Discovery of small-molecule nonpeptide antagonists of nociceptin/orphanin FQ receptor: The studies of design, synthesis, and structure-activity relationships for (4-arylpiperidine substituted-methyl)-[bicyclic (hetero)cycloalkanobenzene] derivatives
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- 作者：Shigeo Hayashi ; Shigeo_Hayashi@nifty.com" class="auth_mail" title="E-mail the corresponding author ; Katsuyo Ohashi ; Sachiko Mihara ; Eriko Nakata ; Chie Emoto ; Atsuko Ohta
- 关键词：Nociceptin/Orphanin FQ (N/OFQ) ; Human NOP (ORL1) receptor selective antagonist ; Multisite interactions with NOP receptor ; Metabolic stability ; HERG potassium ion channel binding ; Prolong QT interval issues
- 刊名：European Journal of Medicinal Chemistry
- 出版年：2016
- 出版时间：23 May 2016
- 年：2016
- 卷：114
- 期：Complete
- 页码：345-364
- 全文大小：3770 K
文摘
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Novel small-molecule NOP receptor antagonists were designed, prepared, and evaluated.
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Compound 15 exhibited high potency and high selectivity as a NOP receptor antagonist.
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Contributing-factors for potency/selectivity of NOP receptor antagonist are suggested.
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Contributing-factors for metabolic stability are suggested.
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Contributing-factors for reducing hERG channel binding affinity are suggested.