Schwarz S, Thieme I, Kosemund D, Undeutsch B, Kummer M, Görls H, Römer W, Kaufmann G, Elger W, Hillisch A, Schneider B
Division of Research and Development, Jenapharm GmbH & Co. KG, Jena, Germany.
Pharmazie. 2001 Nov;56(11):843-9.
To improve the ratio of non-hormonal to hormonal activity, estrogens 3 and 4 were modified at various molecule positions. Isomerization of the 14 alpha,15 alpha-methylene bridge, controlled 3-methoxy group cleavage with respect to the 14 alpha,15 alpha-methylene bridge stereochemistry, reduction of the 8-double bond, and substitution of the oxyfunctionality at C-17 by a methylene and a difluoromethylene moiety were in the focus. As a result of in vivo and in vitro tests, compounds 27 and 29 were selected as potential follow-up candidates of lead 3.
为了提高非激素活性与激素活性的比例，对雌激素3和4的不同分子位置进行了修饰。重点在于14α,15α-亚甲基桥的异构化、相对于14α,15α-亚甲基桥立体化学控制3-甲氧基的裂解、8-双键的还原以及用亚甲基和二氟亚甲基部分取代C-17处的氧官能团。经过体内和体外测试，化合物27和29被选为先导物3的潜在后续候选物。
