Optimization of 4-Anilinoquinolines as Dengue Virus Inhibitors

Molecules

卷:26

Pei-Tzu Huang¹  Sirle Saul¹  Shirit Einav¹  Christopher R. M. Asquith² 

[1] Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA;

[2] Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;

关键词: dengue virus (DENV);    4-anilinoquinoline;    flavivirus;    alphavirus;    VEEV;    antivirals;   

DOI  :  10.3390/molecules26237338

来源: DOAJ

【 摘 要 】

Emerging viral infections, including those caused by dengue virus (DENV) and Venezuelan Equine Encephalitis virus (VEEV), pose a significant global health challenge. Here, we report the preparation and screening of a series of 4-anilinoquinoline libraries targeting DENV and VEEV. This effort generated a series of lead compounds, each occupying a distinct chemical space, including 3-((6-bromoquinolin-4-yl)amino)phenol (12), 6-bromo-N-(5-fluoro-1H-indazol-6-yl)quinolin-4-amine (50) and 6-((6-bromoquinolin-4-yl)amino)isoindolin-1-one (52), with EC₅₀ values of 0.63–0.69 µM for DENV infection. These compound libraries demonstrated very limited toxicity with CC₅₀ values greater than 10 µM in almost all cases. Additionally, the lead compounds were screened for activity against VEEV and demonstrated activity in the low single-digit micromolar range, with 50 and 52 demonstrating EC₅₀s of 2.3 µM and 3.6 µM, respectively. The promising results presented here highlight the potential to further refine this series in order to develop a clinical compound against DENV, VEEV, and potentially other emerging viral threats.

【 授权许可】

Unknown