Giroud, Maude published the artcileRepurposing a Library of Human Cathepsin L Ligands: Identification of Macrocyclic Lactams as Potent Rhodesain and Trypanosoma brucei Inhibitors, Synthetic Route of 328-90-5, the publication is Journal of Medicinal Chemistry (2018), 61(8), 3350-3369, database is CAplus and MEDLINE.
Rhodesain (RD) is a parasitic, human cathepsin L (hCatL) like cysteine protease produced by Trypanosoma brucei (T. b.) species and a potential drug target for the treatment of human African trypanosomiasis (HAT). A library of hCatL inhibitors was screened, and macrocyclic lactams were identified as potent RD inhibitors (Ki < 10 nM), preventing the cell-growth of Trypanosoma brucei rhodesiense (IC50 < 400 nM). SARs addressing the S2 and S3 pockets of RD were established. Three cocrystal structures with RD revealed a noncovalent binding mode of this ligand class due to oxidation of the catalytic Cys 25 to a sulfenic acid (Cys-SOH) during crystallization The P-glycoprotein efflux ratio was measured and the in vivo brain penetration in rats determined When tested in vivo in acute HAT model, the compounds permitted up to 16.25 (vs. 13.0 for untreated controls) mean days of survival.
Journal of Medicinal Chemistry published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Synthetic Route of 328-90-5.
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