ensitrelvir   Click here for help

GtoPdb Ligand ID: 11871

Synonyms: compound 3 [PMID: 35352927] | compound I-0006 [WO2022138987] [2] | S-217622 | S217622 | Xocova®
Approved drug PDB Ligand
ensitrelvir is an approved drug (Japan 2022)
Compound class: Synthetic organic
Comment: Ensitrelvir is a newly proposed INN for an antiviral that was revealed in January 2022, in the COVID special section of Proposed List 126. It was therefore assumed to target SARS-CoV-2, and to be a potential drug for the treatment of patients with SARS-CoV-2 infection (COVID-19). We were able to match this chemical structure to the Shiongi lead compound S-217622, following their preprint disclosure. The Shiongi article was subsequently published in J Med Chem in March 2022 [3]. S-217622 is described as a non-covalent oral Mpro inhibitor, with pharmacokinetics that support once-daily dosing. It was formulated as a 1:1 fumaric acid complex. Molecular dynamics simulation has been used to estimate ensitrelvir's effectiveness against 6 common SARS-CoV-2 variants (Alpha AP.1, Beta B.1.351, Gamma P.1.13, Delta AY.116, Omicron BA.1/2/3/4/5 and Lambda C.37) [4].
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 99.96
Molecular weight 531.11
XLogP 4.25
No. Lipinski's rules broken 0
Click here for help
Canonical SMILES Cn1cnc(n1)Cn1c(=O)[nH]/c(=N\c2cc3cn(nc3cc2Cl)C)/n(c1=O)Cc1cc(F)c(cc1F)F
Isomeric SMILES Clc1c(cc2cn(nc2c1)C)/N=c/1\[nH]c(=O)n(c(=O)n1Cc1c(cc(c(c1)F)F)F)Cc1nn(cn1)C
InChI InChI=1S/C22H17ClF3N9O2/c1-32-7-12-4-18(13(23)5-17(12)30-32)28-20-29-21(36)35(9-19-27-10-33(2)31-19)22(37)34(20)8-11-3-15(25)16(26)6-14(11)24/h3-7,10H,8-9H2,1-2H3,(H,28,29,36)
1. Mukae H, Yotsuyanagi H, Ohmagari N, Doi Y, Imamura T, Sonoyama T, Fukuhara T, Ichihashi G, Sanaki T, Baba K et al.. (2022)
A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-Like Protease Inhibitor, in Japanese Patients with Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part.
Antimicrob Agents Chemother, 66 (10): e0069722. [PMID:36098519]
2. Tachibana Y, Uehara S, Unoh Y, Nakahara K, Taoda Y, Kasamatsu K, Yamatsu Y, Ando S, Iimuro A, Suto T et al.. (2022)
Triazine derivative having virus propagation inhibitory effect, and pharmaceutical composition containing same.
Patent number: WO202213898. Assignee: Shiongi & Co. Ltd., National University Corporation Hokkaido University, Japan. Priority date: 17/02/2022. Publication date: 30/06/2022.
3. Unoh Y, Uehara S, Nakahara K, Nobori H, Yamatsu Y, Yamamoto S, Maruyama Y, Taoda Y, Kasamatsu K, Suto T et al.. (2022)
Discovery of S-217622, a Noncovalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19.
J Med Chem, 65 (9): 6499-6512. [PMID:35352927]
4. Xiong D, Zhao X, Luo S, Zhang JZH, Duan L. (2022)
Molecular Mechanism of the Non-Covalent Orally Targeted SARS-CoV-2 Mpro Inhibitor S-217622 and Computational Assessment of Its Effectiveness against Mainstream Variants.
J Phys Chem Lett, 13 (38): 8893-8901. [PMID:36126063]