伪-Ketoheterocycle inhibitors of fatty acid amide hydrolase: Exploration of conformational constraints in the acyl side chain

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• 作者：Katharine K. Duncan ; Katerina Otrubova ; Dale L. Boger ; ^{boger@scripps.edu" class="auth_mail}
• 关键词：Fatty acid amide hydrolase ; 伪-Ketoheterocycles
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：1 May, 2014
• 年：2014
• 卷：22
• 期：9
• 页码：2763-2770
• 全文大小：1507 K

文摘

A series of 伪-ketooxazoles containing heteroatoms embedded within conformational constraints in the C2 acyl side chain of 2 (OL-135) were synthesized and evaluated as inhibitors of fatty acid amide hydrolase (FAAH). The studies reveal that the installation of a heteroatom (O) in the conformational constraint is achievable, although the potency of these novel derivatives is reduced slightly relative to 2 and the analogous 1,2,3,4-tetrahydronaphthalene series. Interestingly, both enantiomers (R and S) of the candidate inhibitors bearing a chiral center adjacent to the electrophilic carbonyl were found to effectively inhibit FAAH.