Structure activity relationship of some 2,3-diaryl-2H-1-benzopyrans to their anti-implantation, estrogenic and antiestrogenic activities in rat

Abstract

In an endeavour to develop potent anti-implantation agents, a new antiestrogen, CDRI 85/287 (2-(4-2-piperidinoethoxy)phenyl-3-phenyl(2H)benzo(b)pyran), virtually devoid of agonistic activity, was identified. The present study deals with anti-implantation and estrogen agonistic-antagonistic activities of four structural analogues of 85/287. Results show that none of the compounds induced vaginal cornification, even at doses as high as 2.5 mg/kg. Compounds having p-hydroxyphenyl group at position-3 or hydroxy group at position-7 showed better estrogen receptor affinity (6.6 and 25.3% E2) as well as antiestogenic activity. When 3-p-hydroxyphenyl was replaced by 3-p-methoxyphenyl, a marked reduction in the receptor affinity was observed. However, this compound was relatively more potent as an anti-implantation agent, possibly due to its conversion to hydroxylated metabolite in vivo. The provision of aminoethoxy side chain at para-position and a shift in the piperidinoethoxy side chain from position-4 to position-2 in these molecules resulted in a decrease in estrogenicity and increase in antagonistic property. Results are discussed with regard to molecular configuration, relative binding affinity of these compounds to their biological profile.