A novel synthesis of 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones as potent, stable GnRH receptor antagonists.
A novel synthesis of 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones as potent, stable GnRH receptor antagonists.
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DOI：
10.1016/s0960-894x(02)00745-x
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发表时间：
2002-12
影响因子：
2.7
通讯作者：
F. Tucci;Yun-fei Zhu;Zhiqian Guo;T. Gross;Patrick J. Connors;R. Struthers;Greg J. Reinhart;Xiaochuan Wang;J. Saunders;Chen Chen-Chen
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文献类型：
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作者：
F. Tucci;Yun-fei Zhu;Zhiqian Guo;T. Gross;Patrick J. Connors;R. Struthers;Greg J. Reinhart;Xiaochuan Wang;J. Saunders;Chen Chen-Chen
A new class of small molecule GnRH antagonists, the 7-aryl-8-fluoro-pyrrolo[1,2-a]pyrimid-4-ones, was designed and a novel synthesis for these compounds was developed. The synthesis utilizes a base-catalyzed intramolecular cyclization of fluoromethyl pyrimidone 5 to generate the bicyclic core. Amongst the compounds synthesized, we discovered some highly potent GnRH receptor antagonists (e.g., 12, Ki=9 nM), which showed enhanced stability towards acidic physiological conditions compared to the des-fluoro analogues.
