Rational design of tetrahydrotetrazinones as potent nonclassical radical-trapping antioxidants for inhibition of ferroptosis.

A clear trend of increasing activity with lipophilicity was observed in the series 3a [ N ( 2 ), N (3)-dimethyl; cLogP = 1.91] < 12 [ N (2)-methyl, N (3)- n -propyl; cLogP = 2.81] < 4a [ N (2), N (3)-di-isopropyl; cLogP = 3.72], with 4a exhibiting a well-defined inhibition period ( k inh = 1.5 × 10 4 M −1 s −1 ; Fig. 4E ).

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