Publication
Title
2-amino-3,4-dihydroquinazolines as inhibitors of BACE-1 (-site APP cleaving enzyme) : use of structure based design to convert a micromolar hit into a nanomolar lead
Author
Abstract
A new aspartic protease inhibitory chemotype bearing a 2-amino-3,4-dihydroquinazoline ring was identified by high-throughput screening for the inhibition of BACE-1. X-ray crystallography revealed that the exocyclic amino group participated in a hydrogen bonding array with the two catalytic aspartic acids of BACE-1 (Asp(32), Asp(228)). BACE-1 inhibitory potency was increased (0.9 mu M to 11 nM K-i) by substitution into the unoccupied S-1 ' pocket.
Language
English
Source (journal)
Journal of medicinal chemistry. - Washington, D.C., 1963, currens
Publication
Washington, D.C. : 2007
ISSN
0022-2623
Volume/pages
50:18(2007), p. 4261-4264
ISI
000249150700001
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 11.12.2013
Last edited 02.11.2017