8-(trifluoromethoxy)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole | 907566-27-2

• 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-(trifluoromethoxy)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole
• CAS: 907566-27-2
• 化学式: C₁₂H₁₁F₃N₂O
• mdl: MFCD05663534
• 分子量: 256.227
• InChiKey: YMIMDJBSJBNETN-UHFFFAOYSA-N

物化性质

• 沸点：
  344.4±37.0 °C(Predicted)
• 密度：
  1.384±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  37
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-三氟甲基吡唑-3-甲酸 、 8-(trifluoromethoxy)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 以88%的产率得到[8-(trifluoromethoxy)-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl]-[5-(trifluoromethyl)-1H-pyrazol-3-yl]methanone
  参考文献：
  名称：

  Identification, Structure–Activity Relationship, and Biological Characterization of 2,3,4,5-Tetrahydro-1H-pyrido[4,3-b]indoles as a Novel Class of CFTR Potentiators

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.0c01050
• 作为产物：
  描述：

  N-叔丁氧羰基-4-哌啶酮 、 4-三氟甲氧基苯肼 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 16.0h， 以8%的产率得到8-(trifluoromethoxy)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole
  参考文献：
  名称：

  [EN] COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CYSTIC FIBROSIS
  [FR] COMPOSÉS ET COMPOSITIONS POUR LE TRAITEMENT DE LA FIBROSE KYSTIQUE

  摘要：

  本发明涉及式(Ia)的化合物或其药学上可接受的盐、水合物、溶剂合物、包合物、多形体、立体异构体。进一步披露了一种包含式(Ia)的化合物的药物组合物，以及利用式(Ib)的化合物，特别是用于调节CFTR蛋白或ABC蛋白活性。

  公开号：

  WO2020012427A1

文献信息

• Inhibitors of histone deacetylase
  申请人：Anandan K. Sampath

  公开号：US20060199829A1

  公开（公告）日：2006-09-07

  Disclosed are compounds of formula I that inhibit histone deacetylase (HDAC) enzymatic activity, pharmaceutical compositions comprising such compounds, as well as methods to treat conditions, particularly proliferative conditions, mediated at least in part by HDAC, wherein A, W, W 1 , W 2 , Ar 2 , and G are described herein.

  本发明涉及公式I的化合物，其抑制组蛋白去乙酰化酶（HDAC）酶活性，包括这样的化合物的制药组合物，以及用于治疗至少部分由HDAC介导的疾病，特别是增殖性疾病的方法，其中A，W，W1，W2，Ar2和G如本文所述。
• METHODS FOR INHIBITION OF CELL PROLIFERATION, SYNERGISTIC TRANSCRIPTION MODULES AND USES THEREOF
  申请人：Iavarone Antonio

  公开号：US20130156795A1

  公开（公告）日：2013-06-20

  The invention provides for methods for treating nervous system cancers in a subject. The invention further provides methods for treating nervous system tumor cell invasion, migration, proliferation, and angiogenesis associated with nervous system tumors.
• COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CYSTIC FIBROSIS
  申请人：Fondazione Istituto Italiano Di Tecnologia

  公开号：US20210292324A1

  公开（公告）日：2021-09-23

  The present invention relates to compounds of Formula (Ia) or pharmaceutically acceptable salts, hydrates, solvates, clathrates, polymorphs, stereoisomers thereof. It further discloses a pharmaceutical composition comprising the compounds of Formula (Ia) and the use of compounds of Formula (Ib), in particular to modulate CFTR protein or ABC protein activities.
• US7772245B2
  申请人：——

  公开号：US7772245B2

  公开（公告）日：2010-08-10
• 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.