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

Zhang, Mei; Yang, Xiao-Ying; Tang, Wei; Groeneveld, Tom LU ; He, Pei-Lan; Zhu, Feng-Hua; Li, Jia; Lu, Wei; Blom, Anna LU and Zuo, Jian-Ping, et al. (2012) In ACS Medicinal Chemistry Letters 3(4). p.317-321
Abstract
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, 7I, and 7o) greatly improving their activity. Optimized compound 7I has an excellent inhibition activity with IC50 values as low as 13 nM. We demonstrated that the compound 7I inhibited C9 deposition through the classical, the lectin, and the alternative pathways but had no influence on C3 and C4 depositions.
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organization
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type
Contribution to journal
publication status
published
subject
keywords
high-throughput screening, structural modification, complement, inhibitors, C9
in
ACS Medicinal Chemistry Letters
volume
3
issue
4
pages
317 - 321
publisher
The American Chemical Society
external identifiers
  • wos:000302591000012
  • scopus:84859754252
ISSN
1948-5875
DOI
10.1021/ml300005w
language
English
LU publication?
yes
id
89bcd52f-77be-420f-b93b-434379f5c509 (old id 2574767)
date added to LUP
2012-06-01 08:57:40
date last changed
2017-11-05 03:58:09
@article{89bcd52f-77be-420f-b93b-434379f5c509,
  abstract     = {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, 7I, and 7o) greatly improving their activity. Optimized compound 7I has an excellent inhibition activity with IC50 values as low as 13 nM. We demonstrated that the compound 7I inhibited C9 deposition through the classical, the lectin, and the alternative pathways but had no influence on C3 and C4 depositions.},
  author       = {Zhang, Mei and Yang, Xiao-Ying and Tang, Wei and Groeneveld, Tom and He, Pei-Lan and Zhu, Feng-Hua and Li, Jia and Lu, Wei and Blom, Anna and Zuo, Jian-Ping and Nan, Fa-Jun},
  issn         = {1948-5875},
  keyword      = {high-throughput screening,structural modification,complement,inhibitors,C9},
  language     = {eng},
  number       = {4},
  pages        = {317--321},
  publisher    = {The American Chemical Society},
  series       = {ACS Medicinal Chemistry Letters},
  title        = {Discovery and Structural Modification of 1-Phenyl-3-(1-phenylethyl)urea Derivatives as Inhibitors of Complement},
  url          = {http://dx.doi.org/10.1021/ml300005w},
  volume       = {3},
  year         = {2012},
}