3-(2-chloroacetyl)-2-butyl-1,3-diazaspiro[4,4]non-1-en-4-one | 1253107-79-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-(2-chloroacetyl)-2-butyl-1,3-diazaspiro[4,4]non-1-en-4-one
• 英文别名: 2-Butyl-3-(2-chloroacetyl)-1,3-diazaspiro[4.4]non-1-en-4-one
• CAS: 1253107-79-7
• 化学式: C₁₃H₁₉ClN₂O₂
• 分子量: 270.759
• InChiKey: GIHLDSGUWVSHRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  49.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (Z)-5-(4-hydroxyphenylmethylene)-2,4-thiazolidinedione 、 3-(2-chloroacetyl)-2-butyl-1,3-diazaspiro[4,4]non-1-en-4-one 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以97%的产率得到5-[4-[2-(2-butyl-4-oxo-1,3-diazaspiro[4,4]non-1-en-3-yl)-2-oxoethoxy]benzylidene]thiazolidine-2,4-dione
  参考文献：
  名称：

  Synthesis and primary cytotoxicity evaluation of new 5-benzylidene-2,4-thiazolidinedione derivatives

  摘要：

  In the present work, ten novel derivatives (3a-3j) of 5-benzylidene-2,4-thiazolidinediones were synthesized and their structures were determined by analytical and spectral (FTIR, (1)H NMR, (13)C NMR) methods. The newly synthesized compounds were evaluated for their antiproliferative activity at Tata Memorial's Advanced Center for Treatment. Research and Education in Cancer (ACTREC), India, in a panel of 7 cancer cell lines using four concentrations at 10-fold dilutions. Sulforhodamine B (SRB) protein assay was used to estimate cell stability or growth. Though the compounds showed varying degrees of cytotoxicity in the tested cell lines, most marked effect was observed by compound 3e in MCF7 (breast cancer), K562 (leukemia) and GURAV (nasopharyngeal cancer) cell lines with logo GI(50) values of -6 7. -6.72 and -6.73 respectively. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.07.014
• 作为产物：
  描述：

  氯乙酰氯 、 2-丁基-1,3-二氮杂螺环-[4,4]壬-1-烯-4酮 在 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 生成 3-(2-chloroacetyl)-2-butyl-1,3-diazaspiro[4,4]non-1-en-4-one
  参考文献：
  名称：

  亚苄基噻唑烷二酮：与伊马替尼联合使用时的合成，抗增殖机制的体外研究以及体内功效的确定。

  摘要：

  噻唑烷二酮（TZD）由于其已被证实的抗糖尿病活性和令人鼓舞的抗癌药物发现而成为令人关注的支架。我们合成了亚苄基噻唑烷二酮衍生物，该衍生物在慢性髓样白血病细胞K562中表现出优异的抗增殖作用，活性最高的化合物3t和3x的GI 50值分别为0.9和0.23 µM。发现这两种化合物都以时间和剂量依赖性的方式阻止了K562细胞在G0 / G1期的生长。此外，western blot分析显示3t和3x还可抑制细胞增殖标志物，PCNA和Cyclin D1的表达，以及化合物3x上调凋亡标志物，裂解PARP1和激活的胱天蛋白酶3，这可能是优异的抗增殖作用的可能机制。这些化合物表现出的效果。3t和3x与伊马替尼的体外联合研究发现可增强伊马替尼的抗肿瘤作用。进一步体内与单独使用伊马替尼或经测试化合物处理的动物相比，单独使用3t和3x并与伊马替尼联合使用的K562异种移植物的疗效被证明是有前途的，远胜于对照组，

  DOI：

  10.1016/j.bmcl.2020.127561

文献信息

• Synthesis and primary cytotoxicity evaluation of new 5-benzylidene-2,4-thiazolidinedione derivatives
  作者：Vijay Patil、Kalpana Tilekar、Sonali Mehendale-Munj、Rhea Mohan、C.S. Ramaa

  DOI：10.1016/j.ejmech.2010.07.014

  日期：2010.10

  In the present work, ten novel derivatives (3a-3j) of 5-benzylidene-2,4-thiazolidinediones were synthesized and their structures were determined by analytical and spectral (FTIR, (1)H NMR, (13)C NMR) methods. The newly synthesized compounds were evaluated for their antiproliferative activity at Tata Memorial's Advanced Center for Treatment. Research and Education in Cancer (ACTREC), India, in a panel of 7 cancer cell lines using four concentrations at 10-fold dilutions. Sulforhodamine B (SRB) protein assay was used to estimate cell stability or growth. Though the compounds showed varying degrees of cytotoxicity in the tested cell lines, most marked effect was observed by compound 3e in MCF7 (breast cancer), K562 (leukemia) and GURAV (nasopharyngeal cancer) cell lines with logo GI(50) values of -6 7. -6.72 and -6.73 respectively. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Benzylidene thiazolidinediones: Synthesis, in vitro investigations of antiproliferative mechanisms and in vivo efficacy determination in combination with Imatinib
  作者：Hardik Joshi、Vijay Patil、Kalpana Tilekar、Neha Upadhyay、Vikram Gota、C.S. Ramaa

  DOI：10.1016/j.bmcl.2020.127561

  日期：2020.12

  up-regulated apoptosis markers, cleaved PARP1 and activated caspase 3, which could be a possible mechanism for the excellent antiproliferative effects exhibited by these compounds. In vitro combination studies of 3t and 3x with Imatinib found to potentiate the antitumor effects of Imatinib. Further in vivo efficacy in K562 xenografts, of 3t and 3x alone and in combination with Imatinib was found to be

  噻唑烷二酮（TZD）由于其已被证实的抗糖尿病活性和令人鼓舞的抗癌药物发现而成为令人关注的支架。我们合成了亚苄基噻唑烷二酮衍生物，该衍生物在慢性髓样白血病细胞K562中表现出优异的抗增殖作用，活性最高的化合物3t和3x的GI 50值分别为0.9和0.23 µM。发现这两种化合物都以时间和剂量依赖性的方式阻止了K562细胞在G0 / G1期的生长。此外，western blot分析显示3t和3x还可抑制细胞增殖标志物，PCNA和Cyclin D1的表达，以及化合物3x上调凋亡标志物，裂解PARP1和激活的胱天蛋白酶3，这可能是优异的抗增殖作用的可能机制。这些化合物表现出的效果。3t和3x与伊马替尼的体外联合研究发现可增强伊马替尼的抗肿瘤作用。进一步体内与单独使用伊马替尼或经测试化合物处理的动物相比，单独使用3t和3x并与伊马替尼联合使用的K562异种移植物的疗效被证明是有前途的，远胜于对照组，