5-chloro-3-(piperidin-4-yl)indolin-2-one | 1368792-02-2

• 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: 5-chloro-3-(piperidin-4-yl)indolin-2-one
• 英文别名: 5-Chloro-3-piperidin-4-yl-1,3-dihydroindol-2-one
• CAS: 1368792-02-2
• 化学式: C₁₃H₁₅ClN₂O
• 分子量: 250.728
• InChiKey: OFGKPXPWCJBPSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl methanesulfonate 、 5-chloro-3-(piperidin-4-yl)indolin-2-one 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以38.6%的产率得到1-(2-(4-(5-chloro-2-oxoindolin-3-yl)piperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one
  参考文献：
  名称：

  Benzimidazoles: Novel Mycobacterial Gyrase Inhibitors from Scaffold Morphing

  摘要：

  Type II topoisomerases are well conserved across the bacterial species, and inhibition of DNA gyrase by fluoroquinolones has provided an attractive option for treatment of tuberculosis (TB). However, the emergence of fluoroquinolone-resistant strains of Mycobacterium tuberculosis (Mtb) poses a threat for its sustainability. A scaffold hopping approach using the binding mode of novel bacterial topoisomerase inhibitors (NBTIs) led to the identification of a novel class of benzimidazoles as DNA gyrase inhibitors with potent anti-TB activity. Docking of benzimidazoles to a NBTI bound crystal structure suggested that this class of compound makes key contacts in the enzyme active site similar to the reported NBTIs. This observation was further confirmed through the measurement of DNA gyrase inhibition, and activity against Mtb strains harboring mutations that confer resistance to aminopiperidines based NBTIs and Mtb strains resistant to moxifloxacin. Structure activity relationship modification at the C-7 position of the left-hand side ring provided further avenue to improve hERG selectivity for this chemical series that has been the major challenges for NBTIs.

  DOI：

  10.1021/ml5001728
• 作为产物：
  描述：

  5-氯氧化吲哚 在 盐酸 、 5%-palladium/activated carbon 、 甲酸铵 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 3.5h， 生成 5-chloro-3-(piperidin-4-yl)indolin-2-one
  参考文献：
  名称：

  Benzimidazoles: Novel Mycobacterial Gyrase Inhibitors from Scaffold Morphing

  摘要：

  Type II topoisomerases are well conserved across the bacterial species, and inhibition of DNA gyrase by fluoroquinolones has provided an attractive option for treatment of tuberculosis (TB). However, the emergence of fluoroquinolone-resistant strains of Mycobacterium tuberculosis (Mtb) poses a threat for its sustainability. A scaffold hopping approach using the binding mode of novel bacterial topoisomerase inhibitors (NBTIs) led to the identification of a novel class of benzimidazoles as DNA gyrase inhibitors with potent anti-TB activity. Docking of benzimidazoles to a NBTI bound crystal structure suggested that this class of compound makes key contacts in the enzyme active site similar to the reported NBTIs. This observation was further confirmed through the measurement of DNA gyrase inhibition, and activity against Mtb strains harboring mutations that confer resistance to aminopiperidines based NBTIs and Mtb strains resistant to moxifloxacin. Structure activity relationship modification at the C-7 position of the left-hand side ring provided further avenue to improve hERG selectivity for this chemical series that has been the major challenges for NBTIs.

  DOI：

  10.1021/ml5001728

文献信息

• Compounds having effects on serotonin-related systems
  申请人：ELI LILLY AND COMPANY

  公开号：EP0722941A2

  公开（公告）日：1996-07-24

  A series of hetero-oxy alkanamines are effective pharmaceuticals for the treatment of conditions related to or affected by the reuptake of serotonin and by the serotonin 1A receptor. The compounds are particularly useful for alleviating the symptoms of nicotine and tobacco withdrawal, and for the treatment of depression and other conditions for which serotonin reuptake inhibitors are used.

  一系列杂氧烷胺是治疗与血清素再摄取和血清素 1A 受体有关或受其影响的病症的有效药物。这些化合物尤其适用于缓解尼古丁和烟草戒断症状，以及治疗抑郁症和其他使用血清素再摄取抑制剂的疾病。
• US5576321A
  申请人：——

  公开号：US5576321A

  公开（公告）日：1996-11-19
• US5614523A
  申请人：——

  公开号：US5614523A

  公开（公告）日：1997-03-25
• US5627196A
  申请人：——

  公开号：US5627196A

  公开（公告）日：1997-05-06
• US5741789A
  申请人：——

  公开号：US5741789A

  公开（公告）日：1998-04-21