Resolution, molecular structure and biological activities of the D- and L-enantiomers of potent anti-implantation agent, DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran.
Compound 1 (DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran, CDRI 85/287) a potent anti-estrogen and anti-implantation agent has been successfully resolved into its pure D- and L-enantiomers. Biological studies showed L-enantiomer to be the active form, exhibiting a fivefold higher receptor affinity for the rat uterine cytosolic estrogen receptor, 100% contraceptive efficacy at 1.3 mg/kg dose in single day schedule and 89% inhibition of estradiol induced increase of uterine weight at its contraceptive dose. The absolute stereochemistry determined by X-ray crystallographic analysis showed that the L-enantiomer has 2R configuration at its asymmetric centre.
Hajela
K
K
Medicinal Chemistry Division, Central Drug Research Institute, Lucknow, India. root@cscdri.ren.nic.in
Pandey
J
J
Dwivedy
A
A
Dhar
J D
JD
Sarkhel
S
S
Maulik
P R
PR
Velumurugan
D
D
D000818:Animals; D001578:Benzopyrans / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D010064:Embryo Implantation / Q000187:drug effects*; D004965:Estrogen Antagonists / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D013237:Stereoisomerism; D014599:Uterus / Q000187:drug effects
D001578:Benzopyrans; D004965:Estrogen Antagonists; D010880:Piperidines; D011960:Receptors, Estrogen; C066624:CDRI 85-287