Development of novel NK3 receptor antagonists with reduced environmental impact

Bioorg Med Chem. 2016 Aug 15;24(16):3494-500. doi: 10.1016/j.bmc.2016.05.054. Epub 2016 May 28.

Abstract

The neurokinin B (NKB)-neurokinin-3 receptor (NK3R) signaling positively regulates the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. The NK3R-selective antagonists may suppress the reproductive functions of mammals. For development of novel NK3R antagonists with reduced environmental toxicity, a structure-activity relationship study of an NK3R antagonist, talnetant, was carried out. Among several talnetant derivatives with labile functional groups in the natural environment, 3-mercaptoquinoline 2f exhibited a comparable biological activity to that of the parent talnetant. Additionally, compound 2f was converted into the disulfide 3f or isothiazolone 8 by air-oxidation, both of which showed no binding affinity to NK3R.

Keywords: Environmental toxicity; GnRH; NK3 receptor; Neurokinin B; Talnetant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Environmental Pollutants
  • Humans
  • Receptors, Neurokinin-3 / antagonists & inhibitors*

Substances

  • Environmental Pollutants
  • Receptors, Neurokinin-3