Novel influenza polymerase PB2 inhibitors for the treatment of influenza A infection

Bioorg Med Chem Lett. 2019 Oct 15;29(20):126639. doi: 10.1016/j.bmcl.2019.126639.

Hongwang Zhang ¹, Longhu Zhou ¹, Sarah Amichai ¹, Keivan Zandi ¹, Bryan Cox ¹, Raymond Schinazi ¹, Franck Amblard ²

Affiliations

1 Center for AIDS Research, Global Virus Network, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
2 Center for AIDS Research, Global Virus Network, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: [email protected].

PMID: 31493987 DOI: 10.1016/j.bmcl.2019.126639

Abstract

Exploration of the chemical space of known influenza polymerase PB2 inhibitor Pimodivir, was performed by our group. We synthesized and identified compounds 16a and 16b, two novel thienopyrimidine derivatives displaying anti-influenza A activity in the single digit nanomolar range in Cell Culture. Binding of these unique compounds in the influenza polymerase PB2 pocket was also determined using molecular modeling.

Keywords

Antiviral; Flu; Influenza A; Virus.

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