6-amino-3-methyl-4-(4-methylsulfanylphenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 6-amino-3-methyl-4-(4-methylsulfanylphenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
• 英文别名: 6-amino-3-methyl-4-(4-(methylthio)phenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile；6-amino-3-methyl-4-(4-methylsulfanylphenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
• 化学式: C₁₅H₁₄N₄OS
• 分子量: 298.368
• InChiKey: BVMVDAXEFZXPFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  甲酸 、 6-amino-3-methyl-4-(4-methylsulfanylphenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile 在 硫酸 作用下， 生成 3-methyl-4-(4-(methylthio)phenyl)-4,6-dihydropyrazolo-[4′,3′:5,6]pyrano-[2,3-d]pyrimidin-5(2H)-one
  参考文献：
  名称：

  新型抗糖尿病药物吡唑并吡喃并[2,3-d]-嘧啶类似物的合成、活性、对接和动态模拟研究

  摘要：

  通过针对α-葡萄糖苷酶和α-淀粉酶等两种酶靶标的比较筛选，评估了新合成的吡唑并吡喃并[2,3-]-嘧啶类似物的抗糖尿病潜力。所有新制备的分子均通过 HNMR、CNMR 和 HR-MS 分析进行表征和确认。以阿卡波糖为标准，通过α-葡萄糖苷酶和α-淀粉酶酶抑制作用筛选体外抗糖尿病活性。其中，化合物 () 表现出最有效的抗糖尿病活性，对 α-葡萄糖苷酶和 α-淀粉酶抑制的 IC 值分别为 1.18 µM 和 21.63 µM，超过了参比阿卡波糖的 IC 值 3.26 µM 和 32.21 µM 。分子结构研究表明，对位吸电子（NO）基团对于抑制活性至关重要。与参考相比，其他混合支架和 7 h 也表现出良好的抑制作用。基于 AutoDock vina 程序评分，对所有分子进行了分子对接研究，并进一步考虑用于分子动力学模拟。该研究包括蛋白质稳定性、APO-蛋白质动力学和相互作用。利用分子动力学模拟

  DOI：

  10.1016/j.molstruc.2024.137720
• 作为产物：
  描述：

  3-甲基-3-吡唑啉-5-酮 、 2-(4-(methylthio)benzylidene)malononitrile 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.03h， 以72%的产率得到6-amino-3-methyl-4-(4-methylsulfanylphenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
  参考文献：
  名称：

  Dihydropyrano [2,3-c] pyrazole: Novel in vitro inhibitors of yeast α-glucosidase

  摘要：

  Inhibition of alpha-glucosidase enzyme activity is a reliable approach towards controlling post-prandial hyperglycemia associated risk factors. During the current study, a series of dihydropyrano[ 2,3-c] pyrazoles (1-35) were synthesized and evaluated for their a-glucosidase inhibitory activity. Compounds 1, 4, 22, 30, and 33 were found to be the potent inhibitors of the yeast alpha-glucosidase enzyme. Mechanistic studies on most potent compounds reveled that 1, 4, and 30 were non-competitive inhibitors (K-i = 9.75 +/- 0.07, 46 +/- 0.0001, and 69.16 +/- 0.01 mu M, respectively), compound 22 is a competitive inhibitor (K-i = 190 +/- 0.016 mu M), while 33 was an uncompetitive inhibitor (K-i = 45 +/- 0.0014 mu M) of the enzyme. Finally, the cytotoxicity of potent compounds (i.e. compounds 1, 4, 22, 30, and 33) was also evaluated against mouse fibroblast 3T3 cell line assay, and no toxicity was observed. This study identifies non-cytotoxic novel inhibitors of alpha-glucosidase enzyme for further investigation as anti-diabetic agents. (C) 2016 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2016.01.008

文献信息

• Meglumine promoted one-pot, four-component synthesis of pyranopyrazole derivatives
  作者：Rui-Yun Guo、Zhi-Min An、Li-Ping Mo、Shu-Tao Yang、Hong-Xia Liu、Shu-Xia Wang、Zhan-Hui Zhang

  DOI：10.1016/j.tet.2013.09.082

  日期：2013.11

  catalyst for the synthesis of a series of pyranopyrazole derivatives via a one-pot, four-component reaction of carbonyl compound or isatin, hydrazine hydrate, malononitrile, and β-keto ester in EtOH–H2O. The catalyst was found to work extremely for aldehydes, ketones or isatins at room temperature to give the corresponding dihydropyrano[2,3-c]pyrazole or spiro[indoline-3,4′-pyrano[2,3-c]pyrazole] derivatives

  证明葡甲胺是一种生物基化学物质，它是通过羰基化合物或靛红，水合肼，丙二腈和β的单锅四组分反应合成一系列吡喃并吡唑衍生物的高效且可重复使用的催化剂。酮的EtOH-H酯2 O.将催化剂在室温下发现极其对醛，酮或靛红工作以得到相应的二氢吡喃并[2,3- c ^ ]吡唑或螺[二氢吲哚-3,4'-吡喃并并[2,3- c ^ ]吡唑]衍生物以高产率。这个新方法的显着特点是广泛的底物范围，室温下的反应条件，反应时间短，产量高，容易进行后处理过程中，催化剂的可重用性，并且不存在有害的有机溶剂。
• Sugarcane Bagasse Ash-Based Silica-Supported Boric Acid (SBA-SiO2-H3BO3): A Versatile and Reusable Catalyst for the Synthesis of 1,4Dihydropyrano[2,3c]pyrazole Derivatives
  作者：A. K. Pandey、A. Kumar、S. C. Shrivastava

