title: Design and synthesis of 1-(benzothiazol-5-yl)-1H-1,2,4-triazol-5-ones as protoporphyrinogen oxidase inhibitors.
abstract: Protoporphyrinogen oxidase (PPO, E.C. 1.3.3.4) is the action target for several structurally diverse herbicides. A series of novel 4-(difluoromethyl)-1-(6-halo-2-substituted-benzothiazol-5-yl)-3-methyl-1H-1,2,4-triazol-5(4H)-ones 2a-z were designed and synthesized via the ring-closure of two ortho-substituents. The in vitro bioassay results indicated that the 26 newly synthesized compounds exhibited good PPO inhibition effects with K(i) values ranging from 0.06 to 17.79 μM. Compound 2e, ethyl 2-{[5-(4-(difluoromethyl)-3-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-6-fluorobenzo-thiazol-2-yl]thio}acetate, was the most potent inhibitor with K(i) value of 0.06 μM against mtPPO, comparable to (K(i)=0.03 μM) sulfentrazone. Further green house assays showed that compound 2f (K(i)=0.24 μM, mtPPO), ethyl 2-{[5-(4-(difluoromethyl)-3-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-6-fluorobenzothiazol-2-yl]thio}propanoate, showed the most promising post-emergence herbicidal activity with broad spectrum even at concentrations as low as 37.5 gai/ha. Soybean exhibited tolerance to compound 2f at the dosages of 150 gai/ha, whereas they are susceptible to sulfentrazone even at 75 gai/ha. Thus, compound 2f might be a potential candidate as a new herbicide for soybean fields.
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zuo
authors.forename: Sheng-Gang
authors.initials: SG
authors.lastname: Yang
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Luo
authors.forename: Ying
authors.initials: Y
authors.lastname: Tan
authors.forename: Ge-Fei
authors.initials: GF
authors.lastname: Hao
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: D001681:Biological Assay; D006540:Herbicides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D062105:Molecular Docking Simulation; D010940:Plant Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D057685:Plant Weeds / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D050768:Protoporphyrinogen Oxidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013025:Glycine max / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology
chemical_list: D006540:Herbicides; D010940:Plant Proteins; D013449:Sulfonamides; D013844:Thiazoles; D014230:Triazoles; C475571:N-(2,4-dichloro-5-(4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenyl)methanesulfonamide; D050768:Protoporphyrinogen Oxidase