Development of novel NK3 receptor antagonists with reduced environmental impact

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• 作者：Koki Yamamoto^a ; Shiho Okazaki^a ; Hiroaki Ohno^a ; Fuko Matsuda^b ; ^c ; Satoshi Ohkura^b ; Kei-ichiro Maeda^c ; Nobutaka Fujii^a ; Shinya Oishi^a ; ^{soishi@pharm.kyoto-u.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：GnRH ; gonadotropin-releasing hormone ; NKB ; neurokinin B ; NK3R ; neurokinin-3 receptor ; PCOS ; polycystic ovary syndrome
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：15 August 2016
• 年：2016
• 卷：24
• 期：16
• 页码：3494-3500
• 全文大小：975 K

文摘

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.