  DOI：10.1134/s1070428021040229

  日期：2021.4

  one-pot four-component reaction of various substituted benzaldehydes, hydrazine hydrate or phenylhydrazine, ethyl acetoacetate, and malononitrile in aqueous medium in the presence of sugarcane bagasse ash-based silica-supported boric acid (SBA-SiO2-H3BO3) as a solid acid catalyst. The advantages of this methodology are the use of cost-effective and nontoxic catalyst, short reaction time, operational simplicity

  摘要 一个简单的，绿色的，高效的协议已被开发用于生物活性1,4dihydropyrano [2,3的合成Ç ]经由各种取代的苯甲醛的一锅四组分反应的吡唑衍生物，水合肼或苯肼，乙酰乙酸乙酯，和在甘蔗渣灰分基二氧化硅负载的硼酸（SBA-SiO 2 -H 3 BO 3）作为固体酸催化剂的存在下，在水性介质中制备丙二腈。这种方法的优点是使用经济高效且无毒的催化剂，反应时间短，操作简便，产率高（90-95％），二氧化硅来源的可用性和绿色方案。
• Fast synthesis of pyrano[2,3-c]pyrazoles: strong effect of Brönsted and Lewis acidic ionic liquids
  作者：Abdol R. Hajipour、Morteza Karimzadeh、Hamed Tavallaei

  DOI：10.1007/s13738-014-0561-0

  日期：2015.6

  approach, four-component synthesis of some pyrano[2,3-c]pyrazoles by [ChCl][ZnCl2]2 and [H-NMP]HSO4 as inexpensive and recyclable acidic ionic liquids were investigated. Excellent yields of products were obtained using both environmentally friendly safe ionic liquids. A comparative study of [ChCl][ZnCl2]2 as Lewis acidic ionic liquid and [H-NMP]HSO4 as Brönsted acidic ionic liquid was also carried out

  以一种独特的方法，研究了由[ChCl] [ZnCl 2 ] 2和[H-NMP] HSO 4作为廉价且可回收的酸性离子液体，对一些吡喃并[2,3- c ]吡唑进行四组分合成的方法。使用两种环境友好的安全离子液体均可获得优异的产品收率。还对作为路易斯酸性离子液体的[ChCl] [ZnCl 2 ] 2和作为布朗斯台德酸性离子液体的[H-NMP] HSO 4进行了比较研究。结果表明，与已报道的碱性离子液体相比，这些离子液体的优点是反应时间短，没有副产物和可重复使用。
• An Organobase (TBD)-Anchored Mesoporous Silica Nanoparticle-Catalyzed Green Synthesis of Dihydropyrano[2,3-c]pyrazoles
  作者：Bikash Karmakar

  DOI：10.1071/ch15812

  日期：——

  An efficient, mild, and environmental friendly method has been developed for the synthesis of dihydropyrano[2,3-c]pyrazole in ethanolic water over 1,5,7-triazabicyclo-[4,4,0]-dec-1-ene (TBD)-anchored mesoporous silica nanoparticle catalyst. The method involves the assembly of ethyl acetoacetate, hydrazine hydrate, different aldehydes, and malononitrile. It affords the corresponding product in high yield with short reaction times, while employing a very low loading of catalyst. The catalyst was reused several times without significant loss in activity.

  在 1,5,7- 三氮杂双环-[4,4,0]-癸-1-烯（TBD）锚定介孔二氧化硅纳米粒子催化剂上，开发了一种在乙醇水中合成二氢吡喃并[2,3-c]吡唑的高效、温和且环保的方法。该方法涉及乙酰乙酸乙酯、水合肼、不同的醛和丙二腈的组装。该方法能以较短的反应时间获得高产率的相应产品，同时催化剂的负载量极低。催化剂可重复使用多次，而活性不会明显降低。
• MIL-53(Fe) Metal-Organic Frameworks (MOFs) as an Efficient and Reusable Catalyst for the One-Pot Four-Component Synthesis of Pyrano[2,3-c]-pyrazoles
  作者：Mohammad Ali Ghasemzadeh、Boshra Mirhosseini-Eshkevari、Mohammad Hossein Abdollahi-Basir

  DOI：10.1002/aoc.4679

  日期：2019.1

  A novel and simple approach for the efficient and rapid synthesis of pyrano[2,3‐c]‐pyrazoleshas been accomplished via the four‐component condensation reaction of malononitrile, hydrazine hydrate, ethyl acetoacetate, and substituted aldehydes using MIL‐53(Fe) metal–organic framework (MOF) as a catalyst in ethanol at room temperature. Recycling studies have shown that the MIL‐53(Fe) can be readily recovered

  通过使用MIL-53（Fe）的丙二腈，水合肼，乙酰乙酸乙酯和取代的醛的四组分缩合反应，完成了高效快速合成吡喃并[2,3-c]-吡唑的新方法。金属-有机骨架（MOF）在室温下作为乙醇中的催化剂。回收研究表明，MIL-53（Fe）可以很容易地回收并重复使用六次，而不会显着降低其活性。本方案提供的优点包括反应时间短，后处理简单，产率高，消除了有毒溶剂，没有色谱纯化和催化剂的可回收性。此外，该催化剂还可以通过SEM，EDX，FT-IR，XRD，TGA和TEM分析得到充分表征。