Synthesis and in vivo evaluation of 11-substituted estradiol derivatives as anti-implantation agents.
Synthesis of 11-substituted estradiol derivatives (12-17) has been carried out by the Grignard reaction with alkyl, allyl, and benzyl halides on 17beta-hydroxy-3-methoxy-11-oxo-estra-1,3,5(10),8(9)-tetraene (10). The novel compounds (10 and 12-17) were evaluated for their preliminary post-coital contraceptive (anti-implantation) activity in Sprague-Dawley rats. The tested compounds were administered orally and showed significant anti-implantation activity. Compound 13 is the most potent compound in the series which showed 100% contraceptive efficacy at 1.25 mg kg(-1).
Dwivedy
Indra
I
Medicinal and Process Chemistry Division, Central Drug Research Institute, PO Box 173, Lucknow 226001, India.
Gupta
Atul
A
Grover
Arvinder
A
Srivastava
Vandana
V
Singh
Man Mohan
MM
Ray
Suprabhat
S
D000284:Administration, Oral; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003270:Contraceptive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003281:Contraceptives, Postcoital / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D010064:Embryo Implantation / Q000187:drug effects*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D008956:Models, Chemical; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature; D016896:Treatment Outcome
D003270:Contraceptive Agents; D003281:Contraceptives, Postcoital; D004958:Estradiol