Non Steroidal Estrogen Antagonists: Current Status and Future Perspectives

The development of compounds that can counteract the biological effects of estrogens has drawn a lot of attention over the last several decades. Such compounds termed as estrogen antagonists or antiestrogens are of considerable interest both in pharmaceutical industry as well as in academic research groups as potential therapeutic agents. A large number of Non Steroidal molecules belonging to diverse classes such as stilbenes, ethanes, 2-phenyl indoles, phenylindenes, benzofurans, benzothiophenes, triarylethylenes, triarylpropenones and more recently 2,3-diaryl benzopyrans have shown estrogen antagonistic activities. They have found several clinical applications like clomiphene in the treatment of endocrine disorders and due to relative or absolute hormone excess, tamoxifen and its derivatives toremifene, droloxifene, idoxifene are being used to treat hormone dependent cancers chiefly breast cancer, raloxifene, for the prevention and treatment of post menopausal osteoporosis and most importantly ormeloxifene or centchroman as the first nonsteroidal post-coital contraceptive because of its ability to antagonize estrogen action in the uterus by interfering with endogenous hormone during the pre-implantation and post implantation phases of reproduction. The clinical success of these molecules coupled with the novel finding of tissue selectivity exhibited by some recent molecules has once again refocused the attention of chemist and biologists on the development of estrogen hormone antagonists as selective target of tissue specific drugs. Many new nonsteroidal antagonists like EM-800, CP-336156, GW-5638, arzoxifene are in various stages of clinical development as tissue selective estrogen receptor modulators.