Development of novel NK3 receptor antagonists with reduced environmental impact.
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Yamamoto K, Okazaki S, Ohno H, Matsuda F, Ohkura S, Maeda K, Fujii N, Oishi S
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.
- PubMed ID
- 27298001 [ View in PubMed]
- 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.