β-arrestin 偏向性、口服生物利用度和中枢神经系统穿透性神经降压素受体 1（NTR1）变构调节剂的发现。
Discovery of β-Arrestin Biased, Orally Bioavailable, and CNS Penetrant Neurotensin Receptor 1 (NTR1) Allosteric Modulators.
机构信息
Conrad Prebys Center for Chemical Genomics , Sanford Burnham Prebys Medical Discovery Institute , La Jolla , California 92037 , United States.
Duke University Medical Center , Durham , North Carolina 27709 , United States.
出版信息
J Med Chem. 2019 Sep 12;62(17):8357-8363. doi: 10.1021/acs.jmedchem.9b00340. Epub 2019 Aug 20.
Abstract
Neurotensin receptor 1 (NTR1) is a G protein coupled receptor that is widely expressed throughout the central nervous system where it acts as a neuromodulator. Neurotensin receptors have been implicated in a wide variety of CNS disorders, but despite extensive efforts to develop small molecule ligands there are few reports of such compounds. Herein we describe the optimization of a quinazoline based lead to give (SBI-553), a potent and brain penetrant NTR1 allosteric modulator.
摘要
神经降压素受体 1（NTR1）是一种 G 蛋白偶联受体，广泛表达于中枢神经系统，作为一种神经调质发挥作用。神经降压素受体与多种中枢神经系统疾病有关，但尽管人们努力开发小分子配体，但此类化合物的报道很少。本文描述了基于喹唑啉的先导化合物的优化，得到了一种强效且可穿透血脑屏障的 NTR1 变构调节剂（SBI-553）。
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