methyl 4-(((2-(1H-indol-3-yl)ethyl)amino)methyl)benzoate | 851365-06-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: methyl 4-(((2-(1H-indol-3-yl)ethyl)amino)methyl)benzoate
• 英文别名: 4-{[2-(1H-Indol-3-yl)-ethylamino]-methyl}benzoic acid methyl ester；methyl 4-[[2-(1H-indol-3-yl)ethylamino]methyl]benzoate
• CAS: 851365-06-5
• 化学式: C₁₉H₂₀N₂O₂
• 分子量: 308.38
• InChiKey: KOADSVKTLQWURJ-UHFFFAOYSA-N

物化性质

• 沸点：
  508.5±40.0 °C(Predicted)
• 密度：
  1.192±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  54.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 4-(((2-(1H-indol-3-yl)ethyl)amino)methyl)benzoate 在 羟胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 16.5h， 生成 4-((1-(2-(1H-indol-3-yl)ethyl)-3-(2-methoxyphenyl)ureido)methyl)-N-hydroxybenzamide
  参考文献：
  名称：

  Selective Histone Deacetylase 6 Inhibitors Bearing Substituted Urea Linkers Inhibit Melanoma Cell Growth

  摘要：

  The incidence of malignant melanoma has dramatically increased in recent years thus requiring the need for improved therapeutic strategies. In our efforts to design selective histone deactylase inhibitors (HDACI), we discovered that the aryl urea 1 is a modestly potent yet nonselective inhibitor. Structure-activity relationship studies revealed that adding substituents to the nitrogen atom of the urea so as to generate compounds bearing a branched linker group results in increased potency and selectivity for HDAC6. Compound 5g shows low nanomolar inhibitory potency against HDAC6 and a selectivity of similar to 600-fold relative to the inhibition of HDACI. These HDACIs were evaluated for their ability to inhibit the growth of B16 melanoma cells with the most potent and selective HDAC6I being found to decrease tumor cell growth. To the best of our knowledge, this work constitutes the first report of HDAC6-selective inhibitors that possess antiproliferative effects against melanoma cells.

  DOI：

  10.1021/jm301098e
• 作为产物：
  描述：

  色胺盐酸盐 、 对甲酰基苯甲酸甲酯 在 甲醇 、 三乙胺 、 三乙酰氧基硼氢化钠 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 4.0h， 以48%的产率得到methyl 4-(((2-(1H-indol-3-yl)ethyl)amino)methyl)benzoate
  参考文献：
  名称：

  [EN] ACYLUREA CONNECTED AND SULFONYLUREA CONNECTED HYDROXAMATES
  [FR] HYDROXAMATES CONNECTES A L'ACYLUREE ET A LA SULFONYLUREE

  摘要：

  本发明涉及羟肟酸酯化合物，这些化合物是组蛋白去乙酰化酶的抑制剂。更具体地，本发明涉及含有酰脲/磺酰脲的化合物及其制备方法。这些化合物可能作为治疗增殖性疾病以及涉及、与组蛋白去乙酰化酶活性有关的其他疾病的药物而有用。

  公开号：

  WO2005040101A1

文献信息

• [EN] SELECTIVE HISTONE DEACTYLASE 6 INHIBITORS<br/>[FR] INHIBITEURS SÉLECTIFS D'HISTONE DÉSACÉTYLASE 6
  申请人：H LEE MOFFITT CANCER CT & RES

  公开号：WO2013134467A1

  公开（公告）日：2013-09-12

  Disclosed are selective histone deactylase inhibitors (HDACi) that having Formula (I). Methods of making and using these inhibitors for the treatment of cancer, in particular melanoma are also disclosed.

  披露了具有化学式（I）的选择性组蛋白去乙酰化酶抑制剂（HDACi）。还披露了制备和使用这些抑制剂用于治疗癌症，特别是黑色素瘤的方法。
• Synthesis and cancer antiproliferative activity of new histone deacetylase inhibitors: hydrophilic hydroxamates and 2-aminobenzamide-containing derivatives
  作者：Y. Nagaoka、T. Maeda、Y. Kawai、D. Nakashima、T. Oikawa、K. Shimoke、T. Ikeuchi、H. Kuwajima、S. Uesato

  DOI：10.1016/j.ejmech.2006.02.002

  日期：2006.6

  New series histone deacetylase inhibitors comprising a hydroxamic acid or 2-aminobenzamide group as a zinc-chelating function were synthesized and evaluated for antiproliferative activities against a panel of human cancer cells. The 2-aminobenzamide series inhibitors generally had the potency in cell growth inhibitions comparable to that of MS-275. Among them, the compound having a (3,4-difluorobe

  合成了包含异羟肟酸或2-氨基苯甲酰胺基团作为锌螯合功能的新系列组蛋白脱乙酰酶抑制剂，并评估了其对一组人类癌细胞的抗增殖活性。2-氨基苯甲酰胺系列抑制剂通常具有与MS-275相当的对细胞生长的抑制作用。其中，在分子的一端具有（3,4-二氟苄基）（2-羟乙基）氨基，另一侧具有2-氨基苯甲酰胺基的化合物显示出作为抗癌候选药物最有前景的特征。与MS-275对正常成纤维细胞CCD-1059SK相比毒性较低。另外，该衍生物在人血浆稳定性测试中显示出高回收率。
• Acylurea Connected And Sulfonylurea Connected Hydroxamates
  申请人：Lim Ze-Yi

  公开号：US20080070954A1

  公开（公告）日：2008-03-20

  The present invention relates to hydroxamate compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to acylurea/sulfonylurea containing compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with enzymes having histone deacetylase activities.

  本发明涉及羟酰胺化合物，其为组蛋白去乙酰化酶的抑制剂。更具体地说，本发明涉及含有酰基脲/磺酰基脲的化合物及其制备方法。这些化合物可能作为药物用于治疗增殖性疾病以及其他涉及或与具有组蛋白去乙酰化酶活性的酶相关的疾病。
• SELECTIVE HISTONE DEACTYLASE 6 INHIBITORS
  申请人：H.LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

  公开号：US20150056213A1

  公开（公告）日：2015-02-26

  Disclosed are selective histone deactylase inhibitors (HDACi) that having Formula (I). Methods of making and using these inhibitors for the treatment of cancer, in particular melanoma are also disclosed.

  本发明涉及具有式(I)的选择性组蛋白去乙酰化酶抑制剂（HDACi）。本发明还公开了制备和使用这些抑制剂治疗癌症，特别是黑色素瘤的方法。
• Selective histone deactylase 6 inhibitors
  申请人：H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

  公开号：US10227295B2

  公开（公告）日：2019-03-12

  Disclosed are selective histone deactylase inhibitors (HDACi) that having Formula I. Methods of making and using these inhibitors for the treatment of cancer, in particular melanoma are also disclosed.

  所公开的是具有式 I 的选择性组蛋白去乙酰化酶抑制剂（HDACi）。还公开了制造和使用这些抑制剂治疗癌症，特别是黑色素瘤的方法。