title: Design, synthesis and herbicidal activity of novel quinazoline-2,4-diones as 4-hydroxyphenylpyruvate dioxygenase inhibitors.
abstract: BACKGROUND
  4-Hydroxyphenylpyruvate dioxygenase (HPPD) (EC 1.13.11.27) has been identified as one of the most promising target sites for herbicide discovery. To discover novel HPPD inhibitors with high herbicidal activity and improved crop selectivity, a series of novel triketone-containing quinazoline-2,4-dione derivatives possessing a variety of substituents at the N-1 position of the quinazoline-2,4-dione ring were designed and synthesised.
  
  
  RESULTS
  The results of in vitro tests and greenhouse experiments indicated that some analogues showed good HPPD inhibitory activity, with promising broad-spectrum herbicidal activity at a rate of 150 g AI ha(-1) . Most surprisingly, compound 11 h, 1-ethyl-6-(2-hydroxy-6-oxocyclohex-1-enecarbonyl)-3-(o-tolyl)quinazoline-2,4(1H,3H)-dione, showed the highest HPPD inhibition activity, with a Ki value of 0.005 μM, about 2 times more potent than mesotrione (Ki  = 0.013 μM). Further greenhouse experiments indicated that compounds 11d and 11 h displayed strong and broad-spectrum post-emergent herbicidal activity even at a dosage as low as 37.5 g AI ha(-1) , which was superior to mesotrione. More importantly, compounds 11d and 11 h were safe for maize at a rate of 150 g AI ha(-1) , and compound 11d was safe for wheat as well.
  
  
  CONCLUSIONS
  The present work indicated that the triketone-containing quinazoline-2,4-dione motif could be a potential lead structure for further development of novel herbicides.
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, College of Chemistry, Central China Normal University, Wuhan, China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Wang
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, College of Chemistry, Central China Normal University, Wuhan, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, College of Chemistry, Central China Normal University, Wuhan, China.
authors.forename: Run-Jie
authors.initials: RJ
authors.lastname: Cao
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, College of Chemistry, Central China Normal University, Wuhan, China.
authors.forename: Ze-Zhong
authors.initials: ZZ
authors.lastname: Ming
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, College of Chemistry, Central China Normal University, Wuhan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, College of Chemistry, Central China Normal University, Wuhan, China.
authors.forename: Ge-Fei
authors.initials: GF
authors.lastname: Hao
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, College of Chemistry, Central China Normal University, Wuhan, China.
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Yang
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, College of Chemistry, Central China Normal University, Wuhan, China.|Collaborative Innovation Centre of Chemical Science and Engineering, Tianjin, China.
authors.forename: Guang-Fu
authors.initials: GF
authors.lastname: Yang
mesh_terms: D015111:4-Hydroxyphenylpyruvate Dioxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D017360:Arabidopsis / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D029681:Arabidopsis Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006540:Herbicides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D029681:Arabidopsis Proteins; D006540:Herbicides; D011799:Quinazolines; D015111:4-Hydroxyphenylpyruvate Dioxygenase
keywords: 4-hydroxyphenylpyruvate dioxygenase; herbicide; quinazoline-2,4-dione; structure-activity relationship; weed control