Academic Journal
Structure-based design, synthesis and biological evaluation of novel β-secretase inhibitors containing a pyrazole or thiazole moiety as the P3 ligand
| العنوان: | Structure-based design, synthesis and biological evaluation of novel β-secretase inhibitors containing a pyrazole or thiazole moiety as the P3 ligand |
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| المؤلفون: | Ghosh, Arun K., Yen, Yu Chen, Xu, Xiaoming, Huang, Xiangping, Devasamudram, Thippeswamy, Bilcer, Geoffrey, Lei, Hui, Koelsch, Gerald, Mesecar, Andrew D., Tang, Jordan, BRINDISI, MARGHERITA |
| المساهمون: | Ghosh, Arun K., Brindisi, Margherita, Yen, Yu Chen, Xu, Xiaoming, Huang, Xiangping, Devasamudram, Thippeswamy, Bilcer, Geoffrey, Lei, Hui, Koelsch, Gerald, Mesecar, Andrew D., Tang, Jordan |
| سنة النشر: | 2015 |
| المجموعة: | Università degli Studi di Siena: USiena air |
| مصطلحات موضوعية: | Alzheimer's disease, BACE-1, Memapsin 2, Protease inhibitor, β-secretase, Amyloid Precursor Protein Secretase, Binding Site, Catalytic Domain, Crystallography, X-Ray, Kinetic, Ligand, Molecular Dynamics Simulation, Protein Binding, Pyrazole, Structure-Activity Relationship, Thiazole, Drug Design, Biochemistry, Molecular Medicine, Molecular Biology, Drug Discovery3003 Pharmaceutical Science, Clinical Biochemistry, Organic Chemistry |
| Time: | 3003 |
| الوصف: | We describe structure-based design, synthesis, and biological evaluation of a series of novel inhibitors bearing a pyrazole (compounds 3a-h) or a thiazole moiety (compounds 4a-e) as the P3 ligand. We have also explored Boc-β-amino-l-alanine as a novel P2 ligand. A number of inhibitors have displayed β-secretase inhibitory potency. Inhibitor 4c has shown potent BACE1 inhibitory activity, K i = 0.25 nM, cellular EC 50 of 194 nM, and displayed good selectivity over BACE2. A model of 4c was created based upon the X-ray structure of 2-bound β-secretase which revealed critical interactions in the active site. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/25537272; info:eu-repo/semantics/altIdentifier/wos/WOS:000347901700047; volume:25; issue:3; firstpage:668; lastpage:672; numberofpages:5; journal:BIOORGANIC & MEDICINAL CHEMISTRY LETTERS; http://hdl.handle.net/11365/1001169; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84920717227; http://www.journals.elsevier.com/bioorganic-and-medicinal-chemistry-letters/ |
| DOI: | 10.1016/j.bmcl.2014.11.087 |
| الاتاحة: | http://hdl.handle.net/11365/1001169 https://doi.org/10.1016/j.bmcl.2014.11.087 http://www.journals.elsevier.com/bioorganic-and-medicinal-chemistry-letters/ |
| رقم الانضمام: | edsbas.E0E369 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.bmcl.2014.11.087 |
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