10-(3-chlorobenzyl)-N-(3-(cyclohexyl(methyl)amino)-propyl)-11-oxo-10,11 dihydrodibenzo[b,f][1,4]thiazepine-8-carboxamide | 1319194-05-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: 10-(3-chlorobenzyl)-N-(3-(cyclohexyl(methyl)amino)-propyl)-11-oxo-10,11 dihydrodibenzo[b,f][1,4]thiazepine-8-carboxamide
• 英文别名: 5-[(3-chlorophenyl)methyl]-N-[3-[cyclohexyl(methyl)amino]propyl]-6-oxobenzo[b][1,4]benzothiazepine-3-carboxamide
• CAS: 1319194-05-2
• 化学式: C₃₁H₃₄ClN₃O₂S
• 分子量: 548.149
• InChiKey: RQRVPWMXIXVSBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  78
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  10-(3-chlorobenzyl)-N-(3-(cyclohexyl(methyl)amino)-propyl)-11-oxo-10,11 dihydrodibenzo[b,f][1,4]thiazepine-8-carboxamide 在 碳酸氢钠 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以65%的产率得到N-[3-(cyclohexylmethylamino)propyl]-10-[(3-chloro-phenyl)methyl]-10,11-dihydro-11-oxo-dibenzo-[b,f][1,4]-thiazepine-8-carboxamide-5-oxide
  参考文献：
  名称：

  Evaluation of NTF1836 as an inhibitor of the mycothiol biosynthetic enzyme MshC in growing and non-replicating Mycobacterium tuberculosis

  摘要：

  The mycothiol biosynthesis enzyme MshC catalyzes the ligation of cysteine with the pseudodisaccharide GlcN-Ins and has been identified as an essential enzyme in Mycobacterium tuberculosis. We now report on the development of NTF1836 as a micromolar inhibitor of MshC. Using commercial libraries, we conducted preliminary structure-activity relationship (SAR) studies on NTF1836. Based on this data, NTF1836 and five structurally related compounds showed similar activity towards clinical strains of M. tuberculosis. A gram scale synthesis was developed to provide ample material for biological studies. Using this material, we determined that inhibition of M. tuberculosis growth by NTF1836 was accompanied by a fall in mycothiol and an increase in GlcN-Ins consistent with the targeting of MshC. We also determined that NTF1836 kills non-replicating M. tuberculosis in the carbon starvation model of latency. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.05.028
• 作为产物：
  描述：

  methyl 11-oxo-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxylate 在 sodium hydride 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 74.5h， 生成 10-(3-chlorobenzyl)-N-(3-(cyclohexyl(methyl)amino)-propyl)-11-oxo-10,11 dihydrodibenzo[b,f][1,4]thiazepine-8-carboxamide
  参考文献：
  名称：

  Evaluation of NTF1836 as an inhibitor of the mycothiol biosynthetic enzyme MshC in growing and non-replicating Mycobacterium tuberculosis

  摘要：

  The mycothiol biosynthesis enzyme MshC catalyzes the ligation of cysteine with the pseudodisaccharide GlcN-Ins and has been identified as an essential enzyme in Mycobacterium tuberculosis. We now report on the development of NTF1836 as a micromolar inhibitor of MshC. Using commercial libraries, we conducted preliminary structure-activity relationship (SAR) studies on NTF1836. Based on this data, NTF1836 and five structurally related compounds showed similar activity towards clinical strains of M. tuberculosis. A gram scale synthesis was developed to provide ample material for biological studies. Using this material, we determined that inhibition of M. tuberculosis growth by NTF1836 was accompanied by a fall in mycothiol and an increase in GlcN-Ins consistent with the targeting of MshC. We also determined that NTF1836 kills non-replicating M. tuberculosis in the carbon starvation model of latency. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.05.028