| Literature DB >> 20620068 |
Wenhai Huang1, Dan Lv, Haiping Yu, Rong Sheng, Sun Chol Kim, Peng Wu, Kedi Luo, Jia Li, Yongzhou Hu.
Abstract
Dual-target-directed 1,3-diphenylurea derivatives were designed by hybridizing BACE 1 inhibitor 1 with metal chelator LR-90. A database consisted of 1,3-diphenylurea derivatives was built and screened by the pharmacophore model (Hypo 1) of BACE 1 inhibitor. Based on the predicted results, 11 compounds (6a-d, 9a-g) with favorable Fitvalues were selected, synthesized and evaluated for their BACE 1 inhibitory activities, which showed that the predicted results were in good agreement with the experimental values. Besides, the synthesized compounds also displayed the ability to chelate metal ions. The most effective BACE 1 inhibitor 9f (27.85+/-2.46 micromol/L) was selected for further receptor-binding studies, the result of which indicated that an essential hydrogen bonds was formed between the urea group of 9f and the catalytic aspartate Asp228. Copyright (c) 2010 Elsevier Ltd. All rights reserved.Entities:
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Year: 2010 PMID： 20620068 DOI： 10.1016/j.bmc.2010.06.042
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641