9-Sulfonyl-9(H)-Purine Derivatives Inhibit HCV Replication Via their Degradation Species
| العنوان: | 9-Sulfonyl-9(H)-Purine Derivatives Inhibit HCV Replication Via their Degradation Species |
|---|---|
| المؤلفون: | Rong Hu, Wan-Li Wang, Ning-Yu Wang, Kun-Jie Xiao |
| المصدر: | Pharmaceutical Chemistry Journal. 55:36-45 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Pharmacology, chemistry.chemical_classification, Sulfonyl, Purine, 010405 organic chemistry, Chemistry, Hepatitis C virus, Cell, medicine.disease_cause, 01 natural sciences, Small molecule, 0104 chemical sciences, Sulfonamide, 010404 medicinal & biomolecular chemistry, chemistry.chemical_compound, medicine.anatomical_structure, Biochemistry, Mechanism of action, Drug Discovery, medicine, medicine.symptom, Purine metabolism |
| الوصف: | Cell-based screening of a privileged small molecule library led to the discovery of 9-sulfonyl-9(H)-purine as new scaffold for hepatitis C virus (HCV) inhibitors. Structure–activity relationship study with respect to the 2-, 6- and 9-positions in the purine core resulted in the identification of several active compounds with moderate potency against the HCV genotype 1b. Subsequent stability studies demonstrated that HCV inhibitors of this type were unstable in Dulbecco’s modified eagle medium (DMEM) and plasma, as well as glutathione-containing water, and their instability was closely related to their HCV inhibitory activity. A preliminary study of the mechanism of action showed that the sulfonamide bond at the 9-position of purine would be the primary degradation site and the resulting sulfonylation degradation species would mediate the anti-HCV activity of 9-sulfonyl-9(H)-purines. Results of this study demonstrated that 9-sulfonyl-9(H)-purine is an unstable scaffold for HCV inhibitors and further detailed analysis of the degradation species is needed to determine the main active components and direct target for this type of molecules. |
| تدمد: | 1573-9031 0091-150X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::5739b3ac0a532b3caf7d3a093e0087bf https://doi.org/10.1007/s11094-021-02369-1 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........5739b3ac0a532b3caf7d3a093e0087bf |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15739031 0091150X |
|---|