Sherrill, Lavinia M.; Joya, Elva E.; Walker, AnnMarie; Roy, Anuradha; Alhammad, Yousef M.; Atobatele, Moriama; Wazir, Sarah; Abbas, George; Keane, Patrick; Zhuo, Junlin; Leung, Anthony K. L.; Johnson, David K.; Lehtio, Lari; Fehr, Anthony R.; Ferraris, Dana published the artcile< Design, synthesis and evaluation of inhibitors of the SARS-CoV-2 nsp3 macrodomain>, HPLC of Formula: 2743-40-0, the main research area is SARS CoV2 coronavirus nsp3 macrodomain inhibitor COVID19; ADP-ribosylation; COVID-19; Coronavirus; Nsp3 macrodomain inhibitors; SARS-CoV-2.
A series of amino acid based 7H-pyrrolo[2,3-d]pyrimidines were designed and synthesized to discern the structure activity relationships against the SARS-CoV-2 nsp3 macrodomain (Mac1), an ADP-ribosylhydrolase that is critical for coronavirus replication and pathogenesis. Structure activity studies identified compound 15c as a low-micromolar inhibitor of Mac1 in two ADP-ribose binding assays. This compound also demonstrated inhibition in an enzymic assay of Mac1 and displayed a thermal shift comparable to ADPr in the melting temperature of Mac1 supporting binding to the target protein. A structural model reproducibly predicted a binding mode where the pyrrolo pyrimidine forms a hydrogen bonding network with Asp22 and the amide backbone NH of Ile23 in the adenosine binding pocket and the carboxylate forms hydrogen bonds to the amide backbone of Phe157 and Asp156, part of the oxyanion subsite of Mac1. Compound 15c also demonstrated notable selectivity for coronavirus macrodomains when tested against a panel of ADP-ribose binding proteins. Together, this study identified several low MW, low 渭M Mac1 inhibitors to use as small mol. chem. probes for this potential anti-viral target and offers starting points for further optimization.
Bioorganic & Medicinal Chemistry published new progress about Anticoronaviral agents. 2743-40-0 belongs to class esters-buliding-blocks, and the molecular formula is C8H18ClNO2, HPLC of Formula: 2743-40-0.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics