Discovery and Structural Modification of 1-Phenyl-3-(1-phenylethyl)urea Derivatives as Inhibitors of Complement
(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.
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2574767
- author
- organization
- publishing date
- 2012
- 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 (ACS)
- external identifiers
-
- wos:000302591000012
- scopus:84859754252
- pmid:24900471
- 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
- 2016-04-01 13:30:06
- date last changed
- 2022-02-19 05:50:07
@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}}, keywords = {{high-throughput screening; structural modification; complement; inhibitors; C9}}, language = {{eng}}, number = {{4}}, pages = {{317--321}}, publisher = {{The American Chemical Society (ACS)}}, 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}}, doi = {{10.1021/ml300005w}}, volume = {{3}}, year = {{2012}}, }