| Literature DB >> 19959359 |
Pawel Nowak1, Derek C Cole, Ann Aulabaugh, Jonathan Bard, Rajiv Chopra, Rebecca Cowling, Kristi Y Fan, Baihua Hu, Steve Jacobsen, Minakshi Jani, Guixan Jin, Mei-Chu Lo, Michael S Malamas, Eric S Manas, Rani Narasimhan, Peter Reinhart, Albert J Robichaud, Joseph R Stock, Joan Subrath, Kristine Svenson, Jim Turner, Erik Wagner, Ping Zhou, John W Ellingboe.
Abstract
8,8-Diphenyl-2,3,4,8-tetrahydroimidazo[1,5-a]pyrimidin-6-amine (1) was identified through HTS, as a weak (micromolar) inhibitor of BACE1. X-Ray crystallographic studies indicate the 2-aminoimidazole ring forms key H-bonding interactions with Asp32 and Asp228 in the catalytic site of BACE1. Lead optimization using structure-based focused libraries led to the identification of low nanomolar BACE1 inhibitors such as 20b with substituents which extend from the S(1) to the S(3) pocket. Copyright 2009 Elsevier Ltd. All rights reserved.Entities:
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Year: 2009 PMID： 19959359 DOI： 10.1016/j.bmcl.2009.11.052
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823