Tandem optimization of target activity and elimination of mutagenic potential in a potent series of N-aryl bicyclic hydantoin-based selective androgen receptor modulators
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.
Hamann, Lawrence G.,Manfredi, Mark C.,Sun, Chongqing,Krystek Jr., Stanley R.,Huang, Yanting,Bi, Yingzhi,Augeri, David J.,Wang, Tammy,Zou, Yan,Betebenner, David. A.,Fura, Aberra,Seethala, Ramakrishna,Golla, Rajasree,Kuhns, Joyce E.,Lupisella, John A.,Darienzo, Celia J.,Custer, Laura L.,Price, Jennifer L.,Johnson, James M.,Biller, Scott A.,Zahler, Robert,Ostrowski, Jacek
p. 1860 - 1864
(2008/02/04)
Anthranilonitrile derivatives and related compounds as useful agents for promoting growth, improving feed efficiency, and for increasing the lean meat to fat ratio of warm-blooded animals
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(2008/06/13)
Anthranilonitrile derivatives as useful agents for promoting growth, improving feed efficiency, and for increasing the lean meat to fat ratio of warm-blooded animals
There are provided novel anthranilonitrile derivatives and related compounds which are useful for promoting growth, improving feed efficiency and for increasing the lean meat to fat ratio of warm-blooded animals.
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(2008/06/13)
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