2-benzyl-6-(4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde | 1176457-05-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-benzyl-6-(4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde
• CAS: 1176457-05-8
• 化学式: C₁₉H₁₅N₃O₂S
• 分子量: 349.413
• InChiKey: JKJDQOLTPXNIEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  84.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-吲哚酮 、 2-benzyl-6-(4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde 在 哌啶 作用下， 以 甲醇 为溶剂， 以79%的产率得到3-((2-benzyl-6-(4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl)methylidene)-1,3-dihydro-2H-indol-2-one
  参考文献：
  名称：

  Identification of a novel BCL2-specific inhibitor that binds predominantly to the BH1 domain

  摘要：

  The antiapoptotic protein BCL2 is overexpressed in several cancers and contributes to prolonged cell survival and chemoresistance, lending itself as an excellent target for cancer therapy. Here, we report the design, synthesis, and characterization of Disarib, a novel BCL2 inhibitor. Disarib showed selective cytotoxicity in BCL2 high cancer cell lines, and CLL patient primary cells, as compared to BCL2 low cell lines. BCL2 knockdown in cells rendered remarkable resistance to Disarib, while sensitivity was regained upon its ectopic expression, establishing target specificity. In silico, biochemical and biophysical studies demonstrated strong affinity of Disarib to BCL2, but not to other antiapoptotic BCL2 family members viz., BCL‐xL, BCL2A1 etc. Interestingly, biophysical studies showed that BH1 domain deletion mutant demonstrated ~ 67‐fold reduction in BCL2‐Disarib interaction, while it was only ~ 20‐fold in the case of BH3 deletion mutant, suggesting predominant involvement of the BH1 domain for Disarib binding. Thus, we report identification of a novel BCL2 inhibitor with a unique mechanism of BCL2 inhibition, as opposed to the well‐studied BH3 domain targeting.

  DOI：

  10.1111/febs.13815
• 作为产物：
  描述：

  5-苄基-[1,3,4]噁二唑-2-胺 在 sodium carbonate 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 2-benzyl-6-(4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde
  参考文献：
  名称：

  Synthesis, Hypoglycaemic, Hypolipidemic and PPARγ Agonist Activities of 5-(2-Alkyl/aryl-6-Arylimidazo[2,1-b][1,3,4]thiadiazol-5-yl)methylene-1,3-Thiazolidinediones

  摘要：

  A novel series of 5‐(2‐alkyl/aryl‐6‐arylimidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)methylene‐1,3‐thiazolidinediones were synthesized as possible PPARγ agonists. The structures of these target molecules were established by spectral and analytical data. All the newly synthesized compounds were screened for their in vivo hypoglycaemic and hypolipidemic activity in male Wistar rats. Further, compounds with good activity were screened for PPARγ agonist activity. Among the screened compounds, 5‐{[2‐Cyclohexyl‐6‐(4‐methoxyphenyl)imidazo[2,1‐b] [1,3,4]thiadiazol‐5‐yl]methylene}‐1,3‐thiazolidine‐2,4‐dione (3i) exhibits promising hypoglycaemic and hypolipidemic activity via potential PPARγ agonist activity.

  DOI：

  10.1111/cbdd.12140

文献信息

• Kumar, Sujeet; Metikurki, Basavaraj; Bhadauria, Vivek Singh, Acta poloniae pharmaceutica, 2016, vol. 73, # 4, p. 913 - 929
  作者：Kumar, Sujeet、Metikurki, Basavaraj、Bhadauria, Vivek Singh、De Clercq, Erik、Schols, Dominique、Tokuda, Harukuni、Karki, Subhas S.

  DOI：——

  日期：——
• Identification of a novel BCL2-specific inhibitor that binds predominantly to the BH1 domain
  作者：Divyaanka Iyer、Supriya V. Vartak、Archita Mishra、Gunaseelan Goldsmith、Sujeet Kumar、Mrinal Srivastava、Mahesh Hegde、Vidya Gopalakrishnan、Mark Glenn、Mahesh Velusamy、Bibha Choudhary、Nagesh Kalakonda、Subhas S. Karki、Avadhesha Surolia、Sathees C. Raghavan

  DOI：10.1111/febs.13815

  日期：2016.9

  The antiapoptotic protein BCL2 is overexpressed in several cancers and contributes to prolonged cell survival and chemoresistance, lending itself as an excellent target for cancer therapy. Here, we report the design, synthesis, and characterization of Disarib, a novel BCL2 inhibitor. Disarib showed selective cytotoxicity in BCL2 high cancer cell lines, and CLL patient primary cells, as compared to BCL2 low cell lines. BCL2 knockdown in cells rendered remarkable resistance to Disarib, while sensitivity was regained upon its ectopic expression, establishing target specificity. In silico, biochemical and biophysical studies demonstrated strong affinity of Disarib to BCL2, but not to other antiapoptotic BCL2 family members viz., BCL‐xL, BCL2A1 etc. Interestingly, biophysical studies showed that BH1 domain deletion mutant demonstrated ~ 67‐fold reduction in BCL2‐Disarib interaction, while it was only ~ 20‐fold in the case of BH3 deletion mutant, suggesting predominant involvement of the BH1 domain for Disarib binding. Thus, we report identification of a novel BCL2 inhibitor with a unique mechanism of BCL2 inhibition, as opposed to the well‐studied BH3 domain targeting.
• Synthesis, Hypoglycaemic, Hypolipidemic and PPARγ Agonist Activities of 5-(2-Alkyl/aryl-6-Arylimidazo[2,1-b][1,3,4]thiadiazol-5-yl)methylene-1,3-Thiazolidinediones
  作者：Mohammed Iqbal A. Khazi、Ningaraddi S. Belavagi、Kwang R. Kim、Young-Dae Gong、Imtiyaz Ahmed M. Khazi

  DOI：10.1111/cbdd.12140

  日期：2013.8

  A novel series of 5‐(2‐alkyl/aryl‐6‐arylimidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)methylene‐1,3‐thiazolidinediones were synthesized as possible PPARγ agonists. The structures of these target molecules were established by spectral and analytical data. All the newly synthesized compounds were screened for their in vivo hypoglycaemic and hypolipidemic activity in male Wistar rats. Further, compounds with good activity were screened for PPARγ agonist activity. Among the screened compounds, 5‐[2‐Cyclohexyl‐6‐(4‐methoxyphenyl)imidazo[2,1‐b] [1,3,4]thiadiazol‐5‐yl]methylene}‐1,3‐thiazolidine‐2,4‐dione (3i) exhibits promising hypoglycaemic and hypolipidemic activity via potential PPARγ agonist activity.