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To identify low-dose PPO-inhibiting leads, 41 benzyl-substituted pyrimidinedione derivatives were designed by side-chain optimization of epyrifenacil and synthesized. In greenhouse postemergence screening, FM-604 provided 100% control of Zinnia elegans and Abutilon theophrasti and 80\u201385% control of Setaria glauca and Echinochloa crus-galli at the lowest rate tested (2.34 g a.i.\/ha). FM-604 inhibited Nicotiana tabacum PPO with an IC50 of 21.46 nM versus 30.29 nM for epyrifenacil. Docking and 100 ns molecular dynamics simulations suggested a stable binding mode involving Arg98, Asn67, and Phe392, while DFT calculations indicated a comparatively small HOMO\u2013LUMO gap. These results identify FM-604 as a PPO-inhibiting lead for further optimization and evaluation.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c06281","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:01:35Z","timestamp":1789138895000},"page":"29242-29251","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of FM-604,\na Benzyl-Substituted Pyrimidinedione\nPPO Inhibitor with Potent Postemergence Herbicidal Activity"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0151-7978","authenticated-orcid":true,"given":"Jialin","family":"Ye","sequence":"first","affiliation":[{"name":"Shenyang University of Chemical Technology , , ,","place":["Shenyang, China, 110142"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6541-9131","authenticated-orcid":true,"given":"Hongyan","family":"Pei","sequence":"additional","affiliation":[{"name":"Shenyang University of Chemical Technology , , ,","place":["Shenyang, China, 110142"]},{"name":"Shenyang University of Technology , , , ,","place":["Shenyang, Liaoning, China, 110870"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3749-6527","authenticated-orcid":true,"given":"Dongdong","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenyang University of Chemical Technology , , ,","place":["Shenyang, China, 110142"]},{"name":"University of Science and Technology Liaoning , , , ,","place":["Anshan, Liaoning, China, 114051"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3446-1116","authenticated-orcid":true,"given":"Yixing","family":"Gao","sequence":"additional","affiliation":[{"name":"Shenyang University of Chemical Technology , , ,","place":["Shenyang, China, 110142"]},{"name":"Shenyang University of Technology , , , ,","place":["Shenyang, Liaoning, China, 110870"]},{"name":"Metisa Biotechnology Co, Ltd. , ,","place":["Nanning, China, 530000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4952-3550","authenticated-orcid":true,"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenyang University of Chemical Technology , , ,","place":["Shenyang, China, 110142"]},{"name":"University of Science and Technology Liaoning , , , ,","place":["Anshan, Liaoning, China, 114051"]},{"name":"Metisa Biotechnology Co, Ltd. , ,","place":["Nanning, China, 530000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenyang University of Chemical Technology , , ,","place":["Shenyang, China, 110142"]},{"name":"Shenyang University of Technology , , , ,","place":["Shenyang, Liaoning, China, 110870"]},{"name":"University of Science and Technology Liaoning , , , ,","place":["Anshan, Liaoning, China, 114051"]},{"name":"Metisa Biotechnology Co, Ltd. , ,","place":["Nanning, China, 530000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"2026092310082492200_cit1","doi-asserted-by":"publisher","first-page":"17191","DOI":"10.1021\/acs.jafc.4c01389","article-title":"Design, synthesis,\nand herbicidal activity of novel tetrahydrophthalimide derivatives\ncontaining oxadiazole\/thiadiazole moieties","volume":"72","author":"Geng","year":"2024","journal-title":"J. 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