Identification of N, C-capped di- and tripeptides as selective immunoproteasome inhibitors was written by Nan, Guanglei;Huang, Lei;Li, Yunxuan;Yang, Yajun;Yang, Ying;Li, Ke;Lai, Fangfang;Chen, Xiaoguang;Xiao, Zhiyan. And the article was included in European Journal of Medicinal Chemistry in 2022.Synthetic Route of C7H4N2O2S The following contents are mentioned in the article:
A series of N, C-capped di- and tripeptides were designed as selective immunoproteasome inhibitors based on the known inhibitor 4-CA. Forty-eight new compounds were synthesized and evaluated, and the structure-activity relationship (SAR) of this compound class as β5i selective inhibitors were explored. Most of these compounds showed significant inhibition against the β5i subunit of the immunoproteasome and the most potent β5i inhibitor (15) showed an IC50 of 0.94 nM. A selective β5i inhibitor (54) with over 500-fold β5i/β5c selectivity was identified. Three of the inhibitors were found to selectively inhibit β5i and β5c, and showed no noticeable inhibition against the other four subunits. Six inhibitors with significant inhibitory activity against the HCT-116 cells were recognized, and the most active inhibitors, 14 and 50, showed IC50 values of 0.46 μM and 0.16 μM, resp. Some selective β5i inhibitors exhibited significant inhibitory effects on the release of the cytokines TNF-α and IL-6. The results not only afford effective chem. tools to elucidate the relationships between subunit selectivity and pharmacol. profiles, but also offer useful clues for further optimization and development of selective immunoproteasome inhibitors. This study involved multiple reactions and reactants, such as 2-Cyano-3-(thiazol-2-yl)acrylic acid (cas: 1567534-28-4Synthetic Route of C7H4N2O2S).
2-Cyano-3-(thiazol-2-yl)acrylic acid (cas: 1567534-28-4) belongs to thiazole derivatives. Thiazoles frequently appear in peptide studies. Thiazoles can also be used as protected formyl groups, which can be released in later stages of complex natural product synthesis. The pyridine-type nitrogen in the thiazole ring deactivates the ring for electrophilic substitution reactions, which is further reduced in acid due to protonation of the thiazole ring.Synthetic Route of C7H4N2O2S
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica