tetano
Editor, Senior Moderator
Bioorg Med Chem Lett. 2016 Aug 18. pii: S0960-894X(16)30859-9. doi: 10.1016/j.bmcl.2016.08.038. [Epub ahead of print]
[h=1]Discovery of novel 5-hydroxy-4-pyridone-3-carboxy acids as potent inhibitors of influenza Cap-dependent endonuclease.[/h] Miyagawa M[SUP]1[/SUP], Akiyama T[SUP]2[/SUP], Mikamiyama-Iwata M[SUP]2[/SUP], Hattori K[SUP]2[/SUP], Kurihara N[SUP]2[/SUP], Taoda Y[SUP]2[/SUP], Takahashi-Kageyama C[SUP]2[/SUP], Kurose N[SUP]2[/SUP], Mikamiyama H[SUP]2[/SUP], Suzuki N[SUP]2[/SUP], Takaya K[SUP]2[/SUP], Tomita K[SUP]2[/SUP], Matsuo K[SUP]2[/SUP], Morimoto K[SUP]3[/SUP], Yoshida R[SUP]4[/SUP], Shishido T[SUP]4[/SUP], Yoshinaga T[SUP]4[/SUP], Sato A[SUP]4[/SUP], Kawai M[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 IC[SUB]50[/SUB] of 5.12nM.
Copyright ? 2016. Published by Elsevier Ltd.
[h=4]KEYWORDS:[/h] Anti-influenza drug; Cap-dependent endonuclease; Chelator; Pyridone; Virtual modeling
PMID: 27568084 DOI: 10.1016/j.bmcl.2016.08.038
[PubMed - as supplied by publisher]
[h=1]Discovery of novel 5-hydroxy-4-pyridone-3-carboxy acids as potent inhibitors of influenza Cap-dependent endonuclease.[/h] Miyagawa M[SUP]1[/SUP], Akiyama T[SUP]2[/SUP], Mikamiyama-Iwata M[SUP]2[/SUP], Hattori K[SUP]2[/SUP], Kurihara N[SUP]2[/SUP], Taoda Y[SUP]2[/SUP], Takahashi-Kageyama C[SUP]2[/SUP], Kurose N[SUP]2[/SUP], Mikamiyama H[SUP]2[/SUP], Suzuki N[SUP]2[/SUP], Takaya K[SUP]2[/SUP], Tomita K[SUP]2[/SUP], Matsuo K[SUP]2[/SUP], Morimoto K[SUP]3[/SUP], Yoshida R[SUP]4[/SUP], Shishido T[SUP]4[/SUP], Yoshinaga T[SUP]4[/SUP], Sato A[SUP]4[/SUP], Kawai M[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 IC[SUB]50[/SUB] of 5.12nM.
Copyright ? 2016. Published by Elsevier Ltd.
[h=4]KEYWORDS:[/h] Anti-influenza drug; Cap-dependent endonuclease; Chelator; Pyridone; Virtual modeling
PMID: 27568084 DOI: 10.1016/j.bmcl.2016.08.038
[PubMed - as supplied by publisher]