| Title | 2-Substituted-thio-N-(4-substituted-thiazo1/1H-imidazol-2-yl) acetamides as BACE1 inhibitors: Synthesis, biological evaluation and docking studies |
| Authors | Yan, Gang Hao, Lina Niu, Yan Huang, Wenjie Wang, Wei Xu, Fengrong Liang, Lei Wang, Chao Jin, Hongwei Xu, Ping |
| Affiliation | Peking Univ, Hlth Sci Ctr, Dept Med Chem, Sch Pharmaceut Sci, 38 Xueyuan Rd, Beijing 100191, Peoples R China. Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, 38 Xueyuan Rd, Beijing 100191, Peoples R China. |
| Keywords | Alzheimer's disease BACE-1 inhibitors Docking study BBB Permeability Surface Plasmon Resonance (SPR) PAMPA SS-SECRETASE INHIBITORS STRUCTURE-BASED DESIGN BLOOD-BRAIN-BARRIER IN-VITRO EVALUATION ALZHEIMERS-DISEASE BETA-SECRETASE DRUG DESIGN DERIVATIVES DISCOVERY PROTEASE |
| Issue Date | 2017 |
| Publisher | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY |
| Citation | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY.2017,137,462-475. |
| Abstract | In this work, a series of 2-substituted-thio-N-(4-substituted-thiazol/1H-imidazol-2-yl)acetamide derivatives were developed as beta-secretase (BACE-1) inhibitors. Supported by docking study, a small library of derivatives were designed, synthesized and biologically evaluated in vitro. In addition, the selected compounds were tested with affinity (K-D) towards BACE-1, blood brain barrier (BBB) permeability and cytotoxicity. The studies revealed that the most potent analog 41 (IC50 = 4.6 mu M) with high predicted BBB permeability and low cellular cytotoxicity, could serve as a good lead structure for further optimization. (C) 2017 Elsevier Masson SAS. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/470912 |
| ISSN | 0223-5234 |
| DOI | 10.1016/j.ejmech.2017.06.020 |
| Indexed | SCI(E) |
| Appears in Collections: | 天然药物与仿生药物国家重点实验室 |
