American Chemical Society
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Discovery and Structural Modification of 1-Phenyl-3-(1-phenylethyl)urea Derivatives as Inhibitors of Complement

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journal contribution
posted on 2016-02-21, 14:48 authored by Mei Zhang, Xiao-Ying Yang, Wei Tang, Tom W. L. Groeneveld, Pei-Lan He, Feng-Hua Zhu, Jia Li, Wei Lu, Anna M. Blom, Jian-Ping Zuo, Fa-Jun 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 1315) 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.