Yamane, Daiki published the artcileSelective covalent targeting of SARS-CoV-2 main protease by enantiopure chlorofluoroacetamide, Recommanded Product: Pyridazine-4-carbaldehyde, the publication is Chemical Science (2022), 13(10), 3027-3034, database is CAplus and MEDLINE.
An irreversible SARS-CoV-2 Mpro inhibitor possesseschlorofluoroacetamide (CFA) as a warhead for the covalent modification of Mpro. Ugi multicomponent reaction using chlorofluoroacetic acid enabled the rapid synthesis of dipeptidic CFA derivatives RC(O)N(C6H5R1)CH(R2)C(O)NHR3 (R = Ac, ethenyl, difluoroacetyl, furan-2-yl; R1 = i-Pr, t-Bu, 1-methylcyclohexyl, etc.; R2 = pyridin-3-yl, pyridazin-4-yl, pyridazin-3-yl, etc.; R3 = t-Bu, isoquinolin-7-yl, 2-(3-fluorophenyl)ethyl, etc.) that identified (SR)/(RR)/(RS)(SS)-2-chloro-2-fluoro-N-(2-[(3-fluorophenethyl)amino]-2-oxo-1-(pyrimidin-5-yl)ethyl)-N-[4-(pentafluoro-lmbda6-sulfaneyl)phenyl]acetamide as a potent inhibitor of SARS-CoV-2 Mpro. Among the four stereoisomers, (R)-2-chloro-2-fluoro-N-((R)-2-[(3-fluorophenethyl)amino]-2-oxo-1-(pyrimidin-5-yl)ethyl)-N-[4-(pentafluoro-lamda6-sulfaneyl)phenyl]acetamide exhibited a markedly higher inhibitory activity against Mpro than the other isomers. Reaction kinetics and computational docking studies suggest that the R configuration of the CFA warhead is crucial for the rapid covalent inhibition of Mpro. These findings highlight the prominent influence of the CFA chirality on the covalent modification of proteinous cysteines and provide the basis for improving the potency and selectivity of CFA-based covalent inhibitors.
Chemical Science published new progress about 50901-42-3. 50901-42-3 belongs to pyridazine, auxiliary class Pyridazine,Aldehyde, name is Pyridazine-4-carbaldehyde, and the molecular formula is C4H8Cl2S2, Recommanded Product: Pyridazine-4-carbaldehyde.
Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem