Affordable Access

Publisher Website

Structure-activity relationship refinement and further assessment of indole-3-glyoxylamides as a lead series against prion disease.

Authors
Type
Published Article
Journal
ChemMedChem
1860-7187
Publisher
Wiley Blackwell (John Wiley & Sons)
Publication Date
Volume
6
Issue
1
Pages
115–130
Identifiers
DOI: 10.1002/cmdc.201000383
PMID: 21154498
Source
Medline

Abstract

Structure-activity relationships within the indole-3-glyoxylamide series of antiprion agents have been explored further, resulting in discovery of several new compounds demonstrating excellent activity in a cell line model of prion disease (EC₅₀ <10 nM). After examining a range of substituents at the para-position of the N-phenylglyoxylamide moiety, five-membered heterocycles containing at least two heteroatoms were found to be optimal for the antiprion effect. A number of modifications were made to probe the importance of the glyoxylamide substructure, although none were well tolerated. The most potent compounds did, however, prove largely stable towards microsomal metabolism, and the most active library member cured scrapie-infected cells indefinitely on administration of a single treatment. The present results thereby confirm the indole-3-glyoxylamides as a promising lead series for continuing in vitro and in vivo evaluation against prion disease.

There are no comments yet on this publication. Be the first to share your thoughts.

Statistics

Seen <100 times
0 Comments