9-iodo-4-dedimethylaminodoxycycline | 731024-25-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 四环素类
• 英文名称: 9-iodo-4-dedimethylaminodoxycycline
• CAS: 731024-25-2
• 化学式: C₂₀H₁₈INO₈
• 分子量: 527.269
• InChiKey: UEFJLRULJCRBSA-MGUFRBGMSA-N

物化性质

• 沸点：
  747.5±60.0 °C(Predicted)
• 密度：
  2.09±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.72
• 重原子数：
  30.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  178.38
• 氢给体数：
  6.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  9-iodo-4-dedimethylaminodoxycycline 在 甲醇 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 水 、 三乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成
  参考文献：
  名称：

  C9‐Functionalized Doxycycline Analogs as Drug Candidates to Prevent Pathological α‐Synuclein Aggregation and Neuroinflammation in Parkinson's Disease Degeneration

  摘要：

  Doxycycline, a semi‐synthetic tetracycline, is a widely used antibiotic for treating mild‐to‐moderate infections, including skin problems. However, its anti‐inflammatory and antioxidant properties, combined with its ability to interfere with α‐synuclein aggregation, make it an attractive candidate for repositioning in Parkinson's disease. Nevertheless, the antibiotic activity of doxycycline restricts its potential use for long‐term treatment of Parkinsonian patients. In the search for non‐antibiotic tetracyclines that could operate against Parkinson's disease pathomechanisms, eighteen novel doxycycline derivatives were designed. Specifically, the dimethyl‐amino group at C4 was reduced, resulting in limited antimicrobial activity, and several coupling reactions were performed at position C9 of the aromatic D ring, this position being one of the most reactive for introducing substituents. Using the Thioflavin‐T assay, we found seven compounds were more effective than doxycycline in inhibiting α‐synuclein aggregation. Furthermore, two of these derivatives exhibited better anti‐inflammatory effects than doxycycline in a culture system of microglial cells used to model Parkinson's disease neuroinflammatory processes. Overall, through structure‐activity relationship studies, we identified two newly designed tetracyclines as promising drug candidates for Parkinson's disease treatment.

  DOI：

  10.1002/cmdc.202300597
• 作为产物：
  描述：

  强力霉素 在 N-碘代丁二酰亚胺 、 溶剂黄146 、 三氟乙酸 、 锌 作用下， 以 四氢呋喃 为溶剂， 反应 27.0h， 生成 9-iodo-4-dedimethylaminodoxycycline
  参考文献：
  名称：

  C9‐Functionalized Doxycycline Analogs as Drug Candidates to Prevent Pathological α‐Synuclein Aggregation and Neuroinflammation in Parkinson's Disease Degeneration

  摘要：

  Doxycycline, a semi‐synthetic tetracycline, is a widely used antibiotic for treating mild‐to‐moderate infections, including skin problems. However, its anti‐inflammatory and antioxidant properties, combined with its ability to interfere with α‐synuclein aggregation, make it an attractive candidate for repositioning in Parkinson's disease. Nevertheless, the antibiotic activity of doxycycline restricts its potential use for long‐term treatment of Parkinsonian patients. In the search for non‐antibiotic tetracyclines that could operate against Parkinson's disease pathomechanisms, eighteen novel doxycycline derivatives were designed. Specifically, the dimethyl‐amino group at C4 was reduced, resulting in limited antimicrobial activity, and several coupling reactions were performed at position C9 of the aromatic D ring, this position being one of the most reactive for introducing substituents. Using the Thioflavin‐T assay, we found seven compounds were more effective than doxycycline in inhibiting α‐synuclein aggregation. Furthermore, two of these derivatives exhibited better anti‐inflammatory effects than doxycycline in a culture system of microglial cells used to model Parkinson's disease neuroinflammatory processes. Overall, through structure‐activity relationship studies, we identified two newly designed tetracyclines as promising drug candidates for Parkinson's disease treatment.

  DOI：

  10.1002/cmdc.202300597

文献信息

• Substituted Tetracycline Compounds
  申请人：Kim Oak K.

  公开号：US20100305072A1

  公开（公告）日：2010-12-02

  The present invention pertains, at least in part, to novel substituted tetracycline compounds. These tetracycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms.

  本发明至少部分涉及新型替代四环素化合物。这些四环素化合物可用于治疗许多对四环素化合物敏感的疾病状态，如细菌感染和肿瘤。
• TETRACYCLINE COMPOUNDS HAVING TARGET THERAPEUTIC ACTIVITIES
  申请人：Paratek Pharmaceuticals, Inc.

  公开号：US20180016225A1

  公开（公告）日：2018-01-18

  Methods and compounds for treating diseases with tetracycline compounds having a target therapeutic activity are described.

  使用具有目标治疗活性的四环素化合物治疗疾病的方法和化合物被描述。
• US9278911B2
  申请人：——

  公开号：US9278911B2

  公开（公告）日：2016-03-08