title: Design and syntheses of novel N-(benzothiazol-5-yl)-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione and N-(benzothiazol-5-yl)isoindoline-1,3-dione as potent protoporphyrinogen oxidase inhibitors.
abstract: Discovery of protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors has been one of the hottest research areas in the field of herbicide development for many years. As a continuation of our research work on the development of new PPO-inhibiting herbicides, a series of novel N-(benzothiazol-5-yl)-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-diones (1a-p) and N-(benzothiazol-5-yl)isoindoline-1,3-diones (2a-h) were designed and synthesized according to the ring-closing strategy of two ortho-substituents. The bioassay results indicated that some newly synthesized compounds exhibited higher PPO inhibition activity than the control of sulfentrazone. Compound 1a, S-(5-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-6-fluorobenzothiazol-2-yl) O-methyl carbonothioate, was identified as the most potent inhibitor with k(i) value of 0.08 μM, about 9 times higher than that of sulfentrazone (k(i) = 0.72 μM). Further green house assay showed that compound 1b, methyl 2-((5-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-6-fluorobenzothiazol-2-yl)thio)acetate, exhibited herbicidal activity comparable to that of sulfentrazone even at a concentration of 37.5 g ai/ha. In addition, among six tested crops, wheat exhibited high tolerance to compound 1b even at a dosage of 300 g ai/ha. These results indicated that compound 1b might have the potential to be developed as a new herbicide for weed control of wheat field.
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Jiang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zuo
authors.forename: Zhi-Fang
authors.initials: ZF
authors.lastname: Wang
authors.forename: Yin
authors.initials: Y
authors.lastname: Tan
authors.forename: Qiong-You
authors.initials: QY
authors.lastname: Wu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xi
authors.forename: Guang-Fu
authors.initials: GF
authors.lastname: Yang
mesh_terms: D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006540:Herbicides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D057685:Plant Weeds / Q000187:drug effects; D050768:Protoporphyrinogen Oxidase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D006540:Herbicides; D050768:Protoporphyrinogen Oxidase