Novel Competitive, Nonpeptidic, SARS-CoV-2 Mpro Inhibitors with Improved Solubility
ACS Medicinal Chemistry Letters, cilt.17, sa.5, ss.1132-1137, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Kısa Makale
- Cilt numarası: 17 Sayı: 5
- Basım Tarihi: 2026
- Doi Numarası: 10.1021/acsmedchemlett.6c00041
- Dergi Adı: ACS Medicinal Chemistry Letters
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE
- Sayfa Sayıları: ss.1132-1137
- Anahtar Kelimeler: COVID-19, FEP+, main protease, SARS-CoV-2
- Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Evet
Özet
In continuation of our previous work wherein we described novel, nonpeptidic competitive inhibitors of the SARS-CoV-2 main protease, we here describe our efforts to improve upon these compounds by improving water solubility and metabolic stability. As predicted by FEP+ solubility studies, disrupting the coplanar arrangement of the aromatic rings led to significantly improved compound aqueous solubility, unfortunately with an unacceptable loss in potency. Attempts to improve compound metabolic stability by avoiding aromatic moieties occupying the S4 pocket, while retaining compound potency by modification of the pyridyl ring occupying the S1 pocket, were also investigated.