Sahani, Rajkumar Lalji; Diana-Rivero, Raquel; Vernekar, Sanjeev Kumar V.; Wang, Lei; Du, Haijuan; Zhang, Huanchun; Castaner, Andres Emanuelli; Casey, Mary C.; Kirby, Karen A.; Tedbury, Philip R.; Xie, Jiashu; Sarafianos, Stefan G.; Wang, Zhengqiang published the artcile< Design, synthesis and characterization of HIV-1 CA-targeting small molecules: conformational restriction of PF74>, Computed Properties of 53636-56-9, the main research area is indolyl pyridyl amide preparation antiviral SAR cytotoxicity mol docking; imidazolyl indolyl amide preparation antiviral SAR cytotoxicity mol docking; HIV-1; PF74; capsid protein; conformational constraint; metabolic stability.
Designed and synthesized three series of PF74-like analogs featuring conformational constraints at the aniline terminus or the phenylalanine carboxamide moiety, and characterized them using a biophys. thermal shift assay (TSA), cell-based antiviral and cytotoxicity assays, and in vitro metabolic stability assays in human and mouse liver microsomes. These studies showed that the two series with the phenylalanine carboxamide moiety replaced by a pyridine or imidazole ring can provide viable hits. Subsequent SAR identified an improved analog I which effectively inhibited HIV-1 (EC50 = 0.31μM), strongly stabilized CA hexamer (ΔTm = 8.7°C), and exhibited substantially enhanced metabolic stability (t1/2 = 27 min for 15 vs. 0.7 min for PF74). Metabolic profiles from the microsomal stability assay also indicate that blocking the C5 position of the indole ring could lead to increased resistance to oxidative metabolism
Viruses published new progress about Amides Role: PAC (Pharmacological Activity), PRP (Properties), RCT (Reactant), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), RACT (Reactant or Reagent), PREP (Preparation), USES (Uses). 53636-56-9 belongs to class pyridine-derivatives, and the molecular formula is C7H6BrNO2, Computed Properties of 53636-56-9.