Cyclic Hydroxyamidines as Amide Isosteres: Discovery of Oxadiazolines and Oxadiazines as Potent and Highly Efficacious γ-Secretase Modulators in Vivo

Autor:	Xianhai Huang, Eric M. Parker, Xiaoxiang Liu, Gioconda V. Gallo, Thomas A. Bara, Lili Zhang, Lixin Song, Ruo Xu, Hongmei Li, William J. Greenlee, Troy Mccracken, Xiaohong Zhu, Theodros Asberom, Nicholas Jones, Monica L. Vicarel, Mihir B. Mandal, Julie Lee, Zhaoning Zhu, Qi Zhang, John W. Clader, Dmitri A. Pissarnitski, Mary Cohen-Williams, Lynn A. Hyde, Johannes H. Voigt, Irina Kazakevich, James Durkin, Jun Qin, Michael Czarniecki, Hubert B. Josien, Amin A. Nomeir, Duane A. Burnett, Chad E. Bennett, Zhong-Yue Sun, Robert Mazzola, Giuseppe Terracina, David Cole, Zhiqiang Zhao, Inhou Chu, Malcolm Maccoss, Anandan Palani
Rok vydání:	2011
Předmět:	Male Oxadiazoles Amyloid beta-Peptides Chemistry Amidines Brain Stereoisomerism Combinatorial chemistry Peptide Fragments Rats Macaca fascicularis Structure-Activity Relationship chemistry.chemical_compound Dogs HEK293 Cells In vivo Amide Oxazines Drug Discovery Animals Humans Molecular Medicine γ secretase Amyloid Precursor Protein Secretases Structural motif
Zdroj:	Journal of Medicinal Chemistry. 55:489-502
ISSN:	1520-4804 0022-2623
Popis:	Cyclic hydroxyamidines were designed and validated as isosteric replacements of the amide functionality. Compounds with these structural motifs were found to be metabolically stable and to possess highly desirable pharmacokinetic profiles. These designs were applied in the identification of γ-secretase modulators leading to highly efficacious agents for reduction of central nervous system Aβ(42) in various animal models.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2c0f39de1cb62f536e58373ca41057aa https://doi.org/10.1021/jm201407j Zobrazit plný text záznamu