Open AccessSynthesis and Selective Functionalization of Thiadiazine 1,1-Dioxides with Efficacy in a Model of Huntington’s Disease
Author(s) -
Leila Terrab,
Christopher J. Rosenker,
Lisa Johnstone,
Linh K Ngo,
Li Zhang,
Nathaniel F Ware,
Bettina Miller,
Andrea Z Topacio,
Sara Sannino,
Jeffrey L. Brodsky,
Peter Wipf
Publication year - 2020
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.0c00018
Subject(s) - surface modification , agonist , combinatorial chemistry , chaperone (clinical) , huntington's disease , chemistry , pharmacology , disease , medicine , biochemistry , receptor , pathology
The scope of the acid-mediated 3-component synthesis of thiadiazines was investigated. A selective functionalization of the six-membered heterocyclic core structure was accomplished by sequential alkylations, saponifications, and coupling reactions. Several new analogs of a dihydropyrimidinone Hsp70 chaperone agonist, MAL1-271, showed promising activity in a cell based model of Huntington's disease.