Relationship between structure and mode of action of 16 alpha, 17 alpha-cycloalkanoprogesterones (pregna-D'-pentaranes).

Abstract

A new class of modified progesterones with an additional 16 alpha, 17 alpha-carbocycle (pregna-D'-pentaranes) is obtained. These compounds were found to exhibit a high progestational activity in the Clauberg-McPhail assay and to be active as well in the pregnancy maintenance test in ovariectomized rabbits. Some of the pentaranes displayed a remarkable contraceptive effect in combination with mestranol. X-Ray data were employed for the description of molecular conformations of D'-pentaranes. On this base, their biological responses are considered to be connected with the conformational changes of D and D' rings as well as 17 beta-acetyl side chain. Accordingly, the contraceptive effect of D'3-6-pentaranes is correlated with the value of C(15)-C(16)-C(17)-C(20) torsion angle of the corresponding molecules. The relative binding affinities of some D'6-pentaranes to the progestin receptor were determined and compared with their in vivo biological responses.