Novel non-steroidal/non-anilide type androgen antagonists: discovery of 4-substituted pyrrole-2-carboxamides as a new scaffold for androgen receptor ligands.
Novel non-steroidal/non-anilide type androgen antagonists: discovery of 4-substituted pyrrole-2-carboxamides as a new scaffold for androgen receptor ligands.
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DOI：
10.1016/j.bmc.2005.02.019
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发表时间：
2005-04
影响因子：
3.5
通讯作者：
Ken-ichi Wakabayashi;H. Miyachi;Y. Hashimoto;Aya Tanatani
中科院分区：
文献类型：
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作者：
Ken-ichi Wakabayashi;H. Miyachi;Y. Hashimoto;Aya Tanatani
我们设计并合成了新的吡咯-2-羧酰胺衍生物作为雄激素拮抗剂。在吡咯环4位含有苯胺或苯胺的化合物10和13具有中等的雄激素拮抗活性，抑制盐野癌细胞（SC-3）的雄激素依赖性生长。通过对化合物13的构效关系的研究，得到了一种强效雄激素拮抗剂36，其对雄激素核受体（AR）的亲和力高于氟他胺(4)。因此，吡咯-2-羧酰胺是开发AR拮抗剂的新支架。
We designed and synthesized novel pyrrole-2-carboxamide derivatives as androgen antagonists. Compounds 10 and 13 bearing benzylamine or aniline at the 4-position of the pyrrole ring showed moderate androgen antagonistic activity, and inhibited the androgen-dependent growth of Shionogi carcinoma cells (SC-3). Study of the structure–activity relationships of compound 13 led to a potent androgen antagonist 36, which has higher affinity than flutamide (4) for androgen nuclear receptor (AR). Thus, pyrrole-2-carboxamide is a new scaffold for developing AR antagonists.