1,4,5,6-Tetrahydrobenzo[2,3]oxepino[4,5-d]pyrimidine derivatives as anti-neuroinflammatory agents: Design, synthesis, and preliminary biological evaluation.

Authors

De-Li Xia, Yu Chen, Guang-Sen Xu, Gui-Ge Hou

Published in

Bioorganic chemistry. Volume 181. Pages 110360. Aug 13, 2026. Epub Aug 13, 2026.

Abstract

Neuroinflammation has been identified as a causative factor of multiple neurological diseases. Microglia cells are the primary immune cells that regulate the neuroinflammation response. Hence, twenty-six 1,4,5,6-tetrahydrobenzo[2,3]oxepino[4,5-d]pyrimidine derivatives (BPMs) as anti-inflammatory molecules were designed and synthesized through two-step structural modification on the basis of the structure of the initial hit DL-1 from an in-house chemical library. The most potent compound 10a, modified with piperidine and benzamidine hydrochloride, was identified as the optimal candidate with strong anti-neuroinflammatory efficacies with no evident cellular cytotoxicity. Treatment with 10a efficiently attenuated LPS-induced neuroinflammation in microglia, as evidenced by reduced levels of inflammatory mediators, including ROS, NO, IL-1β, IL-6, TNF-α, and IL-18. Mechanistic studies demonstrated that 10a inhibits the NF-κB/NLRP3 pathway by suppressing phosphorylation of p65 and IκBα and decreasing NLRP3 protein expression. These results provide a promising strategy and good starting point for the development of a therapeutic candidate for neuroinflammation-related diseases.

PMID:
42603540
Bibliographic data and abstract were imported from PubMed on 16 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.