title

مهارکنندگان آنزیم بتا-سکرتاز با ساختار 3و5-بیس- N- (آریل/هتروآریل) کارباموئیل-4-آریل 1و4-دی هیدروپیریدین

میری, رامین and فیروزی, امیدرضا and رزاقی اصل, نیما and جاویدنیا, کتایون and ادراکی, نجمه (1394) مهارکنندگان آنزیم بتا-سکرتاز با ساختار 3و5-بیس- N- (آریل/هتروآریل) کارباموئیل-4-آریل 1و4-دی هیدروپیریدین. Archives of Pharmacal Research ــ 38 (4). pp. 456-469. شاپا 0253-6269

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Official URL: http://link.springer.com/article/10.1007%2Fs12272-...


Title

Inhibitors of Alzheimer's BACE-1 with 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridine structure

English Abstract

b-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 lM, 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.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :رامین میری
نویسنده :امیدرضا فیروزی
نویسنده مسئول :نیما رزاقی اصل
نویسنده :کتایون جاویدنیا
نویسنده :نجمه ادراکی
Additional Information:Impact Factor : (2015) 2.490 Indexed in:ISI, PubMed/Medline, SCOPUS, EMBASE, Chemical Abstracts Service (CAS), Google Scholar, CSA, CAB International, Academic OneFile, Biological Abstracts, BIOSIS, CAB Abstracts, Current Contents/ Life Sciences, Expanded Academic, Global Health, International Pharmaceutical Abstracts, OCLC, Reaxys, SCImago, Summon by ProQuest
کلیدواژه ها (انگلیسی):Alzheimer, BACE-1, Inhibition, Dihydropyridine
Subjects:QV pharmacology > QV 744 Medicinal Chemistry
Divisions:School of Pharmacy > Department of Medicinal Chemistry
ID Code:5392
Deposited By: Dr Nima Razzaghi-Asl
Deposited On:16 Jan 1394 03:18
Last Modified:12 Dec 1396 09:03

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