Center for Organic and Medicinal Chemistry, Research Triangle Institute , P.O. Box 12194, Research Triangle Park, North Carolina 27709, United States.
J Med Chem. 2014 Jun 26;57(12):5318-32. doi: 10.1021/jm5003843. Epub 2014 Jun 5.
Compounds active at neurotensin receptors (NTS1 and NTS2) exert analgesic effects on different types of nociceptive modalities, including thermal, mechanical, and chemical stimuli. The NTS2 preferring peptide JMV-431 (2) and the NTS2 selective nonpeptide compound levocabastine (6) have been shown to be effective in relieving the pain associated with peripheral neuropathies. With the aim of identifying novel nonpeptide compounds selective for NTS2, we examined analogues of SR48692 (5a) using a FLIPR calcium assay in CHO cells stably expressing rat NTS2. This led to the discovery of the NTS2 selective nonpeptide compound 1-({[1-(4-fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)cyclohexane carboxylic acid (NTRC-739, 7b) starting from the nonselective compound 5a.
作用于神经降压素受体（NTS1 和 NTS2）的化合物对不同类型的伤害性感觉模式（包括热、机械和化学刺激）具有镇痛作用。NTS2 偏爱肽 JMV-431（2）和 NTS2 选择性非肽化合物左卡巴斯汀（6）已被证明可有效缓解周围神经病变引起的疼痛。为了鉴定新型 NTS2 选择性非肽化合物，我们使用在稳定表达大鼠 NTS2 的 CHO 细胞中进行的 FLIPR 钙测定法检查了 SR48692（5a）的类似物。这导致从非选择性化合物 5a 出发发现了 NTS2 选择性非肽化合物 1-({[1-(4-氟苯基)-5-(2-甲氧基苯基)-1H-吡唑-3-基]羰基}氨基)环己烷羧酸（NTRC-739，7b）。
Zotero 插件
