Piperazine sulfonamide BACE1 inhibitors: design, synthesis, and in vivo characterization

Autor:	Reshma Kuvelkar, Peter Orth, Nansie A. McHugh, Xia Chen, Corey Strickland, Carolyn Carrol, Babu Suresh D, Eric M. Parker, Jared N. Cumming, Dawit Tadesse, Guoqing Li, Johannes H. Voigt, Le Thuy X H, Lynne E. Ozgur, Matthew E. Kennedy, Kurt W. Saionz, William J. Greenlee, Tao Guo, Ying Huang, Andrew Stamford, Lili Zhang, Qi Zhang, Leonard Favreau
Rok vydání:	2010
Předmět:	Models Molecular Molecular model Stereochemistry Peptidomimetic Clinical Biochemistry Pharmaceutical Science Mice Transgenic Crystallography X-Ray Biochemistry Piperazines chemistry.chemical_compound Mice Structure-Activity Relationship In vivo Alzheimer Disease Drug Discovery Hydrolase Animals Aspartic Acid Endopeptidases Protease Inhibitors Molecular Biology Piperazine chemistry.chemical_classification Sulfonamides Amyloid beta-Peptides Binding Sites Chemistry Organic Chemistry Combinatorial chemistry Peptide Fragments Sulfonamide Enzyme Design synthesis Drug Design Molecular Medicine Amyloid Precursor Protein Secretases
Zdroj:	Bioorganicmedicinal chemistry letters. 20(9)
ISSN:	1464-3405
Popis:	With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2{prime} sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral A{beta}{sub 40} in transgenic mice with a single subcutaneous dose.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bce47ecc08f0df426003b46dd9c6b44f https://pubmed.ncbi.nlm.nih.gov/20347593 Zobrazit plný text záznamu Full Text from ScienceDirect