spiro[2.3'']oxindole-spiro[3.3']-1'-methyl-5'-(2-thienylmethylidene)tetrahydro-4'(1H)-pyridinone-4-(2-thienyl)hexahydro-1H-pyrrolizine

• 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: spiro[2.3'']oxindole-spiro[3.3']-1'-methyl-5'-(2-thienylmethylidene)tetrahydro-4'(1H)-pyridinone-4-(2-thienyl)hexahydro-1H-pyrrolizine
• 化学式: C₂₈H₂₇N₃O₂S₂
• 分子量: 501.673
• InChiKey: HRLIWICWYOLOKI-KGMUTJDBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  35
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  靛红 、 1-methyl-3,5-bis[(E)-(2-thienyl)methylidene]-4-piperidone 、 DL-脯氨酸 以 甲醇 为溶剂， 以90%的产率得到spiro[2.3'']oxindole-spiro[3.3']-1'-methyl-5'-(2-thienylmethylidene)tetrahydro-4'(1H)-pyridinone-4-(2-thienyl)hexahydro-1H-pyrrolizine
  参考文献：
  名称：

  Discovery of Antimycobacterial Spiro-piperidin-4-ones: An Atom Economic, Stereoselective Synthesis, and Biological Intervention

  摘要：

  An atom economic and stereoselective synthesis of several spiro-piperidin-4-ones through 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatin and (alpha-amino acids viz. proline, phenylglycine, and sarcosine to a series of 1-methyl- 3,5-bis [(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones is described. These compounds were evaluated for their in vitro and in vivo activity against Mycobacterium tuberculosis H37Rv (MTB), multidrug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC2). Compound 4-(4-fluorophenyl)-5-phenylpyrrolo(spiro[2.3"]oxindole)spiro[3.3']-1'-methyl-5'-(4-fluorophenylmethylideiie)piperidin-4'-one (4e) was found to be the most active in vitro with a MIC value of 0.07 mu M against MTB and was 5.1 and 67.2 times more potent than isoniazid and ciprofloxacin, respectively. In vivo, compound 4e decreased the bacterial load in lung and spleen tissues with 1.30 and 3.73-log 1.0 protections respectively and was considered to be promising in reducing bacterial count in lung and spleen tissues.

  DOI：

  10.1021/jm800545k

文献信息

• Discovery of Antimycobacterial Spiro-piperidin-4-ones: An Atom Economic, Stereoselective Synthesis, and Biological Intervention
  作者：Raju Ranjith Kumar、Subbu Perumal、Palaniappan Senthilkumar、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1021/jm800545k

  日期：2008.9.25

  An atom economic and stereoselective synthesis of several spiro-piperidin-4-ones through 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatin and (alpha-amino acids viz. proline, phenylglycine, and sarcosine to a series of 1-methyl- 3,5-bis [(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones is described. These compounds were evaluated for their in vitro and in vivo activity against Mycobacterium tuberculosis H37Rv (MTB), multidrug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC2). Compound 4-(4-fluorophenyl)-5-phenylpyrrolo(spiro[2.3"]oxindole)spiro[3.3']-1'-methyl-5'-(4-fluorophenylmethylideiie)piperidin-4'-one (4e) was found to be the most active in vitro with a MIC value of 0.07 mu M against MTB and was 5.1 and 67.2 times more potent than isoniazid and ciprofloxacin, respectively. In vivo, compound 4e decreased the bacterial load in lung and spleen tissues with 1.30 and 3.73-log 1.0 protections respectively and was considered to be promising in reducing bacterial count in lung and spleen tissues.