2. Academic Validation
  3. Development of novel NK3 receptor antagonists with reduced environmental impact

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.
Koki Yamamoto 1,  Shiho Okazaki 1,  Hiroaki Ohno 1,  Fuko Matsuda 2,  Satoshi Ohkura 3,  Kei-Ichiro Maeda 4,  Nobutaka Fujii 1,  Shinya Oishi 5
Affiliations

Affiliations

  • 1 Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
  • 2 Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan; Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
  • 3 Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
  • 4 Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
  • 5 Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: soishi@pharm.kyoto-u.ac.jp.
PMID: 27298001 DOI: 10.1016/j.bmc.2016.05.054
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.

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