NNRT-IN-13 is a potent non-nucleoside reverse transcriptase (NNRT) inhibitor that directly suppresses HIV-1 reverse transcriptase with an IC₅₀ of 0.25 μM. It exhibits excellent antiviral activity against wild-type HIV-1 (EC₅₀= 0.0046 μM) and various resistant mutants. NNRT-IN-13 also demonstrates favorable in vivo metabolism and safety, making it useful for HIV-related research.

NNRT-IN-13 (compound 15k) demonstrates excellent antiviral activity against wild-type HIV-1 (EC₅₀ = 0.0046 μM) and exhibits broad-spectrum efficacy against several resistant mutants, such as L100I (0.0053 μM), K103N (0.0034 μM), Y181C (0.010 μM), Y188L (0.026 μM), E138K (0.015 μM), F227L/V106A (0.033 μM), and K103N/Y181C (0.029 μM), while showing low cytotoxicity in MT-4 cells (CC₅₀ = 26.64 μM). This compound binds uniquely to HIV-1 reverse transcriptase in a "Y"-shaped mode, forming novel hydrogen bonds with residues E138 and K101 at the p51-p66 interface. Additionally, NNRT-IN-13 does not inhibit CYP1A2, CYP2C9, CYP2C19, and CYP2D6 (IC₅₀ values all greater than 50 μM) and shows only weak inhibition of CYP3A4 (IC₅₀ = 13.6 μM).

NNRT-IN-13, administered intraperitoneally at doses of 50 and 2000 mg/kg, either as a single dose or every other day for 14 days, exhibited no toxic reactions or organ damage in Kunming mice.