Chinese Journal of Organic Chemistry ›› 2023, Vol. 43 ›› Issue (6): 2143-2155.DOI: 10.6023/cjoc202209033 Previous Articles     Next Articles


孙泽人a, 翟冰新a, 何光超b, 沈慧b, 陈琳雅b, 张杉b, 邹毅a,b, 朱启华a,b,*(), 徐云根a,b,*()   

  1. a 中国药科大学药学院 江苏省药物分子设计与成药性优化重点实验室 南京 211198
    b 中国药科大学药学院 药物化学教研室 南京 211198
  • 收稿日期:2022-09-27 修回日期:2022-11-10 发布日期:2023-01-05
  • 作者简介:
  • 基金资助:

Synthesis and Anti-inflammatory Evaluation of Novel 1,2,3-Triazole Derivatives

Zeren Suna, Bingxin Zhaia, Guangchao Heb, Hui Shenb, Linya Chenb, Shan Zhangb, Yi Zoua,b, Qihua Zhua,b,*(), Yungen Xua,b,*()   

  1. a Jiangsu Key Laboratory of Drug Design and Optimization, School of Pharmacy, China Pharmaceutical University, Nanjing 211198
    b Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 211198
  • Received:2022-09-27 Revised:2022-11-10 Published:2023-01-05
  • Contact: E-mail:;
  • About author:
    These authors contributed equally to this work
  • Supported by:
    National Natural Science Foundation of China(81872750)

As the role of indoleamine 2,3-dioxygenase 2 (IDO2) in inflammation, especially in rheumatoid arthritis (RA), is gradually being explained, IDO2 has become a potential target for the treatment of RA. No small molecule inhibitor of IDO2 with strong activity and high selectivity has been reported yet. With the help of computer-aided drug design, twenty-four 1,2,3-triazole derivatives were designed and synthesized by using epacadostat as a lead compound. The results of biological activity show that all target compounds display the inhibitory effects on IDO1 and IDO2 enzymes. Among them, the inhibition rates of (Z)-N-((1-(2-((4-(N-(3-bromo-4-fluorophenyl)-N'-hydroxyformamidine)-1,2,5-oxadiazo-3-yl)amino)ethyl)-1H-1,2,3- triazol-4-yl)methyl) (I-11) on indoleamine 2,3-dioxygenase 1 (IDO1) and IDO2 enzymes were 76% and 49% at 100 nmol/L concentration, respectively, which are better than those of epacadostat (62% and 25%). The anti-inflammatory activity study showed that compound I-11 could significantly inhibit the secretion of inflammatory factor TNF-α at the cellular level. Compound I-11 also showed good in vivo anti-inflammatory activity in mouse ear swelling model, and the inhibition rate was 56.81% at the dose of 100 mg/kg (Ig) which was better than that of naproxen (45.29%, 150 mg/kg, Ig).

Key words: indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), 1,2,3-triazole, anti-inflammatory activity