四氢异喹啉类化合物的合成及构效关系研究作为 Rev-erbα 激动剂。
Synthesis and SAR of tetrahydroisoquinolines as Rev-erbα agonists.
机构信息
Department of Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA.
出版信息
Bioorg Med Chem Lett. 2012 Jun 1;22(11):3739-42. doi: 10.1016/j.bmcl.2012.04.023. Epub 2012 Apr 13.
Abstract
The design and synthesis of a novel series of Rev-erbα agonists is described. The development and optimization of the tetrahydroisoquinoline series was carried out from an earlier acyclic series of Rev-erbα agonists. Through the optimization of the scaffold 1, several potent compounds with good in vivo profiles were discovered.
摘要
本文描述了一种新型 Rev-erbα 激动剂的设计和合成。从早期的非环系列 Rev-erbα 激动剂出发，对四氢异喹啉系列进行了开发和优化。通过对骨架 1 的优化，发现了几种具有良好体内特性的有效化合物。
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本文引用的文献
1
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Chem Biol. 2012 Jan 27;19(1):51-9. doi: 10.1016/j.chembiol.2011.12.011.
2
Nuclear hormone receptors as therapeutic targets.作为治疗靶点的核激素受体
Contrib Nephrol. 2011;170:209-216. doi: 10.1159/000325668. Epub 2011 Jun 9.
3
The REV-ERBs and RORs: molecular links between circadian rhythms and lipid homeostasis.REV-ERBs 和 RORs：昼夜节律与脂质动态平衡之间的分子联系。
Future Med Chem. 2011 Apr;3(5):623-38. doi: 10.4155/fmc.11.9.
4
A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism.组蛋白去乙酰化酶 3 调控的生物钟节律控制肝脏脂质代谢。
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5
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