Novel selective inhibitors of neutral endopeptidase for the treatment of female sexual arousal disorder.

Abstract

A series of substituted glutaramides were synthesised using Candoxatrilat 1 as a lead and evaluated for potency against neutral endopeptidase (NEP) as a potential treatment for female sexual arousal disorder (FSAD). In this paper, we describe studies in which we were able to increase NEP activity substantially over the levels reported for previous compounds from this programme by appropriate substitution in both the P(1)(') and P(2)(') regions. Optimisation led to the 4-chlorophenpropylamide S-30 which was selected as a candidate for further study.

• Authors: David C Pryde, Andrew S Cook, Denise J Burring, Lyn H Jones, Stephanie Foll, Michelle Y Platts, Vivienne Sanderson, Martin Corless, Alan Stobie, Donald S Middleton, Laura Foster, Laura Barker, Piet Van Der Graaf, Peter Stacey, Christopher Kohl, Sara Coggon, Kevin Beaumont
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 15 Issue 1 Pg. 142-59 (Jan 01 2007) ISSN: 0968-0896 [Print] England
• PMID: 17070062 (Publication Type: Journal Article)

Chemical References

• Cyclohexanecarboxylic Acids
• Protease Inhibitors
• candoxatrilat
• Neprilysin

Topics

• Animals
• Cyclohexanecarboxylic Acids (chemical synthesis, chemistry, pharmacokinetics)
• Dogs
• Female
• Humans
• Hydrogen-Ion Concentration
• Male
• Molecular Structure
• Neprilysin (antagonists & inhibitors)
• Protease Inhibitors (chemical synthesis, chemistry, pharmacokinetics)
• Rabbits
• Rats
• Rats, Sprague-Dawley
• Sexual Dysfunctions, Psychological (drug therapy)
• Stereoisomerism
• Structure-Activity Relationship
• Substrate Specificity
• Swine