Efficient synthesis of imidazo[1,5-a]pyridine sulfonamido derivative as a PARG inhibitor

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron Pub Date : 2025-01-31 DOI:10.1016/j.tet.2025.134519

Chao Kan , Chongxun Ge , Song Liu , Song Shi , Hu He , Weike Su

引用次数: 0

Abstract

The potential of PARG, the most active dePARylation enzyme, as a therapeutic target lies in its synthetic lethal relationship with other DNA repair genes. The development of PARG inhibitors represents a significant advancement in precision medicine. Currently, no PARG-targeted drugs are available commercially, with the most advanced candidates still in the Phase I clinical trial stage. Herein, we described the route screening and process development for SYN419, a potent PARG inhibitor. The critical imidazo[1,5-a]pyridine core 18 was successfully scaled up to kilogram production. Utilizing 13-step parallel reactions, we obtained the target compound SYN419 and scaled up to tens of grams, quickly fulfilling the material requirement for pre-toxicological study.

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来源期刊

Tetrahedron 化学-有机化学

CiteScore

3.90

自引率

4.80%

发文量

439

审稿时长

34 days

期刊介绍： Tetrahedron publishes full accounts of research having outstanding significance in the broad field of organic chemistry and its related disciplines, such as organic materials and bio-organic chemistry. Regular papers in Tetrahedron are expected to represent detailed accounts of an original study having substantially greater scope and details than that found in a communication, as published in Tetrahedron Letters. Tetrahedron also publishes thematic collections of papers as special issues and ''Reports'', commissioned in-depth reviews providing a comprehensive overview of a research area.