Design, synthesis, and 3D-QSAR analysis of novel 1,3,4-oxadiazol-2(3H)-ones as protoporphyrinogen oxidase inhibitors.
Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) has been identified as one of the most significant action targets for a large chemically diverse family of herbicides that exhibit some interesting characteristics, such as low use rate, low toxicity to mammals, and low environmental impact. As a continuation of research work on the development of new PPO inhibitors, some benzothiazole analogues of oxadiargyl, an important PPO-inhibiting commercial herbicide, were designed and synthesized by ring-closing of the substituents at the C-4 and C-5 positions. The bioassay results indicated that the series 8, 9, and 10 have good PPO inhibition activity with k(i) values ranging from 0.25 to 18.63 microM. Most interestingly, 9l, ethyl 2-((5-(5-tert-butyl-2-oxo-1,3,4-oxadiazol-2(3H)-yl)-6-fluorobenzothiazol-2-yl)sulfanyl) propanoate, was identified as the most promising candidate due to its high PPO inhibition effect (k(i) = 1.42 microM) and broad spectrum postemergence herbicidal activity at the concentration of 37.5 g of ai/ha.
Jiang
Li-Li
LL
Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, People's Republic of China.
Tan
Ying
Y
Zhu
Xiao-Lei
XL
Wang
Zhi-Fang
ZF
Zuo
Yang
Y
Chen
Qiong
Q
Xi
Zhen
Z
Yang
Guang-Fu
GF
D001681:Biological Assay; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D050768:Protoporphyrinogen Oxidase / Q000037:antagonists & inhibitors*; D021281:Quantitative Structure-Activity Relationship; D021241:Spectrometry, Mass, Electrospray Ionization
D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D050768:Protoporphyrinogen Oxidase; C547731:oxadiargyl