Alkylsulfone-containing trisubstituted cyclohexanes as potent and bioavailable chemokine receptor 2 (CCR2) antagonists.
Alkylsulfone-containing trisubstituted cyclohexanes as potent and bioavailable chemokine receptor 2 (CCR2) antagonists.
复制标题
含有烷基砜的三取代环己烷作为有效且生物可利用的趋化因子受体 2 (CCR2) 拮抗剂。
DOI：
10.1016/j.bmcl.2014.02.013
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发表时间：
2014
影响因子：
2.7
通讯作者：
Carter,PercyH
中科院分区：
文献类型：
--
作者：
Cherney,RobertJ;Mo,Ruowei;Yang,MichaelG;Xiao,Zili;Zhao,Qihong;Mandlekar,Sandhya;Cvijic,MaryEllen;Charo,IsraelF;Barrish,JoelC;Decicco,CarlP;Carter,PercyH
我们描述了新的烷基砜作为有效的CCR2拮抗剂，与我们以前描述的拮抗剂相比，具有降低的hERG通道活性和改善的药代动力学。这些新的烷基砜中的几种具有包括CCR2的功能性拮抗作用、体外微粒体稳定性和口服生物利用度的特征。有了这种改善的概况，我们证明了这些拮抗剂中的两种，2和12，在炎症募集的动物模型中口服有效。
We describe novel alkylsulfones as potent CCR2 antagonists with reduced hERG channel activity and improved pharmacokinetics over our previously described antagonists. Several of these new alkylsulfones have a profile that includes functional antagonism of CCR2, in vitro microsomal stability, and oral bioavailability. With this improved profile, we demonstrate that two of these antagonists,2and12, are orally efficacious in an animal model of inflammatory recruitment.