Potent, Selective, and CNS-Penetrant Tetrasubstituted Cyclopropane Class Ila Histone Deacetylase (HDAC) Inhibitors

被引：41
作者：
Luckhurst, Christopher A. [1 ]
Breccia, Perla [1 ]
Stott, Andrew J. [1 ]
Aziz, Omar [1 ]
Birch, Helen L. [1 ]
Buerli, Roland W. [1 ]
Hughes, Samantha J. [1 ]
Jarvis, Rebecca E. [1 ]
Lamers, Marieke [1 ]
Leonard, Philip M. [1 ]
Matthews, Kim L. [1 ]
McAllister, George [1 ]
Pollack, Scott [1 ]
Saville-Stones, Elizabeth [1 ]
Wishart, Grant [1 ]
Yates, Dawn [1 ]
Dominguez, Celia [2 ]
机构：
[1] BioFocus, Chesterford Res Pk, Saffron Walden CB10 1XL, Essex, England
[2] CHDI Management CHDI Fdn Inc, 6080 Ctr Dr,Suite 100, Los Angeles, CA 90045 USA
来源：
ACS MEDICINAL CHEMISTRY LETTERS | 2016年 / 7卷 / 01期
关键词：
Class IIa HDAC inhibitors; hydroxamic acid; CNS exposure; tetrasubstituted cyclopropane; cyclopropanation; Huntington's disease;
D O I：
10.1021/acsmedchemlett.5b00302
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Potent and selective class Ha HDAC tetrasubstituted cyclopropane hydroxamic acid inhibitors were identified with high oral bioavailability that exhibited good brain and muscle exposure. Compound 14 displayed suitable properties for assessment of the impact of class Ha HDAC catalytic site inhibition in preclinical disease models.
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收藏
页码：34 / 39
页数：6
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