1072919-42-6Relevant articles and documents
Structure–activity relationship studies on quinoxalin-2(1H-one derivatives containing thiazol-2-amine against hepatitis C virus leading to the discovery of BH6870
Zhong, Qi-Fei,Liu, Rui,Liu, Gang
, p. 829 - 853 (2015)
Abstract: Chronic hepatitis C virus infection represents a serious global public health problem, typically resulting in fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Based on our previous discovery of lead compound 2 (Liu et al. J Med Chem 54:5747–5768, 2011), 35 new quinoxalinone derivatives were explored in this study. Outline of the structure–activity relationships (SARs) revealed that compound BH6870 (36) showed high anti-HCV potency (EC50 = 0.21μM) and a good cell safety index (SI =47.19). SARs analysis indicated that quinoxalin-2(1H-one containing a 4-aryl-substituted thiazol-2-amine moiety was optimal for antiviral activity. Introducing a hydrogen-bond acceptor (such as ester or amide group) at the C-3 position of quinoxalin-2(1H-one was beneficial for the antiviral potency, and especially, N,N-disubstituted amide was far superior to N-monosubstituted amide. Incorporation of more than one halogen (fluorine or chlorine atom) or a strong electron-withdrawing group on the benzene ring of the thiazole-phenyl moiety might reduce electron atmosphere density further and resulted in a dramatical loss of activity. The NH-group of the lactam moiety was clearly required for anti-HCV activity. Graphical Abstract: Design and synthesis of quinoxalin-2(1H-one derivatives as new non-nucleoside small-molecule HCV inhibitors. BH6870 (36), showing higher antiviral potency and a good cell safety index, was identified. [Figure not available: see fulltext.]
