8-methoxy-5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole | 618910-07-9

• 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: 8-methoxy-5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole
• 英文别名: 8-methoxy-5-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indole
• CAS: 618910-07-9
• 化学式: C₁₃H₁₆N₂O
• mdl: MFCD06662248
• 分子量: 216.283
• InChiKey: MCBYMISJQYDUKV-UHFFFAOYSA-N

物化性质

• 沸点：
  399.9±37.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  26.2
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  1-(3-氯丙氧基)-4-氟苯 、 8-methoxy-5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 在 potassium carbonate 、 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 18.0h， 生成 2-[3-(4-Fluoro-phenoxy)-propyl]-8-methoxy-5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole
  参考文献：
  名称：

  γ-Carbolines: binding at 5-HT5A serotonin receptors

  摘要：

  Screening of various agents resulted in the identification of 5-methyl-1,2,3,4-tetrahydro-gamma-carboline (1; K-i = 5,300 nM) as a compound with modest affinity for mouse 5-HT5A receptors. Structure-affinity studies were conducted resulting in 5-methyl-2-[3-(4-fluorophenoxy)propyl]- 1,2,3,4-tetrahydro-gamma-carboline (17; K-i = 13 nM). Although 17 also binds at 5-HT2 receptors, it serves as a novel lead for the further development of 5-HT5A ligands. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00527-8
• 作为产物：
  描述：

  4-甲氧基苯肼盐酸盐 在 氢氧化钾 、 sodium hydride 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.25h， 生成 8-methoxy-5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole
  参考文献：
  名称：

  γ-Carbolines: binding at 5-HT5A serotonin receptors

  摘要：

  Screening of various agents resulted in the identification of 5-methyl-1,2,3,4-tetrahydro-gamma-carboline (1; K-i = 5,300 nM) as a compound with modest affinity for mouse 5-HT5A receptors. Structure-affinity studies were conducted resulting in 5-methyl-2-[3-(4-fluorophenoxy)propyl]- 1,2,3,4-tetrahydro-gamma-carboline (17; K-i = 13 nM). Although 17 also binds at 5-HT2 receptors, it serves as a novel lead for the further development of 5-HT5A ligands. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00527-8

文献信息

• [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<br/>[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
  申请人：AC IMMUNE SA

  公开号：WO2019134978A1

  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).

  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）。
• 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）。
• Identification, Structure–Activity Relationship, and Biological Characterization of 2,3,4,5-Tetrahydro-1<i>H</i>-pyrido[4,3-<i>b</i>]indoles as a Novel Class of CFTR Potentiators
  作者：Nicoletta Brindani、Ambra Gianotti、Simone Giovani、Francesca Giacomina、Paolo Di Fruscia、Federico Sorana、Sine Mandrup Bertozzi、Giuliana Ottonello、Luca Goldoni、Ilaria Penna、Debora Russo、Maria Summa、Rosalia Bertorelli、Loretta Ferrera、Emanuela Pesce、Elvira Sondo、Luis J. V. Galietta、Tiziano Bandiera、Nicoletta Pedemonte、Fabio Bertozzi

  DOI：10.1021/acs.jmedchem.0c01050

  日期：2020.10.8

  Cystic fibrosis (CF) is a life-threatening autosomal recessive disease, caused by mutations in the CF transmembrane conductance regulator (CFTR) chloride channel. CFTR modulators have been reported to address the basic defects associated with CF-causing mutations, partially restoring the CFTR function in terms of protein processing and/or channel gating. Small-molecule compounds, called potentiators, are known to ameliorate the gating defect. In this study, we describe the identification of the 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole core as a novel chemotype of potentiators. In-depth structure-activity relationship studies led to the discovery of enantiomerically pure 39 endowed with a good efficacy in rescuing the gating defect of F508del- and G551D-CFTR and a promising in vitro druglike profile. The in vivo characterization of gamma-carboline 39 showed considerable exposure levels and good oral bioavailability, with detectable distribution to the lungs after oral administration to rats. Overall, these findings may represent an encouraging starting point to further expand this chemical class, adding a new chemotype to the existing classes of CFTR potentiators.
• 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).
• γ-Carbolines: binding at 5-HT5A serotonin receptors
  作者：Nantaka Khorana、Anil Purohit、Katherine Herrick-Davis、Milt Teitler、Richard A. Glennon

  DOI：10.1016/s0968-0896(02)00527-8

  日期：2003.3

  Screening of various agents resulted in the identification of 5-methyl-1,2,3,4-tetrahydro-gamma-carboline (1; K-i = 5,300 nM) as a compound with modest affinity for mouse 5-HT5A receptors. Structure-affinity studies were conducted resulting in 5-methyl-2-[3-(4-fluorophenoxy)propyl]- 1,2,3,4-tetrahydro-gamma-carboline (17; K-i = 13 nM). Although 17 also binds at 5-HT2 receptors, it serves as a novel lead for the further development of 5-HT5A ligands. (C) 2002 Elsevier Science Ltd. All rights reserved.