tert-butyl 8-fluoro-5-methyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate | 870471-45-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: tert-butyl 8-fluoro-5-methyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate
• 英文别名: 8-fluoro-5-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester；8-Fluoro-5-methyl-1,3,4,5-tetrahydro-pyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester；tert-butyl 8-fluoro-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2-carboxylate
• CAS: 870471-45-7
• 化学式: C₁₇H₂₁FN₂O₂
• 分子量: 304.364
• InChiKey: BAMITVKGYOPSQX-UHFFFAOYSA-N

物化性质

• 沸点：
  440.4±45.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  34.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 8-fluoro-5-methyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate 在 盐酸 、 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-) 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (1R,2R)-N-(1-cyanocyclopropyl)-2-[(8-fluoro-5-methyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxamide
  参考文献：
  名称：

  (1R,2R)-N-(1-Cyanocyclopropyl)-2-(6-methoxy-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxamide (AZD4996): A Potent and Highly Selective Cathepsin K Inhibitor for the Treatment of Osteoarthritis

  摘要：

  Directed screening of nitrile compounds revealed 3 as a highly potent cathepsin K inhibitor but with cathepsin S activity and very poor stability to microsomes. Synthesis of compounds with reduced molecular complexity, such as 7, revealed key SAR and demonstrated that baseline physical properties and in vitro stability were in fact excellent for this series. The tricycle carboline P3 unit was discovered by hypothesis-based design using existing structural information. Optimization using small substituents, knowledge from matched molecular pairs, and control of lipophilicity yielded compounds very close to the desired profile, of which 34 (AZD4996) was selected on the basis of pharmacokinetic profile.

  DOI：

  10.1021/jm3007257
• 作为产物：
  描述：

  8-氟-2,3,4,5-四氢-1H-吡啶并[4,3-b]吲哚 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.33h， 生成 tert-butyl 8-fluoro-5-methyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate
  参考文献：
  名称：

  [EN] 1, 3, 4, 5-TETRAHYDRO-2H-PYRIDO[4,3-B]INDOLE DERIVATIVES FOR THE TREATMENT, ALLEVIATION OR PREVENTION OF DISORDERS ASSOCIATED WITH TAU AGGREGATES LIKE ALZHEIMER'S DISEASE
  [FR] DÉRIVÉS DE 1,3,4,5-TÉTRAHYDRO-2H-PYRIDO[4,3-B]INDOLE POUR LE TRAITEMENT, LE SOULAGEMENT OU LA PRÉVENTION DE TROUBLES ASSOCIÉS À DES AGRÉGATS DE TAU COMME LA MALADIE D'ALZHEIMER

  摘要：

  本发明涉及一类新化合物，可用于治疗、缓解或预防与Tau蛋白聚集相关的一组疾病和异常，包括但不限于神经原纤维缠结（NFTs），如阿尔茨海默病（AD）。

  公开号：

  WO2019134978A1

文献信息

• Tetrahydrocarboline antiviral agents
  申请人：Ruediger H. Edward

  公开号：US20050267130A1

  公开（公告）日：2005-12-01

  The invention encompasses a series of tetrahydrocarboline compounds of Formula I which inhibit HIV entry by attaching to the exterior viral envelop protein gp120 and interrupting the viral entry process, possibly by interfering with the cellular receptor CD4. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV.

  该发明涵盖了一系列的四氢喹啉化合物，其化学式为I，通过与病毒外包膜蛋白gp120结合并干扰病毒进入过程来抑制HIV进入，可能是通过干扰细胞受体CD4来实现的。这种作用使得这些化合物在治疗HIV感染和艾滋病方面非常有用。该发明还涵盖了用于治疗HIV感染者的药物组合物和方法。
• Compounds for the treatment, alleviation or prevention of disorders associated with Tau aggregates
  申请人：AC Immune SA

  公开号：US10633383B2

  公开（公告）日：2020-04-28

  The present invention relates to novel compounds that can be employed in the treatment, alleviation or prevention of a group of disorders and abnormalities associated with Tau (Tubulin associated unit) protein aggregates including, but not limited to, Neurofibrillary Tangles (NFTs), such as Alzheimer's disease (AD).

  本发明涉及新型化合物，可用于治疗、缓解或预防与 Tau（微管蛋白相关单位）蛋白聚集有关的一组疾病和异常，包括但不限于神经纤维缠结（NFT），如阿尔茨海默病（AD）。
• Novel compounds for the treatment, alleviation or prevention of disorders associated with Tau aggregates
  申请人：AC Immune SA

  公开号：US20190211012A1

  公开（公告）日：2019-07-11

  The present invention relates to novel compounds that can be employed in the treatment, alleviation or prevention of a group of disorders and abnormalities associated with Tau (Tubulin associated unit) protein aggregates including, but not limited to, Neurofibrillary Tangles (NFTs), such as Alzheimer's disease (AD).
• US7449476B2
  申请人：——

  公开号：US7449476B2

  公开（公告）日：2008-11-11