Development of novel NK3 receptor antagonists with reduced environmental impact. Issue 16 (15th August 2016)

• Record Type: Journal Article
• Authors: Yamamoto, Koki; Okazaki, Shiho; Ohno, Hiroaki; Matsuda, Fuko; Ohkura, Satoshi; Maeda, Kei-ichiro; Fujii, Nobutaka; Oishi, Shinya
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 16(2016)
• Page Start: 3494
• Page End: 3500
• Publication Date: 2016-08-15
• Subjects: GnRH gonadotropin-releasing hormone -- NKB neurokinin B -- NK3R neurokinin-3 receptor -- PCOS polycystic ovary syndrome; Environmental toxicity -- GnRH -- Neurokinin B -- NK3 receptor -- Talnetant; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.05.054
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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-mercaptoquinoline2f exhibited a comparable biological activity to that of the parent talnetant. Additionally, compound2f was converted into the disulfide3f or isothiazolone8 by air-oxidation, both of which showed no binding affinity to NK3R.