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Thiophene substituted acylguanidines as BACE1 inhibitors

Authors :
Jonathan A. Bard
Michael S. Malamas
E.S. Manas
Guixan Jin
Rebecca Cowling
Albert J. Robichaud
William Ronald Solvibile
Yun Hu
Jim Turner
Erik Wagner
William Floyd Fobare
Rajiv Chopra
Source :
Bioorganic & Medicinal Chemistry Letters. 17:5353-5356
Publication Year :
2007
Publisher :
Elsevier BV, 2007.

Abstract

A series of thiophene-substituted acylguanidines were designed from a pyrrole substituted acylguanidine HTS lead. This template allowed a greater flexibility, through differential Suzuki couplings, to explore the binding site of BACE1 and to enhance the inhibitory potencies. This exploration provided a 25-fold enhancement in potency to yield compound 10a, which was 150 nM in a BACE1 FRET assay.

Details

ISSN :
0960894X
Volume :
17
Database :
OpenAIRE
Journal :
Bioorganic & Medicinal Chemistry Letters
Accession number :
edsair.doi.dedup.....bc4b3dd8fc11b23029f7bcb83b6b9caa