[Relation of the progestagenic activity and conformation of the 17beta-acetyl side chain in the D'6-pentarane series].
The synthesis of 2' beta-methyl-16 alpha,17 alpha-cyclohexanoprogesterone and its MM2 conformational analysis have been performed. The acetyl side chain was shown to have an unusual conformation with the torsion angle C13-C17-C20-O20 being -32.1 degrees. This conformation is by 5.4 kJ.mol-1 more stable than the usual one with the torsion angle 130.3 degrees. 2' beta-Methyl-16 alpha,17 alpha-cyclohexanoprogesterone proved to be inactive as a progestogen (pregnancy maintenance and McPhail tests). The lack of the activity may be due to the additional methyl group in D'-ring causing a change of the conformation of the 17 beta-acetyl side chain, thus hindering the formation of the conformation necessary for binding to the progesterone receptor.
Kamernitskiĭ
A V
AV
Levina
I S
IS
Kulikova
L E
LE
Korkhov
V V
VV
Nikitina
G V
GV
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D008968:Molecular Conformation; D011247:Pregnancy; D011374:Progesterone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D045167:Progesterone Congeners / Q000494:pharmacology; D011817:Rabbits; D013329:Structure-Activity Relationship
D045167:Progesterone Congeners; C057735:2'-methyl-16,17-cyclohexaneprogesterone; D011374:Progesterone
Zavisimost' progestagennogo deĭstviia v riadu pregna-D'6-pentaranov ot konformatsii 17beta-atsetil'noĭ bokovoĭ tsepi.