Sun, Lin published the artcileDesign, Synthesis, and Mechanism Study of Benzenesulfonamide-Containing Phenylalanine Derivatives as Novel HIV-1 Capsid Inhibitors with Improved Antiviral Activities, Product Details of C8H11NO, the main research area is amino acid benzenesulfonamide phenylalanine antiviral structure activity HIV1 pharmacokinetic; anti AIDS agent CA protein inhibitor MD simulation virion; mol docking hydrogen bond benzenesulfonamide phenylalanine metabolic stability; peptidomimetic peptide coupling drug design toxicity.
HIV-1 CA protein has gained remarkable attention as a promising therapeutic target for the development of new antivirals, due to its pivotal roles in HIV-1 replication (structural and regulatory). Herein, we report the design and synthesis of three series of benzenesulfonamide-containing phenylalanine derivatives obtained by further structural modifications of PF-74 to aid in the discovery of more potent and drug-like HIV-1 CA inhibitors. Structure-activity relationship studies of these compounds led to the identification of new phenylalanine derivatives with a piperazinone moiety, represented by compound (I), which exhibited anti-HIV-1NL4-3 activity 5.78-fold better than PF-74. Interestingly, I also showed anti-HIV-2ROD activity (EC50 = 31 nΜ), with almost 120 times increased potency over PF-74. However, due to the higher significance of HIV-1 as compared to HIV-2 for the human population, this manuscript focused on the mechanism of action of our compounds in the context of HIV-1. SPR studies on representative compounds confirmed CA as the binding target. The action stage determination assay demonstrated that these inhibitors exhibited antiviral activities with a dual-stage inhibition profile. The early-stage inhibitory activity of compound I was 6.25 times more potent as compared to PF-74, but appears to work via accelerating capsid core assembly rather than stabilization. However, the mechanism by which they exert their antiviral activity in the late-stage appears to be the same as PF-74 with less infectious HIV-1 virions are produced in their presence as judged p24 content studies. MD simulations provided the key rationale for the promising antiviral potency of I. Addnl., I exhibited modest increase in HLM and human plasma metabolic stabilities as compared to PF-74, as well as moderately improved pharmacokinetic profile, favorable oral bioavailability, and no acute toxicity. These studies provide insights and serves as a starting point for subsequent medicinal chem. efforts in optimizing these promising HIV inhibitors.
Journal of Medicinal Chemistry published new progress about AIDS (disease). 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Product Details of C8H11NO.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem