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.
MeSH terms
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Animals
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Cyclohexanecarboxylic Acids / chemical synthesis*
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Cyclohexanecarboxylic Acids / chemistry*
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Cyclohexanecarboxylic Acids / pharmacokinetics
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Dogs
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Female
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Humans
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Hydrogen-Ion Concentration
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Male
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Molecular Structure
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Neprilysin / antagonists & inhibitors*
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / chemistry*
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Protease Inhibitors / pharmacokinetics
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Rabbits
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Rats
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Rats, Sprague-Dawley
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Sexual Dysfunctions, Psychological / drug therapy*
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Stereoisomerism
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Structure-Activity Relationship
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Substrate Specificity
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Swine
Substances
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Cyclohexanecarboxylic Acids
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Protease Inhibitors
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candoxatrilat
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Neprilysin