Discovery and Structural Modification of 1-Phenyl-3-(1-phenylethyl)urea Derivatives as Inhibitors of Complement.
Discovery and Structural Modification of 1-Phenyl-3-(1-phenylethyl)urea Derivatives as Inhibitors of Complement.
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DOI：
10.1021/ml300005w
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发表时间：
2012-02
影响因子：
4.2
通讯作者：
Mei Zhang;Xiao-ying Yang;Wei Tang;T. Groeneveld;Pei-lan He;Feng-hua Zhu;Jia Li;Wei Lu;A. Blom;Jian-Ping Zuo;F. Nan
中科院分区：
文献类型：
--
作者：
Mei Zhang;Xiao-ying Yang;Wei Tang;T. Groeneveld;Pei-lan He;Feng-hua Zhu;Jia Li;Wei Lu;A. Blom;Jian-Ping Zuo;F. Nan
A series of 1-phenyl-3-(1-phenylethyl)urea derivatives were identified as novel and potent complement inhibitors through structural modification of the original compound from high-throughput screening. Various analogues (7 and 13-15) were synthesized and identified as complement inhibitors, with the introduction of a five- or six-carbon chain (7c, 7d, 7k, 7l, and 7o) greatly improving their activity. Optimized compound 7l has an excellent inhibition activity with IC50 values as low as 13 nM. We demonstrated that the compound 7l inhibited C9 deposition through the classical, the lectin, and the alternative pathways but had no influence on C3 and C4 depositions.
