Swarbrick, Crystall; Zogali, Vasiliki; Chan, Kitti Wing Ki; Kiousis, Dimitrios; Gwee, Chin Piaw; Wang, Sai; Lescar, Julien; Luo, Dahai; von Itzstein, Mark; Matsoukas, Minos-Timotheos; Panagiotakopoulos, George; Vasudevan, Subhash G.; Rassias, Gerasimos published their research in European Journal of Medicinal Chemistry in 2021. The article was titled 《Amidoxime prodrugs convert to potent cell-active multimodal inhibitors of the dengue virus protease》.Reference of 3,6-Dibromo-9H-carbazole The article contains the following contents:
The flavivirus genus of the Flaviviridae family comprises Dengue, Zika and West-Nile viruses which constitute unmet medical needs as neither appropriate antivirals nor safe vaccines are available. The dengue NS2BNS3 protease is one of the most promising validated targets for developing a dengue treatment however reported protease inhibitors suffer from toxicity and cellular inefficacy. Here we report SAR on our previously reported Zika-active carbazole scaffold, culminating in prodrug compound SP-471P (EC50 1.10μM, CC50 > 100μM) that generates SP-471 (I → II); one of the most potent, non-cytotoxic and cell-active protease inhibitors described in the dengue literature. In cell-based assays, SP-471P leads to inhibition of viral RNA replication and complete abolishment of infective viral particle production even when administered 6 h post-infection. Mechanistically, SP-471 appears to inhibit both normal intermol. protease processes and intramol. cleavage events at the NS2BNS3 junction, as well as at NS3 internal sites, all critical for virus replication. These render SP-471 a unique to date multimodal inhibitor of the dengue protease. The results came from multiple reactions, including the reaction of 3,6-Dibromo-9H-carbazole(cas: 6825-20-3Reference of 3,6-Dibromo-9H-carbazole)
3,6-Dibromo-9H-carbazole(cas: 6825-20-3) is used as a reagent in the synthesis of P7C3-A20 which is a potent neuroprotective agent. And it has been used in the preparation of N-(2-hydroxyethyl)-3,6-dibromocarbazole.Reference of 3,6-Dibromo-9H-carbazole
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary