Recent advances in small molecule gonadotrophin-releasing hormone receptor antagonists

Targeting the gonadotrophin-releasing hormone (GnRH) receptor for treatment of a variety of reproductive hormone-dependent diseases has yielded great success so far, with the use of peptide agonists. However, based on the current understanding of GnRH receptor biology, peptide agonists inevitably cause some side effects, such as the ‘flare’ effect and delayed action. By contrast, peptide or small molecule GnRH receptor antagonists should be devoid of the above-mentioned side effects. Furthermore, a small molecule antagonist is more preferable than a peptide antagonist because it also provides the possibility of oral administration, therefore allowing dose flexibility and better patient acceptance. Thus, it is not surprising to see that many patent applications on small molecule GnRH receptor antagonists have emerged over the last 10 years. This review summarises the patent applications of small molecule human GnRH receptor antagonists from 1994 to August 2003. If available, the biological data associated with patent structures are also cited from publications.