N-Aryl-oxazolidin-2-imine Muscle Selective Androgen Receptor Modulators Enhance Potency through Pharmacophore Reorientation

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• 作者：Alexandra A. Nirschl ; Yan Zou ; Stanley R. Krystek ; ; James C. Sutton ; Ligaya M. Simpkins ; John A. Lupisella ; Joyce E. Kuhns ; Ramakrishna Seethala ; Rajasree Golla ; Paul G. Sleph ; Blake C. Beehler ; Gary
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：May 14, 2009
• 年：2009
• 卷：52
• 期：9
• 页码：2794-2798
• 全文大小：200K
• 年卷期：v.52,no.9(May 14, 2009)
• ISSN：1520-4804

文摘

A novel selective androgen receptor modulator (SARM) scaffold was discovered as a byproduct obtained during synthesis of our earlier series of imidazolidin-2-ones. The resulting oxazolidin-2-imines are among the most potent SARMs known, with many analogues exhibiting sub-nM in vitro potency in binding and functional assays. Despite the potential for hydrolytic instability at gut pH, compounds of the present class showed good oral bioavailability and were highly active in a standard rodent pharmacological model.