Wang, Lei published the artcileNovel HIV-1 capsid-targeting small molecules of the PF74 binding site, Related Products of isoquinoline, the main research area is HIV1 capsid targeting antiviral PF74 binding site; Capsid-targeting antivirals; HIV-1; Metabolic stability; PF74.
The PF74 (I) binding site in HIV-1 capsid protein (CA) is a compelling antiviral drug target. Although PF74 confers mechanistically distinct antiviral phenotypes by competing against host factors for CA binding, it suffers from prohibitively low metabolic stability. Therefore, there has been increasing interest in designing novel sub-chemotypes of PF74 with similar binding mode and improved metabolic stability. We report herein our efforts to explore the inter-domain interacting indole moiety for designing novel CA-targeting small mols. Our design includes simple substitution on the indole ring, and more importantly, novel sub-chemotypes with the indole moiety replaced with a few less electron-rich rings. All 56 novel analogs were synthesized and evaluated for antiviral activity, cytotoxicity, and impact on CA hexamer stability. Selected analogs were tested for metabolic stability in liver microsomes. Mol. modeling was performed to verify compound binding to the PF74 site. In the end, 5-hydroxyindole analogs (8,9 and 12, II – IV, resp.) showed improved potency (up to 20-fold) over PF74. Of the novel sub-chemotypes, α- and β-naphthyl analogs (27 and 33, V and VI, resp.) exhibited sub micromolar antiviral potencies comparable to that of PF74. Interestingly, although only moderately inhibiting HIV-1 (single-digit micromolar EC50s), analogs of the 2-indolone sub-chemotype consistently lowered the m.p. (Tm) of CA hexamers, some with improved metabolic stability over PF74.
European 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, Related Products of isoquinoline.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem