Zhang, Chun-Hui published the artcileOptimization of triarylpyridinone inhibitors of the main protease of SARS-CoV-2 to low-nanomolar antiviral potency, SDS of cas: 1256345-74-0, the publication is ACS Medicinal Chemistry Letters (2021), 12(8), 1325-1332, database is CAplus and MEDLINE.
Non-covalent inhibitors of the main protease (Mpro) of SARS-CoV-2 having a pyridinone core were previously reported with IC50 values as low as 0.018μM for inhibition of enzymic activity and EC50 values as low as 0.8μM for inhibition of viral replication in Vero E6 cells. The series has now been further advanced by consideration of placement of substituted five-membered-ring heterocycles in the S4 pocket of Mpro and N-methylation of a uracil ring. Free energy perturbation calculations provided guidance on the choice of the heterocycles, and protein crystallog. confirmed the desired S4 placement. Here we report inhibitors with EC50 values as low as 0.080μM, while remdesivir yields values of 0.5-2μM in side-by-side testing with infectious SARS-CoV-2. A key factor in the improvement is enhanced cell permeability, as reflected in PAMPA measurements. Compounds 19 (I) and 21 (II) are particularly promising as potential therapies for COVID-19, featuring IC50 values of 0.044-0.061μM, EC50 values of ca. 0.1μM, good aqueous solubility, and no cytotoxicity.
ACS Medicinal Chemistry Letters published new progress about 1256345-74-0. 1256345-74-0 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Boronic acid and ester,Benzene,Ether,Boronic Acids,Boronic acid and ester, name is (3-Chloro-5-propoxyphenyl)boronic acid, and the molecular formula is C18H34N4O5S, SDS of cas: 1256345-74-0.
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