Title |
Inhibitors of Alzheimer’s BACE-1 with 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridine structure
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Published in |
Archives of Pharmacal Research, April 2014
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DOI | 10.1007/s12272-014-0401-x |
Pubmed ID | |
Authors |
Ramin Miri, Omidreza Firuzi, Nima Razzaghi-Asl, Katayoun Javidnia, Najmeh Edraki |
Abstract |
β-site amyloid precursor protein cleaving enzyme (BACE-1) is a validated target for Alzheimer therapy due to its distinctive role in pathogenesis of AD. In the present contribution, a series of new 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridine structures were synthesized as BACE-1 inhibitors (6a-6n). In vitro BACE-1 inhibitory activities were determined by enzymatic fluorescence resonance energy transfer assay. Synthesized dihydropyridine (DHP) analogues exhibited weak to good inhibitory activities while 6i, 6n and 6a were found to be the most potent molecules with 83.76, 79.45 and 72.47 % BACE-1 inhibition at 10 μM, respectively. Structure binding/activity relationship elucidations revealed that superior BACE-1 inhibitory activities were observed for DHP derivatives bearing fused/non-fused thiazole groups and particularly 3,5-bis-N-(6-ethoxy-2-benzothiazolyl) moiety. Binding maps showed that enhanced activity may be attributed to the additional H-bond and hydrophobic interactions with S2-S3 subpockets of BACE-1. |
X Demographics
Geographical breakdown
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Unknown | 1 | 100% |
Demographic breakdown
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Members of the public | 1 | 100% |
Mendeley readers
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Country | Count | As % |
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United Kingdom | 1 | 5% |
Unknown | 20 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
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Other | 3 | 14% |
Student > Doctoral Student | 3 | 14% |
Researcher | 3 | 14% |
Student > Master | 3 | 14% |
Student > Ph. D. Student | 2 | 10% |
Other | 3 | 14% |
Unknown | 4 | 19% |
Readers by discipline | Count | As % |
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Chemistry | 9 | 43% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 10% |
Physics and Astronomy | 1 | 5% |
Agricultural and Biological Sciences | 1 | 5% |
Medicine and Dentistry | 1 | 5% |
Other | 1 | 5% |
Unknown | 6 | 29% |