On May 21, 2008, Brak, Katrien; Doyle, Patricia S.; McKerrow, James H.; Ellman, Jonathan A. published an article.COA of Formula: C8H7NOS The title of the article was Identification of a New Class of Nonpeptidic Inhibitors of Cruzain. And the article contained the following:
Cruzain is the major cysteine protease of Trypanosoma cruzi, which is the causative agent of Chagas disease and is a promising target for the development of new chemotherapy. With the goal of developing potent nonpeptidic inhibitors of cruzain, the substrate activity screening (SAS) method was used to screen a library of protease substrates initially designed to target the homologous human protease cathepsin S. Structure-based design was next used to further improve substrate cleavage efficiency by introducing addnl. binding interactions in the S3 pocket of cruzain. The optimized substrates were then converted to inhibitors by the introduction of cysteine protease mechanism-based pharmacophores. Inhibitor 38 was determined to be reversible even though it incorporated the vinyl sulfone pharmacophore that is well documented to give irreversible cruzain inhibition for peptidic inhibitors. The previously unexplored β-chloro vinyl sulfone pharmacophore provided mechanistic insight that led to the development of potent irreversible acyl- and aryl-oxymethyl ketone cruzain inhibitors. For these inhibitors, potency did not solely depend on leaving group pKa, with 2,3,5,6-tetrafluorophenoxymethyl ketone 54 identified as one of the most potent inhibitors with a second-order inactivation constant of 147,000 s-1 M-1. This inhibitor completely eradicated the T. cruzi parasite from mammalian cell cultures and consequently has the potential to lead to new chemotherapeutics for Chagas disease. The experimental process involved the reaction of Benzo[d]thiazol-6-ylmethanol(cas: 19989-66-3).COA of Formula: C8H7NOS
The Article related to nonpeptidic inhibitor cruzain structure chagas disease, Pharmacology: Structure-Activity and other aspects.COA of Formula: C8H7NOS
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica