Wang, Lei published the artcileChemical profiling of HIV-1 capsid-targeting antiviral PF74, Application of 4-Methoxy-N-methylaniline, the main research area is indole peptidomimetic synthesis antiviral HIV cytotoxicity CA hexamer stability; Capsid-targeting antivirals; HIV-1; PF74.
The capsid protein (CA) of HIV-1 plays essential roles in multiple steps of the viral replication cycle by assembling into functional capsid core, controlling the kinetics of uncoating and nuclear entry, and interacting with various host factors. Targeting CA represents an attractive yet underexplored antiviral approach. Of all known CA-targeting small mol. chemotypes, the peptidomimetic PF74, I, is particularly interesting because it binds to the same pocket used by a few important host factors, resulting in highly desirable antiviral phenotypes. However, further development of I entails understanding its pharmacophore and mitigating its poor metabolic stability. We report herein the design, synthesis, and evaluation of a large number of I analogs aiming to provide a comprehensive chem. profiling of I and advance the understanding on its detailed binding mechanism and pharmacophore. The analogs, containing structural variations mainly in the aniline domain and/or the indole domain, were assayed for their effect on stability of CA hexamers, antiviral activity, and cytotoxicity. Selected analogs were also tested for metabolic stability in liver microsomes, alone or in the presence of a CYP3A inhibitor. Collectively, our studies identified important pharmacophore elements and revealed addnl. binding features of I, which could aid in future design of improved ligands to better probe the mol. basis of CA-host factor interactions, design strategies to disrupt them, and ultimately identify viable CA-targeting antiviral leads.
European Journal of Medicinal Chemistry published new progress about Anti-HIV agents. 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Application of 4-Methoxy-N-methylaniline.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem