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

Abstract

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.