Design, Synthesis and Preliminary Biological Evaluation of Chromone-Based PDE10A Inhibitors

doi:10.7503/cjcu20260158

Chem. J. Chinese Universities

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Design, Synthesis and Preliminary Biological Evaluation of Chromone-Based PDE10A Inhibitors

WU Weijun¹，HE Jiajing¹，WU Junpeng¹，LAN Kunyan¹，WU Zheng^1,2

1. College of Pharmacy, Guangxi Medical University
2. Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Guangxi Medical University

Received:2026-04-17 Revised:2026-07-06 Online First:2026-07-12 Published:2026-07-12
Supported by:
Supported by the National Natural Foundation of China (No.82260671)

1. ESM to 20260158.pdf(1597KB)

Abstract

Abstract: Based on the comprehensive analysis of the PDE10A protein structure and the interaction patterns of existing inhibitors, using the hybrid principle, ten new PDE10A inhibitors that have not been reported in the literature were designed and synthesized. The activity test results showed that except for compounds A4 and A5, the remaining compounds all exhibited varying degrees of inhibitory activity (IC50= 38.83~98.83 nmol/L). The most active compounds A1, A2, and A9 were selected for molecular docking, and it was found that they could all insert into the hydrophobic layer formed by PHE729 and ILE692/PHE696 in the PDE10A protein, exerting inhibitory effects through π-π stacking and hydrogen bonds. The ADMET prediction results indicated that these three compounds had good intestinal absorption properties, low blood-brain barrier permeability, and low toxicity, and had the potential to be further developed as lead compounds.

Key words: Chromone; PDE10A inhibitor, Synthesis, Molecular docking, ADMET

CLC Number:

O262

TrendMD:

WU Weijun, HE Jiajing, WU Junpeng, LAN Kunyan, WU Zheng. Design, Synthesis and Preliminary Biological Evaluation of Chromone-Based PDE10A Inhibitors[J]. Chem. J. Chinese Universities, doi: 10.7503/cjcu20260158.

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Design, Synthesis and Preliminary Biological Evaluation of Chromone-Based PDE10A Inhibitors

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