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Centchroman (INN: Ormeloxifene), a reversible post-coital/weekly oral contraceptive (half-life of about 168 hours), designed and developed at CDRI, Lucknow is the only non-steroidal oral contraceptive in clinical use in the world today. Synthesized in 1967 and completing pre-clinical and clinical studies in 1989, this drug was approved for marketing in 1991, social marketing in 1995 and NFPW in April 2016. It acts by preventing implantation of blastocyst in endometrium. It is the only contraceptive which neither suppresses ovulation nor interferes with the hypothalamic-pituitary-ovarian axis. It has high level of safety and is virtually free from side effects except for a delay in about 8% menstrual cycles which is not confined to any women/cycle. Besides contraception, this SERM is also clinically useful in the management of DUB, mastalgia and fibroadenoma and has promising therapeutic efficacy in a variety of cancers including breast cancer. Due to estrogenic activity, this drug also has anti-osteoporotic and cardioprotective activity. Thus, Centchroman is likely to show other curative and prophylactic activity in a wide range of other disorders.

It is well known that a wide variety of molecules compete for binding to the estrogen receptor and act as estrogens and/or antiestrogens. These molecules such as estradiol, diethylstilbestrol, doisynolic acid, the triarylethylenes, and cyclofenyl apparently share little resemblance which could account for their interaction with a common estrogen binding site. Knowledge of the receptor binding of triarylethylene and cyclofenyl prototypes, in particular, relative to that of the other estrogens is critical for understanding their structure-function relationship. We have carried out a study on the receptor binding specificity of triarylethylene and cyclofenyl prototypes. This study has revealed that these molecular types share considerable resemblance in their receptor binding specificity and differ from estradiol and other similar molecules in some important respects. However, comparison of their substructural binding specificities reveals the possibility that the triarylethylene and estradiol prototypes may interact with at least some common regions of the estrogen binding site. Based on this reasoning the comparative receptor binding of estrogens has been rationalized on the basis of a subsite hypothesis for the estrogen binding site. According to this hypothesis, the composite estrogen binding site is composed of essentially five subsites, and that the structurally different estrogenic prototypes can interact with different set of subsites, and thus differ in their binding orientation. The essential difference in the activity profile of estradiol prototypes and the triarylethylene antiestrogens reveals the possibility of a causal relationship between the binding orientation of a ligand and its activity profile. This model for receptor site can thus serve as a working hypothesis to rationalize the structure-function relationship of estrogens.