4-(1-(2,3-dihydrobenzo[b][1,4]dioxin-6-ylsulfonyl)-1H-indol-3-yl)pyrimidin-2-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 4-(1-(2,3-dihydrobenzo[b][1,4]dioxin-6-ylsulfonyl)-1H-indol-3-yl)pyrimidin-2-amine
• 英文别名: 4-[1-(2,3-Dihydro-1,4-benzodioxin-6-ylsulfonyl)indol-3-yl]pyrimidin-2-amine；4-[1-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)indol-3-yl]pyrimidin-2-amine
• 化学式: C₂₀H₁₆N₄O₄S
• 分子量: 408.437
• InChiKey: CJSZWTVTAXPDPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1H-吲哚,3-乙酰基-1-[(4-甲基苯基)磺酰]- 在 4-二甲氨基吡啶 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙二醇甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 4-(1-(2,3-dihydrobenzo[b][1,4]dioxin-6-ylsulfonyl)-1H-indol-3-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Meridianin derivatives as potent Dyrk1A inhibitors and neuroprotective agents

  摘要：

  Meridianins are a group of marine-derived indole alkaloids which are reported to possess kinase inhibitory activities. In the present Letter, we report synthesis of N1-substituted and C-ring modified meridianin derivatives and their evaluation as Dyrk1A inhibitors and neuroprotective agents. Among the library of 52 compounds screened, morpholinoyl linked derivative 26b and 2-nitro-4-trifluoromethyl phenyl sulfonyl derivative 29v displayed potent inhibition of Dyrk1A with IC50 values of 0.5 and 0.53 mu M, respectively. The derivative 26b also inhibited Dyrk2 and Dyrk3 with IC50 values of 1.4 and 2.2 mu M, respectively showing 2.2 and 4.4 fold selectivity for Dyrk1A with respect to Dyrk2 and Dyrk3. The compound 26b was not cytotoxic to human neuroblastoma SH-SY5Y cells (IC50 > 100 mu M) and it displayed significant neuroprotection against glutamate-induced neurotoxicity in these cells at 10 mu M. Molecular modelling studies of compound 26b led to identification of key interactions in the binding site of Dyrk1A and the possible reasons for observed Dyrk1A selectivity over Dyrk2. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.05.034

文献信息

• Synthesis, antimalarial and antitubercular activities of meridianin derivatives
  作者：Rammohan R. Yadav、Shabana I. Khan、Samsher Singh、Inshad A. Khan、Ram A. Vishwakarma、Sandip B. Bharate

  DOI：10.1016/j.ejmech.2015.05.020

  日期：2015.6

  Meridianins are marine-derived indole alkaloids, known to possess kinase inhibitory and antimalarial activities. A series of N-aryl and heteroaryl sulfonamide derivatives of meridianins were prepared and screened for antimalarial activity against D6 and W2 strains of Plasmodium falciparum. 2-Nitro-4-trifluoromethyl sulfonamide derivative 14v displayed promising antiplasmodial activity against both strains with IC50 values of 2.56 and 3.41 mu M, respectively. These compounds were not cytotoxic to mammalian cell lines including VERO (monkey kidney fibroblasts), LLC-PK1 (pig kidney epithelial cells) and four cancer cell lines; SK-MEL (human malignant, melanoma), KB (human epidermal carcinoma), BT-549 (ductal carcinoma), SK-OV-3 (human ovary carcinoma) up to 25 mu g/ml. Furthermore, all sulfonamide derivatives along with acyl, alkyl and C-ring modified derivatives of meridianins were screened for antitubercular activity against a sensitive strain (H(37)Rv) of Mycobacterium tuberculosis (Mtb), wherein several compounds showed MIC values in the range of 5.2-304.8 mu M. Meridianin C (3) and meridianin G (7) showed anti-tubercular activity with MIC values of 111.1 and 304.8 mu M, respectively. The C-ring modified analog 12 exhibited potent anti-tubercular activity against H(37)Rv strain of Mtb with MIC of 5.2 mu M. Furthermore, the most potent analogs 11b and 12 were screened against two clinical isolates of M. tuberculosis INHR and MDR and one laboratory generated mutant strain Rif(R). These two analogs 11b and 12 displayed promising activity against these resistant strains with MIC values in the range of 5.2 -187.7 mu M. This is the first report on the anti-tubercular activity of this scaffold. (C) 2015 Published by Elsevier Masson SAS.
• Meridianin derivatives as potent Dyrk1A inhibitors and neuroprotective agents
  作者：Rammohan R. Yadav、Sadhana Sharma、Prashant Joshi、Abubakar Wani、Ram A. Vishwakarma、Ajay Kumar、Sandip B. Bharate

  DOI：10.1016/j.bmcl.2015.05.034

  日期：2015.8

  Meridianins are a group of marine-derived indole alkaloids which are reported to possess kinase inhibitory activities. In the present Letter, we report synthesis of N1-substituted and C-ring modified meridianin derivatives and their evaluation as Dyrk1A inhibitors and neuroprotective agents. Among the library of 52 compounds screened, morpholinoyl linked derivative 26b and 2-nitro-4-trifluoromethyl phenyl sulfonyl derivative 29v displayed potent inhibition of Dyrk1A with IC50 values of 0.5 and 0.53 mu M, respectively. The derivative 26b also inhibited Dyrk2 and Dyrk3 with IC50 values of 1.4 and 2.2 mu M, respectively showing 2.2 and 4.4 fold selectivity for Dyrk1A with respect to Dyrk2 and Dyrk3. The compound 26b was not cytotoxic to human neuroblastoma SH-SY5Y cells (IC50 > 100 mu M) and it displayed significant neuroprotection against glutamate-induced neurotoxicity in these cells at 10 mu M. Molecular modelling studies of compound 26b led to identification of key interactions in the binding site of Dyrk1A and the possible reasons for observed Dyrk1A selectivity over Dyrk2. (C) 2015 Elsevier Ltd. All rights reserved.