Structure activity relationship of some 2,3-diaryl-2H-1-benzopyrans to their anti-implantation, estrogenic and antiestrogenic activities in rat.
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.
Dhar
J D
JD
Division of Endocrinology, Central Drug Research Institute, Lucknow, India.
Dwivedi
A
A
Srivastava
A
A
Setty
B S
BS
D000818:Animals; D001578:Benzopyrans / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D010064:Embryo Implantation / Q000187:drug effects*; D004958:Estradiol / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D013329:Structure-Activity Relationship; D014621:Vagina / Q000187:drug effects / Q000502:physiology
D001578:Benzopyrans; D004965:Estrogen Antagonists; D010880:Piperidines; D011960:Receptors, Estrogen; C066624:CDRI 85-287; D004958:Estradiol