5-bromo-2-(ethoxycarbonyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid

• 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: 5-bromo-2-(ethoxycarbonyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid
• 英文别名: 4-bromo-7-ethoxycarbonyl-6,7,8,9-tetrahydro-5H-carbazole-1-carboxylic acid
• 化学式: C₁₆H₁₆BrNO₄
• 分子量: 366.211
• InChiKey: CZKPWMGOLAEQSK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  79.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-bromo-2-(ethoxycarbonyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid 在 ammonium hydroxide 、 1-羟基苯并三唑 、 1,2-二氯乙烷 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 16.0h， 以98%的产率得到ethyl 5-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate
  参考文献：
  名称：

  Design and synthesis of carbazole carboxamides as promising inhibitors of Bruton’s tyrosine kinase (BTK) and Janus kinase 2 (JAK2)

  摘要：

  Four series of disubstituted carbazole-1-carboxamides were designed and synthesised as inhibitors of Bruton's tyrosine kinase (BTK). 4,7- and 4,6-disubstituted carbazole-1-carboxamides were potent and selective inhibitors of BTK, while 3,7- and 3,6-disubstituted carbazole-1-carboxamides were potent and selective inhibitors of Janus kinase 2 (JAK2). (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.102
• 作为产物：
  描述：

  3-羟基苯甲酸乙酯 在 Rh/Al₂O₃ 、 氢气 、 戴斯-马丁氧化剂 作用下， 以 乙醇 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 2.5h， 生成 5-bromo-2-(ethoxycarbonyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid
  参考文献：
  名称：

  Small Molecule Reversible Inhibitors of Bruton’s Tyrosine Kinase (BTK): Structure–Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177)

  摘要：

  Bruton's tyrosine,kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous auto-immune diseases. This article will detail the structure-activity relationships (SARs) leading to a novel second generation series of potent and, selective reversible carbazole inhibitors of BTK. With an excellent pharmacokinetic profile as well as demonstrated in vivo activity and an acceptable safety profile, 7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oXo-3,4-dihydroquinazdlin-3-yl)phenyl]-9H-carbazole-1-carboxarnide 6 (BMS-935177) was selected:to advance into clinical development.

  DOI：

  10.1021/acs.jmedchem.6b00722

文献信息

• CARBAZOLE CARBOXAMIDE COMPOUNDS USEFUL AS KINASE INHIBITORS
  申请人：Liu Qingjie

  公开号：US20100160303A1

  公开（公告）日：2010-06-24

  Compounds having the formula (I), and enantiomers, and diastereomers, pharmaceutically-acceptable salts, thereof, are useful as kinase modulators, including Btk modulation.

  具有化学式(I)的化合物，以及其对映体、非对映异构体、药用可接受的盐，可用作激酶调节剂，包括Btk调节。
• Carbazole carboxamide compounds useful as kinase inhibitors
  申请人：Bristol-Myers Squibb Company

  公开号：US08084620B2

  公开（公告）日：2011-12-27

  Compounds having the formula (I), and enantiomers, and diastereomers, pharmaceutically-acceptable salts, thereof, are useful as kinase modulators, including Btk modulation.

  具有公式（I）的化合物，其对映异构体，顺反异构体，以及其药学上可接受的盐，可用作激酶调节剂，包括Btk调节。
• US8084620B2
  申请人：——

  公开号：US8084620B2

  公开（公告）日：2011-12-27
• US8362065B2
  申请人：——

  公开号：US8362065B2

  公开（公告）日：2013-01-29
• [EN] CARBAZOLE CARBOXAMIDE COMPOUNDS USEFUL AS KINASE INHIBITORS<br/>[FR] COMPOSÉS CARBAZOLE CARBOXAMIDE UTILES COMME INHIBITEURS DE KINASES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2010080481A1

  公开（公告）日：2010-07-15

  Compounds having the formula (I), and enantiomers, and diastereomers, pharmaceutically-acceptable salts, thereof, Formule (I) are useful as kinase modulators, including Btk modulation.