Syntheses and bioevaluation of substituted dihydropyridines for pregnancy-interceptive activity in hamsters.
A number of 2,6-dimethyl-3,5-bis(methoxycarbonyl)-4-substituted-1,4- dihydropyridines were synthesized and evaluated for pregnancy-interceptive activity in mated hamsters. Out of 24 compounds, 12, 15, 21, 22, 28, and 34 caused a marked reduction in the number of implantations when administered on days 3-8 postcoitum. In an in vitro competition assay, none of the compounds exhibited noticeable binding affinity for uterine progesterone receptors. The results reported here have helped to identify new leads for developing pregnancy-interceptive agents and the active compounds do not seem to elicit their interceptive effect through receptor-mediated inhibition of progesterone action in hamster uterus.
Mukherjee
A
A
Medicinal Chemistry and Endocrinology Division, Central Drug Research Institute, Lucknow, India.
Akhtar
M S
MS
Sharma
V L
VL
Seth
M
M
Bhaduri
A P
AP
Agnihotri
A
A
Mehrotra
P K
PK
Kamboj
V P
VP
D000019:Abortifacient Agents / Q000138:chemical synthesis*; D000818:Animals; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D008647:Mesocricetus; D015394:Molecular Structure; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D011817:Rabbits; D011980:Receptors, Progesterone / Q000187:drug effects* / Q000378:metabolism; D012016:Reference Values; D013329:Structure-Activity Relationship; D014599:Uterus / Q000378:metabolism*
D000019:Abortifacient Agents; D004095:Dihydropyridines; D011980:Receptors, Progesterone; D011374:Progesterone