4-hydroxy-3-{3-[5-hydroxy-2-methyl-2-(4-methyl-pent-3-enyl)-2H-chromen-6-yl]-3-oxopropenyl}-benzaldehyde | 1416512-12-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 4-hydroxy-3-{3-[5-hydroxy-2-methyl-2-(4-methyl-pent-3-enyl)-2H-chromen-6-yl]-3-oxopropenyl}-benzaldehyde
• 英文别名: 4-hydroxy-3-[3-[5-hydroxy-2-methyl-2-(4-methylpent-3-enyl)chromen-6-yl]-3-oxoprop-1-enyl]benzaldehyde
• CAS: 1416512-12-3
• 化学式: C₂₆H₂₆O₅
• 分子量: 418.489
• InChiKey: QAPVRJDACKNXKJ-UHFFFAOYSA-N

物化性质

• 熔点：
  105-108 °C
• 沸点：
  623.6±55.0 °C(predicted)
• 密度：
  1.213±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.72
• 重原子数：
  31.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  83.83
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-hydroxy-3-{3-[5-hydroxy-2-methyl-2-(4-methyl-pent-3-enyl)-2H-chromen-6-yl]-3-oxopropenyl}-benzaldehyde 在 sodium tetrahydroborate 、 nickel(II) chloride hexahydrate 作用下， 以 甲醇 为溶剂， 反应 0.25h， 以60%的产率得到4-Hydroxy-3-[3-[5-hydroxy-2-methyl-2-(4-methylpent-3-enyl)chromen-6-yl]-3-oxo-propyl]benzaldehyde
  参考文献：
  名称：

  al作为抗疟药的结构与活性关系的合成与认识

  摘要：

  从中国甘草的根中分离得到的Licochalcone A（I）是迄今为止报道的最有前途的抗疟化合物。在继续我们的药物发现计划时，我们从猪屎豆属中分离了两个类似的查耳酮，medicageninin（II）和munchiwarin（III），它们对恶性疟原虫具有抗疟活性。合成了88个查耳酮的文库，并对其体外抗疟活性进行了评估。在这些中，67，68，74，77，和78显示出在体外对抗疟疾活性良好恶性疟原虫具有低细胞毒性的3D7和K1菌株。这些查耳酮还显示出寄生虫约瑟氏疟原虫（N-67株）感染的瑞士小鼠的寄生虫病减少和存活时间增加。药代动力学研究表明，不良的ADME特性导致口服生物利用度低。分子对接研究揭示了这些抑制剂在falcipain-2（FP-2）酶的活性位点的结合方向。化合物67，68，和78显示出对主要血红蛋白降解半胱氨酸适度抑制活性蛋白酶FP-2。

  DOI：

  10.1021/jm300588j
• 作为产物：
  描述：

  2,4-二羟基苯乙酮 在 吡啶 作用下， 生成 4-hydroxy-3-{3-[5-hydroxy-2-methyl-2-(4-methyl-pent-3-enyl)-2H-chromen-6-yl]-3-oxopropenyl}-benzaldehyde
  参考文献：
  名称：

  Synthesis, Structure–Activity Relationships, and Biological Studies of Chromenochalcones as Potential Antileishmanial Agents

  摘要：

  Antileishmanial activities of a library of synthetic chalcone analogues have been examined. Among them, five compounds (11, 14, 16, 17, 22, and 24) exhibited better activity than the marketed drug miltefosine in in vitro studies against the intracellular amastigotes form of Leishmania donovani. Three promising compounds, 16, 17, and 22, were tested in a L. donovani/hamster model. Oral administration of chalcone 16, at a concentration of 100 mg/kg of body weight per day for 5 consecutive days, resulted in >84% parasite inhibition at day 7 post-treatment and it retained the activity until day 28. The molecular and immunological studies revealed that compound 16 has a dual nature to act as a direct parasite killing agent and as a host immunostimulant. Pharmacokinetics and serum albumin binding studies also suggest that compound 16 has the potential to be a candidate for the treatment of the nonhealing form of leishmaniasis.

  DOI：

  10.1021/jm401893j

文献信息

• Synthesis and Insight into the Structure–Activity Relationships of Chalcones as Antimalarial Agents
  作者：Narender Tadigoppula、Venkateswarlu Korthikunta、Shweta Gupta、Papireddy Kancharla、Tanvir Khaliq、Awakash Soni、Rajeev Kumar Srivastava、Kumkum Srivastava、Sunil Kumar Puri、Kanumuri Siva Rama Raju、Wahajuddin、Puran Singh Sijwali、Vikash Kumar、Imran Siddiqi Mohammad

  DOI：10.1021/jm300588j

  日期：2013.1.10

  licorice, is the most promising antimalarial compound reported so far. In continuation of our drug discovery program, we isolated two similar chalcones, medicagenin (II) and munchiwarin (III), from Crotalaria medicagenia, which exhibited antimalarial activity against Plasmodium falciparum. A library of 88 chalcones were synthesized and evaluated for their in vitro antimalarial activity. Among these, 67,

  从中国甘草的根中分离得到的Licochalcone A（I）是迄今为止报道的最有前途的抗疟化合物。在继续我们的药物发现计划时，我们从猪屎豆属中分离了两个类似的查耳酮，medicageninin（II）和munchiwarin（III），它们对恶性疟原虫具有抗疟活性。合成了88个查耳酮的文库，并对其体外抗疟活性进行了评估。在这些中，67，68，74，77，和78显示出在体外对抗疟疾活性良好恶性疟原虫具有低细胞毒性的3D7和K1菌株。这些查耳酮还显示出寄生虫约瑟氏疟原虫（N-67株）感染的瑞士小鼠的寄生虫病减少和存活时间增加。药代动力学研究表明，不良的ADME特性导致口服生物利用度低。分子对接研究揭示了这些抑制剂在falcipain-2（FP-2）酶的活性位点的结合方向。化合物67，68，和78显示出对主要血红蛋白降解半胱氨酸适度抑制活性蛋白酶FP-2。
• Synthesis, Structure–Activity Relationships, and Biological Studies of Chromenochalcones as Potential Antileishmanial Agents
  作者：Rahul Shivahare、Venkateswarlu Korthikunta、Hardik Chandasana、Manish K. Suthar、Pragati Agnihotri、Preeti Vishwakarma、Telaprolu K. Chaitanya、Papireddy Kancharla、Tanvir Khaliq、Shweta Gupta、Rabi Sankar Bhatta、J. Venkatesh Pratap、Jitendra K. Saxena、Suman Gupta、Narender Tadigoppula

  DOI：10.1021/jm401893j

  日期：2014.4.24

  Antileishmanial activities of a library of synthetic chalcone analogues have been examined. Among them, five compounds (11, 14, 16, 17, 22, and 24) exhibited better activity than the marketed drug miltefosine in in vitro studies against the intracellular amastigotes form of Leishmania donovani. Three promising compounds, 16, 17, and 22, were tested in a L. donovani/hamster model. Oral administration of chalcone 16, at a concentration of 100 mg/kg of body weight per day for 5 consecutive days, resulted in >84% parasite inhibition at day 7 post-treatment and it retained the activity until day 28. The molecular and immunological studies revealed that compound 16 has a dual nature to act as a direct parasite killing agent and as a host immunostimulant. Pharmacokinetics and serum albumin binding studies also suggest that compound 16 has the potential to be a candidate for the treatment of the nonhealing form of leishmaniasis.