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Bioorg Med Chem Lett. 2009 Jan 1;19(1):264-74. doi: 10.1016/j.bmcl.2008.10.096. Epub 2008 Oct 25.

Molecular modeling, synthesis, and activity studies of novel biaryl and fused-ring BACE1 inhibitors.

Author information

1
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.

Abstract

A series of transition state analogues of beta-secretases 1 and 2 (BACE1, 2) inhibitors containing fused-ring or biaryl moieties were designed computationally to probe the S2 pocket, synthesized, and tested for BACE1 and BACE2 inhibitory activity. It has been shown that unlike the biaryl analogs, the fused-ring moiety is successfully accommodated in the BACE1 binding site resulting in the ligands with excellent inhibitory activity. Ligand 5b reduced 65% of Abeta40 production in N2a cells stably transfected with Swedish human APP.

PMID:
19013792
PMCID:
PMC2643073
DOI:
10.1016/j.bmcl.2008.10.096
[Indexed for MEDLINE]
Free PMC Article

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