Synthesis and Evaluation of Aryl Quinolines as HIV-1 Integrase Multimerization Inhibitors
Chemistry and Biochemistry
HIV-1 integrase multimerization inhibitors have recently been established as an effective class of antiretroviral agents due to their potent ability to inhibit viral replication. Specifically, quinoline-based inhibitors have been shown to effectively impair HIV-1 replication, highlighting the importance of these heterocyclic scaffolds. Pursuant of our endeavors to further develop a library of quinoline-based candidates, we have implemented a structure–activity relationship study of trisubstituted 4-arylquinoline scaffolds that examined the integrase multimerization properties of substitution patterns at the 4-position of the quinoline. Compounds consisting of substituted phenyl rings, heteroaromatics, or polycyclic moieties were examined utilizing an integrase aberrant multimerization in vitro assay. para-Chloro-4-phenylquinoline 11b and 2,3-benzo[b][1,4]dioxine 15f showed noteworthy EC50 values of 0.10 and 0.08 μM, respectively.
ACS Medicinal Chemistry Letters
Jentsch, N. G.,
Hart, A. P.,
Hume, J. D.,
McNeely, K. A.,
Pigza, J. A.,
Donahue, M. G.,
Kessl, J. J.
(2018). Synthesis and Evaluation of Aryl Quinolines as HIV-1 Integrase Multimerization Inhibitors. ACS Medicinal Chemistry Letters, 9, 1007-1012.
Available at: https://aquila.usm.edu/fac_pubs/16488