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Peptidomimetic GnRH receptor antagonists for the treatment of reproductive and proliferative diseases

Gonadotropin releasing hormone (GnRH), also known as luteinising hormone releasing hormone (LHRH), is a decapeptide released from the hypothalamus that binds to the G-protein-coupled GnRH receptor located on the pituitary gland. This receptor plays an important role in human reproduction, reproductive and proliferative diseases such as endometriosis, uterine fibroids, precocious puberty, prostate/breast/ovarian cancers and prostatic hyperplasia, conditions that can be potentially treated by GnRH receptor agonists or antagonists. Peptidic GnRH receptor agonists and antagonists have long been used for the treatment of several disorders, but the problems associated with peptides have encouraged the research and development of orally bioavailable peptidomimetic small-molecule GnRH receptor antagonists. This review summarises the patent literature during 2001 – 2005 on small-molecule GnRH receptor antagonists.