title: 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.affiliation: Department of Discovery Chemistry, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. David.Pryde@Pfizer.com
authors.forename: David C
authors.initials: DC
authors.lastname: Pryde
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Cook
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Burring
authors.forename: Lyn H
authors.initials: LH
authors.lastname: Jones
authors.forename: Stephanie
authors.initials: S
authors.lastname: Foll
authors.forename: Michelle Y
authors.initials: MY
authors.lastname: Platts
authors.forename: Vivienne
authors.initials: V
authors.lastname: Sanderson
authors.forename: Martin
authors.initials: M
authors.lastname: Corless
authors.forename: Alan
authors.initials: A
authors.lastname: Stobie
authors.forename: Donald S
authors.initials: DS
authors.lastname: Middleton
authors.forename: Laura
authors.initials: L
authors.lastname: Foster
authors.forename: Laura
authors.initials: L
authors.lastname: Barker
authors.forename: Piet
authors.initials: P
authors.lastname: Van Der Graaf
authors.forename: Peter
authors.initials: P
authors.lastname: Stacey
authors.forename: Christopher
authors.initials: C
authors.lastname: Kohl
authors.forename: Sara
authors.initials: S
authors.lastname: Coggon
authors.forename: Kevin
authors.initials: K
authors.lastname: Beaumont
mesh_terms: D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics; D004285:Dogs; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D015394:Molecular Structure; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D020018:Sexual Dysfunctions, Psychological / Q000188:drug therapy*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013552:Swine
chemical_list: D003509:Cyclohexanecarboxylic Acids; D011480:Protease Inhibitors; C060942:candoxatrilat; D015260:Neprilysin