Back to Search Start Over

[1,2,4]Triazolo[1,5-a]pyrimidine derivatives: Structure-activity relationship study leading to highly selective ENPP1 inhibitors.

Authors :
Kawaguchi M
Minami S
Ieda N
Nakagawa H
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2024 Sep 15; Vol. 110, pp. 129820. Date of Electronic Publication: 2024 Jun 06.
Publication Year :
2024

Abstract

The STING (stimulator of interferon genes) pathway is one of the pathways that regulate innate immunity, and the extracellular hydrolytic enzyme ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) has been identified as its dominant negative regulator. Since activation of the innate immune system is a promising strategy for the treatment of various infectious diseases and cancers, ENPP1 inhibitors have attracted great attention as candidate drugs. We have previously identified small-molecule ENPP1 inhibitors having a [1,2,4]triazolo[1,5-a]pyrimidine scaffold by means of chemical screening using a fluorescence probe, TG-mAMP. In this study, we evaluated the structure-activity relationships of the hit and lead compounds in detail, and succeeded in developing compounds that strongly and selectively inhibit ENPP1 not only in vitro, but also in cellular systems.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
110
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
38851358
Full Text :
https://doi.org/10.1016/j.bmcl.2024.129820