22DR

Crystal structure of SARS-CoV-2 3CL protease in complex with compound 7c

これはPDB形式変換不可エントリーです。

22DR の概要

• エントリーDOI: 10.2210/pdb22dr/pdb
• 分子名称: 3C-like proteinase, 7-[(3~{R})-3-fluoranylpyrrolidin-1-yl]-5-methoxy-3-[(1-methyl-1,2,4-triazol-3-yl)methyl]-1-[[3,4,5-tris(fluoranyl)phenyl]methyl]pyrido[4,3-d]pyrimidine-2,4-dione, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69102.39

構造登録者

Taoda, Y.,Hirai, K.,Sugiyama, S.,Tanaka, S.,Tomida, Y.,Akiyama, T.,Nakahara, K.,Unoh, Y.,Tachibana, Y.,Uehara, S.,Sako, Y.,Yamamoto, S.,Kawashima, S.,Nobori, H.,Kato, T. (登録日: 2026-01-07, 公開日: 2026-03-25)

主引用文献

Taoda, Y.,Hirai, K.,Sugiyama, S.,Tanaka, S.,Tomida, Y.,Akiyama, T.,Nakahara, K.,Unoh, Y.,Tachibana, Y.,Uehara, S.,Sako, Y.,Yamamoto, S.,Kawashima, S.,Nobori, H.,Kato, T.
Optimization of pyridopyrimidinedione derivatives as non-covalent SARS-CoV-2 3CL protease inhibitors.
Bioorg.Med.Chem.Lett., 136:130619-130619, 2026

PubMed Abstract: COVID-19, an infectious disease caused by SARS-CoV-2, first identified in Wuhan, China, in 2019 and rapidly spread around the world. In response to this worldwide crisis, the research and development of antiviral drugs advanced together with vaccines, and several medications are currently being used for treatment. This study aimed to explore the structure-activity relationships (SAR) of non-covalent inhibitors of the SARS-CoV-2 3CL protease (3CL) and to develop more potent inhibitors starting from ensitrelvir, a potent non-peptide small-molecule 3CL inhibitor discovered by Shionogi & Co., Ltd. Although a previously reported dihydrofuran-ring-fused tricyclic compound 1 exhibited high antiviral activity, there were issues with its metabolic stability and solubility. Therefore, we focused on compound 2, which has a pyridopyrimidinedione scaffold, and tried to optimize its structure. Here we report compounds that have improved antiviral activity while maintaining enzyme inhibitory activity and enhanced solubility. In particular, compound 18f demonstrated a balance of potent activity, high solubility, and excellent metabolic stability. Its favorable pharmacokinetics were also confirmed in rat PK tests, suggesting that this compound offers promise as a new therapeutic agent.

PubMed: 41819156
DOI: 10.1016/j.bmcl.2026.130619

実験手法

X-RAY DIFFRACTION (1.9 Å)