3-(5-三氟乙硫基)苯基-2,3-二氢喹唑啉-4(1H)-酮类衍生物的设计、合成及杀螨活性
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摘要
[目的]发现高活性的杀螨化合物。[方法]采用骨架跃迁的策略,设计、合成了10个3-(5-三氟乙硫基)苯基-2,3-二氢喹唑啉-4(1H)-酮类新化合物,其结构经1H NMR确证,并进行杀朱砂叶螨的活性测试。[结果]生物活性数据表明,化合物7a、7b、7c、9a、9b在100 mg/L剂量下,对朱砂叶螨致死率达100%,其中化合物7b和9b在5 mg/L剂量下,对朱砂叶螨的致死率分别为97.3%和86.0%。[结论]目标化合物7b、7c、9b,在100、10 mg/L剂量下对朱砂叶螨具有令人满意的活性,其中7b和9b在5 mg/L更低剂量下对朱砂叶螨仍表现出优异的杀螨活性,值得深入研究。
[Aims] The aims were to discover new acaricidal compounds with high activity. [Methods] Ten novel3-( 5-trifluoroethylsulfanyl-phen-1-yl)-2, 3-dihydroquinazolin-4( 1 H)-one compounds were designed and prepared utilizing skeleton hopping strategy, and their structures were characterized by1 H NMR. Their acaricidal activities against Tetranychus cinnabarinus were tested. [Results] Biological activities of the target compounds showed that the mortality rates of compounds 7 a, 7 b, 7 c, 9 a and 9 b against T. cinnabarinus at 100 mg/L were all 100%. Among them,the mortality rates of 7 b and 9 b at 5 mg/L were 97.3 and 86.0%, respectively. [Conclusions] The target compounds 7 b,7 c and 9 b possessed satisfied acaricidal activities at 100 and 10 mg/L, especially compounds 7 b and 9 b exhibited excellent acaricidal activities even at lower concentration of 5 mg/L, which are worth further study.
[Aims] The aims were to discover new acaricidal compounds with high activity. [Methods] Ten novel3-( 5-trifluoroethylsulfanyl-phen-1-yl)-2, 3-dihydroquinazolin-4( 1 H)-one compounds were designed and prepared utilizing skeleton hopping strategy, and their structures were characterized by1 H NMR. Their acaricidal activities against Tetranychus cinnabarinus were tested. [Results] Biological activities of the target compounds showed that the mortality rates of compounds 7 a, 7 b, 7 c, 9 a and 9 b against T. cinnabarinus at 100 mg/L were all 100%. Among them,the mortality rates of 7 b and 9 b at 5 mg/L were 97.3 and 86.0%, respectively. [Conclusions] The target compounds 7 b,7 c and 9 b possessed satisfied acaricidal activities at 100 and 10 mg/L, especially compounds 7 b and 9 b exhibited excellent acaricidal activities even at lower concentration of 5 mg/L, which are worth further study.
引文
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[10] XING Jun-hao, YANG Ling-yun, YANG Yi-fei, et al.Design, Synthesis and Biological Evaluation of Novel2,3-Dihydroquinazolin-4(1H)-one Derivatives as Potential f Xa Inhibitors[J]. Eur J Med Chem, 2017, 125:411-422.
[2] ITO Y, NAKANO Y. Pest Control Agent Composition and Pest Controlling Method:WO, 2009022548[P]. 2009-02-19.
[3] STEFFEN G, KARSTEN K, WOLFGANG V D, et al.3-Arylquinazolin-4-one Compounds for Combating Invertebrate Pests:WO, 2010100189[P]. 2010-09-10.
[4] ORIYABE K, YAMAGUCHI M, ITOU Y, et al. 3-Triazolylphenyl Sulfide Derivative and Insecticide/acaricide/nematicide Containing the Same as Active Ingredient:WO, 2006043635[P]. 2006-04-27.
[5]徐利保,李鹏,张立新,等. 3-苯基硫醚-1,2,3-苯并三嗪-4-酮类衍生物的设计、合成及杀螨活性[J].农药, 2018, 57(10):706-709.
[6] ALTMANN K H, BOLD G, FURET P, et al. N-Aryl(thio)Anthranilic Acid Amide Derivatives, Their Preparation and Their Use as VEGF Receptor Tyrosine Kinase Inhibitors:US,20030064992[P]. 2003-04-03.
[7] KAKUTA H, TANATANI A, NAGASAWA K, et al. Specific Nonpeptide Inhibitors of Puromycin-sensitive Aminopeptidase with a 2,4(1H,3H)-Quinazolinedione Skeleton[J]. Chem Pharm Bull, 2003, 51(11):1273-1282.
[8] MALANCONA S, DONGHI M, FERRARA M, et al. Allosteric Inhibitors of Hepatitis C Virus NS5B Polymerase Thumb Domain Site II:Structure-based Design and Synthesis of New Templates[J]. Bioorg Med Chem, 2010, 18(8):2836-2848.
[9] NUMADATE A, MITA Y, MATSUMOTO Y, et al. Development of 2-Thioxoquinazoline-4-one Derivatives as Dual and Selective Inhibitors of Dynamin-related Protein 1(Drp1)and Puromycinsensitive Aminopeptidase(PSA)[J]. Chem Pharm Bull, 2014, 62(10):979-988.
[10] XING Jun-hao, YANG Ling-yun, YANG Yi-fei, et al.Design, Synthesis and Biological Evaluation of Novel2,3-Dihydroquinazolin-4(1H)-one Derivatives as Potential f Xa Inhibitors[J]. Eur J Med Chem, 2017, 125:411-422.