Synthesis and pregnancy-inhibiting activity of 7-substituted androst-5-ene derivatives.
Synthesis of 7-aryl/allyl-substituted androstene derivatives 3a through 3g has been carried out by Grignard reaction on 3 beta,17 beta-diacetoxyandrost-5-en-7-one (2) with aryl/allyl magnesium bromide. Isomeric mixture of products 3b and 3c/3e and 3f/3h was separated by column chromatography. Stereochemical assignment at C-7 has been made on the basis of 13C nuclear magnetic resonance studies and chemical considerations. Compounds 6a and 6b were synthesized by alkylation of compound 5 with beta-(N,N-diethylamino)ethyl chloride hydrochloride and 1-(2-chloroethyl)pyrrolidine hydrochloride, respectively. Compound 3g (isomeric mixture) prevented pregnancy in 60% of rats at 10 mg/kg daily dose administered orally on days 1 to 7 of pregnancy; however, its only isolable 7 beta-hydroxy isomer, 3h, was inactive at this dose.
Grover
A
A
Medicinal Chemistry Division, Central Drug Research Institute, Lucknow, India.
Dwivedy
I
I
Singh
A K
AK
Ray
S
S
Singh
M M
MM
Kamboj
V P
VP
D000736:Androstenes / Q000138:chemical synthesis* / Q000494:pharmacology; D003270:Contraceptive Agents / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy
D000736:Androstenes; D003270:Contraceptive Agents