高等学校化学学报

高等学校化学学报

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3-甲基-1-苯基-4-{4-([5-甲基-2-(4-取代芳基)-噁唑-4-基]甲氧基)-芳亚甲(苄)基}-2-吡唑啉-5-酮的设计、合成与降血糖活性

刘星1, 王亚楼1, 巫冠中2, 李江川1, 吴晓燕1   

    1. 中国药科大学药物化学教研室,
    2. 药理教研室, 南京 210009
  • 收稿日期:2006-04-21 修回日期:1900-01-01 出版日期:2007-04-10 发布日期:2007-04-10
  • 通讯作者: 王亚楼

Design, Synthesis and Hypoglycemic Activity of 3-Methyl-1-phenyl-4-{4-[(5-methyl-2-phenyloxazol-4-yl)methoxy] benzylene(benzyl)}-2-pyrazol-5-one

LIU Xing1, WANG Ya-Lou1*, WU Guan-Zhong2, LI Jiang-Chuan1, WU Xiao-Yan1   

    1. Department of Medicinal Chemistry,
    2. Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China
  • Received:2006-04-21 Revised:1900-01-01 Online:2007-04-10 Published:2007-04-10
  • Contact: WANG Ya-Lou

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被引次数

18

摘要： 设计合成了具有降血糖活性的3-甲基-1-苯基-4-[4-[[5-甲基-2-(4-取代芳基)-噁唑-4-基]甲氧基]-芳亚甲(苄)基]}-2-吡唑啉-5-酮类化合物. 用丁二酮单肟和(取代的)苯甲醛环合、氯化得到氯甲基噁唑衍生物, 与对羟基苯甲醛或香兰醛缩合, 再与3-甲基-1-苯基-2-吡唑啉-5-酮进行Knoevenagel反应及催化氢化得到目标化合物(Ⅰ和Ⅱ), 共合成了16个未见文献报道的新化合物, 并利用元素分析、IR、MS和 1H NMR确证了化合物的结构. 初步药理试验结果表明, 所合成的化合物有抑制血糖升高的倾向以及能明显加强和延长外源性胰岛素的降血糖作用, 其中化合物Ⅰb, Ⅰd和Ⅰf尤为突出, 说明这类化合物可能有增强胰岛素敏感性的作用.

关键词: 吡唑啉酮衍生物, 合成, 降血糖活性, 胰岛素增敏剂

Abstract: Based on the SAR of TZDs, 3-methyl-1-phenyl-2-pyrazoline-5-one was selected as a substitute for TZD, 3-methyl-1-phenyl-4-{4-[(5-methyl-2-phenyloxazol-4-yl)methoxy]benzylene(benzyl)}-2-pyrazol-5-one compounds were designed and synthesized in order to find some more hypoglycemic active agents and further investigate the SAR of this class of compounds. The butanedione monoxime reacted with(substituted ) benzaldehyde via cyclization and chlorination to give 4-(chloromethyl)-5-methyl-2-phenyloxazole derivatives, which condensed with 4-hydroxybenzaldehyde or vanillin, and then followed by Knoevenagel reaction with 3-methyl-1-phenyl-2-pyrazol-5-one to give compounds Ⅰa—Ⅰh. Compounds Ⅰa—Ⅰh were hydrogenated with Pa-C to give Ⅱa—Ⅱh, and their hypoglycemic activity were evaluated with glucose oxidase kit and insulin load test on normal mouse. Sixteen new target compounds were synthesized. All the compounds were characterized by 1H NMR, IR, MS and elemental analysis. The preliminary pharmacological test shows that the compounds have a good hypoglycemic activity and can enhance the action of insulin, especially Ib, Id and If.

Key words: Pyrazolone derivative, Synthesis, Hypoglycemic activity, Insulin sensitizers

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