Evestra, Inc., San Antonio, TX, USA.
Steroids. 2013 Feb;78(2):255-67. doi: 10.1016/j.steroids.2012.09.010. Epub 2012 Nov 21.
A series of antiprogestins have been synthesized by partially fluorinating the steroid molecule in positions relevant for receptor binding. By introducing fluorine at the exo-methylene of the 17 spirofuran ring, we obtained partial agonists (mesoprogestins) with significant applications for antiproliferative and antiovulatory treatment strategies in gynecological therapy such as uterine fibroids, endometriosis and heavy menstrual bleeding. Compared to the standard drug RU486, our synthesized compounds exhibited considerable dissociation between antiprogestational and antiglucocorticoid PR receptors. Furthermore, our studies have shown that pure antiprogestins can be generated by partially fluorinating the 17 propenyl and propynl group or by substituting the 4' acetyl phenyl group in the 11 position using trifluromethyl group.
已经通过在与受体结合相关的位置部分氟化甾体分子来合成一系列抗孕激素。通过在 17 螺环呋喃环的亚甲烯基处引入氟原子，我们得到了具有显著应用前景的部分激动剂（中孕激素），可用于妇科治疗中的抗增殖和抗排卵治疗策略，例如子宫肌瘤、子宫内膜异位症和月经过多。与标准药物 RU486 相比，我们合成的化合物在抗孕激素和抗糖皮质激素 PR 受体之间表现出相当大的分离。此外，我们的研究表明，通过部分氟化 17 丙烯基和丙炔基基团，或通过用三氟甲基取代 11 位的 4'乙酰苯基基团，可以生成纯的抗孕激素。
