title: 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.
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003270:Contraceptive Agents / Q000494:pharmacology; D004338:Drug Combinations; D005260:Female; D006168:Guinea Pigs; D008656:Mestranol / Q000494:pharmacology; D008968:Molecular Conformation; D010060:Ovulation / Q000187:drug effects; D011247:Pregnancy; D011255:Pregnancy Maintenance / Q000187:drug effects; D011374:Progesterone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D045167:Progesterone Congeners / Q000494:pharmacology*; D011817:Rabbits; D011980:Receptors, Progesterone / Q000378:metabolism; D013329:Structure-Activity Relationship; D014599:Uterus / Q000378:metabolism
chemical_list: D003270:Contraceptive Agents; D004338:Drug Combinations; D045167:Progesterone Congeners; D011980:Receptors, Progesterone; D011374:Progesterone; D008656:Mestranol