Therapeutic Potential of Spirooxindoles as Antiviral Agents

• Published in: ACS infectious diseases Vol. 2; no. 6; pp. 382 - 392
• Main Authors: Ye, Na, Chen, Haiying, Wold, Eric A, Shi, Pei-Yong, Zhou, Jia
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10.06.2016
• Subjects: Animals; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Drug Discovery; Humans; Indoles - chemistry; Indoles - pharmacology; Mice; Oxindoles; Structure-Activity Relationship; Virus Diseases - drug therapy; Virus Diseases - virology; Viruses - drug effects; Viruses - genetics; Viruses - metabolism; influenza virus; spirooxindoles; HIV; RSV; antiviral agents; DENV
• ISSN: 2373-8227; 2373-8227
• DOI: 10.1021/acsinfecdis.6b00041

Antiviral therapeutics with profiles of high potency, low resistance, panserotype, and low toxicity remain challenging, and obtaining such agents continues to be an active area of therapeutic development. Due to their unique three-dimensional structural features, spirooxindoles have been identified as privileged chemotypes for antiviral drug development. Among them, spiro-pyrazolopyridone oxindoles have been recently reported as potent inhibitors of dengue virus NS4B, leading to the discovery of an orally bioavailable preclinical candidate (R)-44 with excellent in vivo efficacy in a dengue viremia mouse model. This review highlights recent advances in the development of biologically active spirooxindoles for their antiviral potential, primarily focusing on the structure–activity relationships (SARs) and modes of action, as well as future directions to achieve more potent analogues toward a viable antiviral therapy.