Identification of an Orally Active Opioid Receptor-like 1 (ORL1) Receptor Antagonist 4-{3-[(2R)-2,3-Dihydroxypropyl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-1-[(1S,3S,4R

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• 作者：Atsushi Satoh ; Takeshi Sagara ; Hiroki Sakoh ; Masaya Hashimoto ; Hiroshi Nakashima ; Tetsuya Kato ; Yasuhiro Goto ; Sayaka Mizutani ; Tomoko Azuma-Kanoh ; Takeshi Tani ; Shoki Okuda ; Osamu Okamoto ; Satoshi Oz
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：July 23, 2009
• 年：2009
• 卷：52
• 期：14
• 页码：4091-4094
• 全文大小：689K
• 年卷期：v.52,no.14(July 23, 2009)
• ISSN：1520-4804

文摘

Our efforts to optimize prototype opioid receptor-like 1 (ORL1) antagonist 1 led to the discovery of 4-{3-[(2R)-2,3-dihydroxypropyl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-1-[(1S,3S,4R)-spiro[bicyclo[2.2.1]heptane-2,1′-cyclopropan]-3-ylmethyl]piperidine 10. 10 showed potent ORL1 antagonistic activity, excellent selectivity over other opioid receptors, and in vivo efficacy after oral dosing. Currently clinical trials of 10 are underway.