Zhang, Xujie published the artcileDesign, synthesis, and mechanism study of dimerized phenylalanine derivatives as novel HIV-1 capsid inhibitors, Recommanded Product: 4-Methoxy-N-methylaniline, the main research area is design synthesis mechanism study dimerized phenylalanine; HIV1 capside inhibitor phenylalanine dimer structure activity relationship; Assembly; Capsid; Dimer; HIV-1; Phenylalanine derivatives.
HIV-1 capsid (CA) plays indispensable and multiple roles in the life cycle of HIV-1, become an attractive target in antiviral therapy. Herein, we report the design, synthesis, and mechanism study of a novel series of dimerized phenylalanine derivatives as HIV-1 capsid inhibitors using 2-piperazineone or 2,5-piperazinedione as a linker. The structure-activity relationship (SAR) indicated that dimerized phenylalanines were more potent than monomers of the same chemotype. Further, the inclusion of fluorine substituted phenylalanine and methoxyl substituted aniline was found to be beneficial for antiviral activity. From the synthesized series, I was found to be the most potent compound with an EC50 value of 0.57μM, comparable to II. Interestingly, I demonstrated a slightly higher affinity to the CA monomer than the CA hexamer, commensurate with its more significant effect in the late-stage of the HIV-1 lifecycle. Competitive SPR experiments with peptides from CPSF6 and NUP153 revealed that Q-c4 binds to the interprotomer pocket of hexameric CA as designed. Single-round infection assays showed that I interferes with the HIV-1 life cycle in a dual-stage manner, affecting both pre-and post-integration. Stability assays in human plasma and human liver microsomes indicated that although I has improved stability over II, this kind of inhibitor still requires further optimization. And the results of the online molinspiration software predicted that I has desirable physicochem. properties but some properties still have some violation from the Lipinski rule of five. Overall, the dimerized phenylalanines are promising novel platforms for developing future HIV-1 CA inhibitors with considerable potential for optimization.
European Journal of Medicinal Chemistry published new progress about HIV protease inhibitors. 5961-59-1 belongs to class isoquinoline, name is 4-Methoxy-N-methylaniline, and the molecular formula is C8H11NO, Recommanded Product: 4-Methoxy-N-methylaniline.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem