Tandem optimization of target activity and elimination of mutagenic potential in a potent series of N-aryl bicyclic hydantoin-based selective androgen receptor modulators.
Bioorg Med Chem Lett
; 17(7): 1860-4, 2007 Apr 01.
Article
in En
| MEDLINE
| ID: mdl-17292608
ABSTRACT
Pharmacokinetic studies in cynomolgus monkeys with a novel prototype selective androgen receptor modulator revealed trace amounts of an aniline fragment released through hydrolytic metabolism. This aniline fragment was determined to be mutagenic in an Ames assay. Subsequent concurrent optimization for target activity and avoidance of mutagenicity led to the identification of a pharmacologically superior clinical candidate without mutagenic potential.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Androgen
/
Chemistry, Pharmaceutical
/
Hydantoins
/
Androgen Antagonists
Limits:
Animals
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2007
Type:
Article
Affiliation country:
United States