| Literature DB >> 27568084 |
Masayoshi Miyagawa1, Toshiyuki Akiyama2, Minako Mikamiyama-Iwata2, Kazunari Hattori2, Naoko Kurihara2, Yoshiyuki Taoda2, Chika Takahashi-Kageyama2, Noriyuki Kurose2, Hidenori Mikamiyama2, Naoyuki Suzuki2, Kenji Takaya2, Kenji Tomita2, Kenji Matsuo2, Kenji Morimoto3, Ryu Yoshida4, Takao Shishido4, Tomokazu Yoshinaga4, Akihiko Sato4, Makoto Kawai2.
Abstract
We report the discovery of a novel series of influenza Cap-dependent EndoNuclease (CEN) inhibitors based on the 4-pyridone-carboxylic acid (PYXA) scaffold, which were found from our chelate library. Our SAR research revealed the lipophilic domain to be the key to CEN inhibition. In particular, the position between the chelate and the lipophilic domain in the derivatives was essential for enhancing the potency. Our study, based on virtual modeling, led to the identification of 2y as a potent CEN inhibitor with an IC50 of 5.12nM.Entities:
Keywords: Anti-influenza drug; Cap-dependent endonuclease; Chelator; Pyridone; Virtual modeling
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Year: 2016 PMID： 27568084 DOI： 10.1016/j.bmcl.2016.08.038
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823