On June 18, 2009, Ellman, Jonathan A.; Brak, Katrien published a patent.Related Products of 19989-66-3 The title of the patent was Triazole derivatives and aminocoumarin derivatives as nonpeptidic inhibitors of cruzain and their preparation and use in the treatment of Chagas disease. And the patent contained the following:
Cruzain is the major cysteine protease of T. cruzi, which is the causative agent of Chagas’ disease and is a promising target for the development of chemotherapy. With the goal of developing potent nonpeptidic inhibitors of cruzain, of formula I, the substrate activity screening 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. Substrates of formula I wherein R1 is H, OH and derivatives, NH2 and derivatives, SH and derivatives, SOH and derivatives, SO2H and derivatives, SO2NH2 and derivatives, NO2, halo, CN, (un)substituted (hetero)alkyl, etc.; are claimed. The optimized substrates were then converted to inhibitors by the introduction of cysteine protease mechanism-based pharmacophores. Inhibitors II and III were prepared by multistep procedures (procedures given). Inhibitor II 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 pTa, with 2,3,5,6-tetrafluorophenoxy Me ketone III identified as one of the most potent inhibitors with a second order inactivation constant of 147,000 s-1M-1. This inhibitor completely eradicated the T. cruzi parasite from mammalian cell cultures and consequently has the potential to lead to new chemo therapeutics for Chagas’ disease. The experimental process involved the reaction of Benzo[d]thiazol-6-ylmethanol(cas: 19989-66-3).Related Products of 19989-66-3
The Article related to triazole derivative preparation nonpeptidic cruzain inhibitor treatment chagas disease, aminocoumarin derivative preparation nonpeptidic cruzain inhibitor treatment chagas disease and other aspects.Related Products of 19989-66-3
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica