Selective oestrogen receptor modulators, pure antioestrogens and related oestrogen receptor ligands

Oestrogen or hormone replacement therapy (HRT) is an effective treatment for postmenopausal women in alleviating disorders associated with lower circulating levels of oestrogens such as hot flushes and osteoporosis. Unfortunately, long-term HRT is associated with an increased risk of breast and endometrial cancers. Consequently, an alternative to traditional HRT has been the use of selective oestrogen receptor modulators (SERMs), which antagonise the oestrogen receptor (ER) in the breast and uterus but at the same time exert beneficial effects on bone. Initially, most of the SERMs had targeted ERα for HRT. After the identification of ERβ, however, speculation grew that ERβ would be an additional exciting target for HRT. This speculation was further fuelled since ERβ was not the dominant ER receptor in the uterus, the key organ to avoid stimulating in HRT. The aim of this review is to summarise the relevant patent literature from January 2000 to June 2003 on SERMs, pure antioestrogens and related ER modulatory ligands, mainly with respect to their chemical scaffolds and broad therapeutic relevance .