N-Aryl-oxazolidin-2-imine Muscle Selective Androgen Receptor Modulators Enhance Potency through Pharmacophore Reorientation
N-Aryl-oxazolidin-2-imine Muscle Selective Androgen Receptor Modulators Enhance Potency through Pharmacophore Reorientation
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DOI：
10.1021/jm801583j
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发表时间：
2009-05-14
影响因子：
7.3
通讯作者：
Hamann, Lawrence G.
中科院分区：
文献类型：
--
作者：
Nirschl, Alexandra A.;Zou, Yan;Hamann, Lawrence G.
一种新的选择性雄激素受体调节剂（SARM）支架被发现作为我们早期系列咪唑烷-2-酮合成过程中获得的副产物。所得的恶唑烷-2-亚胺是已知的最有效的SARM之一，许多类似物在结合和功能测定中表现出亚nM的体外效力。尽管在肠道pH下可能存在水解不稳定性，但本类别的化合物显示出良好的口服生物利用度，并且在标准啮齿动物药理学模型中具有高度活性。
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.