Synthesis and Herbicidal Activity of Pyrido[2,3-d]pyrimidine-2,4-dione–Benzoxazinone Hybrids as Protoporphyrinogen Oxidase Inhibitors

To search for new protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors with improved bioactivity, a series of novel pyrido[2,3- d ]pyrimidine-2,4-dione–benzoxazinone hybrids, 9 – 13, were designed and synthesized. Several compounds with improved tobacco PPO ( mt PPO)-inhibiting and promising herbicidal activities were found. Among them, the most potent compound, 3-(7-fluoro-3-oxo-4-(prop-2-yn-1-yl)-3,4-dihydro-2 H -benzo[ b ][1,4] oxazin-6-yl)-1-methylpyrido[2,3- d ]pyrimidine-2,4(1 H,3 H )-dione, 11q, with a K i value of 0.0074 μM, showed six times more activity than flumioxazin ( K i = 0.046 μM) against mt PPO. Compound 11q displayed a strong and broad spectrum of weed control at 37.5–150 g of active ingredient (ai)/ha by both post- and pre-emergence application, which was comparable to that of flumioxazin. 11q was safe to maize, soybean, peanut, and cotton at 150 g ai/ha, and selective to rice and wheat at 75 g ai/ha by pre-emergence application, indicating potential applicability in these fields.