Elsevier
Tetrahedron
,  volume 175 ,  pages 134519

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

Chao Kan 1, 2
, 
Chongxun Ge 2
, 
Song Liu 2
, 
Song Shi 2
, 
Hu He 2
, 
Weike Su 1
1
 
2
 
Hangzhou SynRx Therapeutics Biomedical Technology Co., Ltd., Hangzhou, Zhejiang, 311121, PR China | 
Publication type: Journal Article
Publication date: 2025-04-01
Elsevier
scimago Q3
wos Q2
SJR: 0.426
CiteScore: 4.1
Impact factor: 2.2
ISSN: 00404020, 14645416
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.
Found 

Are you a researcher?

Create a profile to get free access to personal recommendations for colleagues and new articles.
Metrics
0
Share
Cite this
GOST |
Cite this
GOST Copy
Kan C. et al. Efficient synthesis of imidazo[1,5-a]pyridine sulfonamido derivative as a PARG inhibitor // Tetrahedron. 2025. Vol. 175. p. 134519.
GOST all authors (up to 50) Copy
Kan C., Ge C., Liu S., Shi S., He H., Su W. Efficient synthesis of imidazo[1,5-a]pyridine sulfonamido derivative as a PARG inhibitor // Tetrahedron. 2025. Vol. 175. p. 134519.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.1016/j.tet.2025.134519
UR - https://linkinghub.elsevier.com/retrieve/pii/S0040402025000754
TI - Efficient synthesis of imidazo[1,5-a]pyridine sulfonamido derivative as a PARG inhibitor
T2 - Tetrahedron
AU - Kan, Chao
AU - Ge, Chongxun
AU - Liu, Song
AU - Shi, Song
AU - He, Hu
AU - Su, Weike
PY - 2025
DA - 2025/04/01
PB - Elsevier
SP - 134519
VL - 175
SN - 0040-4020
SN - 1464-5416
ER -
BibTex
Cite this
BibTex (up to 50 authors) Copy
@article{2025_Kan,
author = {Chao Kan and Chongxun Ge and Song Liu and Song Shi and Hu He and Weike Su},
title = {Efficient synthesis of imidazo[1,5-a]pyridine sulfonamido derivative as a PARG inhibitor},
journal = {Tetrahedron},
year = {2025},
volume = {175},
publisher = {Elsevier},
month = {apr},
url = {https://linkinghub.elsevier.com/retrieve/pii/S0040402025000754},
pages = {134519},
doi = {10.1016/j.tet.2025.134519}
}