2QMG

Structure of BACE Bound to SCH745966

Summary for 2QMG

• Entry DOI: 10.2210/pdb2qmg/pdb
• Related: 2qk5 2qkj 2qmd 2qmf 2qp8
• Descriptor: Beta-secretase 1, N-{(1S,2R)-1-(3,5-DIFLUOROBENZYL)-2-HYDROXY-2-[(2R,4R)-4-PHENOXYPYRROLIDIN-2-YL]ETHYL}-3-{[(2R)-2-(METHOXYMETHYL)PYRROLIDIN-1-YL]CARBONYL}-5-METHYLBENZAMIDE, D(-)-TARTARIC ACID, ... (4 entities in total)
• Functional Keywords: bace1, protease, alternative splicing, aspartyl protease, glycoprotein, hydrolase, membrane, transmembrane, zymogen
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P56817
• Total number of polymer chains: 2
• Total formula weight: 89394.67

Authors

Strickland, C.O.,Iserloh, U. (deposition date: 2007-07-16, release date: 2008-03-18, Last modification date: 2024-10-30)

Primary citation

Iserloh, U.,Pan, J.,Stamford, A.W.,Kennedy, M.E.,Zhang, Q.,Zhang, L.,Parker, E.M.,McHugh, N.A.,Favreau, L.,Strickland, C.,Voigt, J.
Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor.
Bioorg.Med.Chem.Lett., 18:418-422, 2008

PubMed Abstract: Based on a lead compound identified from the patent literature, we developed patentably novel BACE-1 inhibitors by introducing a cyclic amine scaffold as embodied by 1a and 1b. Extensive SAR studies assessed a variety of isophthalamide replacements including substituted pyrrolidinones and ultimately led to the identification of 11. Due to its favorable overall profile, 11 has been extensively profiled in various in vivo settings.

PubMed: 17980584
DOI: 10.1016/j.bmcl.2007.10.053

Experimental method

X-RAY DIFFRACTION (1.89 Å)