1370248-34-2Relevant academic research and scientific papers
Synthesis and SAR Study of Carbamoyl Pyridone Bicycle Derivatives as Potent Inhibitors of Influenza Cap-dependent Endonuclease
Miyagawa, Masayoshi,Akiyama, Toshiyuki,Taoda, Yoshiyuki,Takaya, Kenji,Takahashi-Kageyama, Chika,Tomita, Kenji,Yasuo, Kazuya,Hattori, Kazunari,Shano, Shinya,Yoshida, Ryu,Shishido, Takao,Yoshinaga, Tomokazu,Sato, Akihiko,Kawai, Makoto
, p. 8101 - 8114 (2019)
The medicinal chemistry and structure-activity relationships (SAR) for a novel series of carbamoyl pyridone bicycle (CAB) compounds as influenza Cap-dependent endonuclease (CEN) inhibitors are disclosed. Substituent effects were evaluated at the C (N)-1, N-3, and C-7 positions of the CAB ring system using a docking study. Submicromolar EC50 values were achieved in the cellular assay with C-7-unsubstituted CAB which possessed a benzhydryl group on either the C-1 or the N-1 position. An N-3 substituent was found to be critical for the plasma protein binding effect in vitro, and the CAB-N analogue 2v exhibited reasonable total clearance (CLtot). More importantly, compound 2v displayed significant efficacy in a mouse model infected with influenza viruses.
SUBSTITUTED POLYCYCLIC CARBAMOYL PYRIDONE DERIVATIVE PRODRUG
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Paragraph 1007; 1011; 1012; 1013, (2013/08/14)
The present invention provides a compound having antiviral effects, particularly having growth inhibitory activity on influenza viruses, a preferred example of the compound being a substituted 3-hydroxy-4-pyridone derivative prodrug having cap-dependent endonuclease inhibitory activity.
