the prototype development candidate R-13, for which detailed pharmacology and pharmacokinetic parameters are presented.(1)

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Pryde DC,Maw GN,Planken S,Platts MY,Sanderson V,Corless M,Stobie A,Barber CG,Russell R,Foster L,Barker L,Wayman C,Van Der Graaf P,Stacey P,Morren D,Kohl C,Beaumont K,Coggon S,Tute M

doi

10.1021/jm060133g

subject

Has Abstract

pub_date

2006-07-13 00:00:00

pages

4409-24

issue

14

eissn

0022-2623

issn

1520-4804

journal_volume

49

pub_type

杂志文章

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