N-Arylsulfonyl-α-amino carboxamides are potent and selective inhibitors of the chemokine receptor CCR10 that show efficacy in the murine DNFB model of contact hypersensitivity
N-Arylsulfonyl-α-amino carboxamides are potent and selective inhibitors of the chemokine receptor CCR10 that show efficacy in the murine DNFB model of contact hypersensitivity
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DOI：
10.1016/j.bmcl.2016.09.047
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发表时间：
2016-11-01
影响因子：
2.7
通讯作者：
Yu, Yang
中科院分区：
文献类型：
--
作者：
Abeywardane, Asitha;Caviness, Gary;Yu, Yang
Compound 1 ((4-amino-3,5-dichloropheny1)-1-(4-methylpiperidin-1-y1)-4-(2-nitroimidazol-1-y1)-1oxobutane-2-sulfonamido) was discovered to be a 690 nM antagonist of human CCR10 Ca2+ flux. Optimization delivered (2R)-4-(2-cyanopyrrol-1-y1)-S-(1H-indo1-4-y1)-1-(4-methylpiperidin-l-y1)-1oxobutane-2-sulfonamido (eut-22) that is 300 fold more potent a CCR10 antagonist than 1 and eliminates potential toxicity, mutagenicity, and drug-drug-interaction liabilities often associated with nitroaryls and anilines. eut-22 is highly selective over other GPCR's, including a number of other chemokine receptors. Finally, eut-22 is efficacious in the murine DNFB model of contact hypersensitivity. The efficacy of this compound provides further evidence for the role of CCR10 in dermatological inflammatory conditions. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license.
