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Cover Picture: Design and Synthesis of 2,3,5‐Substituted Imidazolidin‐4‐one Inhibitors of BACE‐1 (ChemMedChem 7/2007)
Author(s) -
Barrow James C.,
Rittle Kenneth E.,
Ngo Phung L.,
Selnick Harold G.,
Graham Samuel L.,
Pitzenberger Steven M.,
McGaughey Georgia B.,
Colussi Dennis,
Lai MingTain,
Huang Qian,
Tugusheva Katherine,
Espeseth Amy S.,
Simon Adam J.,
Munshi Sanjeev K.,
Vacca Joseph P.
Publication year - 2007
Publication title -
chemmedchem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200790022
Subject(s) - chemistry , hydrogen bond , ring (chemistry) , cover (algebra) , combinatorial chemistry , active site , stereochemistry , catalysis , molecule , biochemistry , organic chemistry , mechanical engineering , engineering
The cover picture shows a close‐up view of a modified hydroxyethylamine aspartyl protease inhibitor bound in the BACE‐1 active site. The imidazolidinone ring serves as a rigid scaffold for orienting substituents into the S1' and S2' sites of the enzyme while making hydrogen bond contacts to the catalytic aspartate groups (highlighted in red) and the flap (colored in blue). Based on this X‐ray crystal structure, additional analogues were designed to exploit the imidazolidinone heterocycle as a template for potent BACE‐1 inhibitors. For details, see the Communication by J. Barrow et al. on p. 995 ff.