2-Chloro-5,6,8,9,10,11-hexahydro-3,8,11-triaza-benzo[a]fluoren-7-one | 1265004-80-5

• 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: 2-Chloro-5,6,8,9,10,11-hexahydro-3,8,11-triaza-benzo[a]fluoren-7-one
• 英文别名: 4-chloro-5,13,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(10),2,4,6,11(16)-pentaen-12-one
• CAS: 1265004-80-5
• 化学式: C₁₄H₁₂ClN₃O
• 分子量: 273.722
• InChiKey: FGNBVCODYZSPLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  57.8
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-4-(4-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)benzyl)morpholine 、 2-Chloro-5,6,8,9,10,11-hexahydro-3,8,11-triaza-benzo[a]fluoren-7-one 在 SiO2 、 二氯甲烷,丙烷-2-酮 作用下， 生成 2-[(E)-2-(4-{morpholin-4-ylmethyl}phenyl)vinyl]-8,9,10,11-tetrahydro-3,8,11-triazabenzo[a]fluoren-7-one
  参考文献：
  名称：

  ORGANIC COMPOUNDS

  摘要：

  化合物(I)的公式或其药学上可接受的盐或前药酯：其中，基团R1、R2、R3、R7和X如规范所定义。

  公开号：

  US20100069360A1
• 作为产物：
  描述：

  6-bromo-3-chloro-7,8-dihydroisoquinolin-5(6H)-one 、 2,4-哌啶二酮 在 ammonium acetate 作用下， 以 甲醇 为溶剂， 反应 12.0h， 生成 2-Chloro-5,6,8,9,10,11-hexahydro-3,8,11-triaza-benzo[a]fluoren-7-one
  参考文献：
  名称：

  In vivo and in vitro SAR of tetracyclic MAPKAP-K2 (MK2) inhibitors. Part II

  摘要：

  Spirocyclopropane- and spiroazetidine-substituted tetracycles 13D-E and 16A are described as orally active MK2 inhibitors. The spiroazetidine derivatives are potent MK2 inhibitors with IC(50) <3 nM and inhibit the release of TNF alpha (IC(50)<0.3 mu M) from hPBMCs and hsp27 phosphorylation in anisomycin stimulated THP-1 cells. The spirocyclopropane analogues are less potent against MK2 (IC(50) = 0.05-0.23 mu M), less potent in cells (IC(50)<1.1 mu M), but show good oral absorption. Compound 13E (100 mg/kg po; bid) showed oral activity in rAIA and mCIA, with significant reduction of swelling and histological score. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.023

文献信息

• PYRROLO ISOQUINOLINES AS KINASE INHIBITORS
  申请人：NOVARTIS AG

  公开号：EP2064212A1

  公开（公告）日：2009-06-03
• [EN] PYRROLO ISOQUINOLINES AS KINASE INHIBITORS<br/>[FR] PYRROLO ISOQUINOLINES COMME INHIBITEURS DE KINASE
  申请人：NOVARTIS AG

  公开号：WO2008025512A1

  公开（公告）日：2008-03-06

  [EN] A compound of formula (I) or a pharmaceutically acceptable salt or prodrug ester thereof: wherein the groups R1, R2, R3, R7 and X are as defined in the specification.
  [FR] L'invention concerne un composé représenté par la formule (I) ou un sel acceptable du point de vue pharmaceutique ou un ester promédicament de celui-ci : où les groupes R1, R2, R3, R7 et X sont tels que définis dans la description.
• In vivo and in vitro SAR of tetracyclic MAPKAP-K2 (MK2) inhibitors. Part II
  作者：Laszlo Revesz、Achim Schlapbach、Reiner Aichholz、Janet Dawson、Roland Feifel、Stuart Hawtin、Amanda Littlewood-Evans、Guido Koch、Markus Kroemer、Henrik Möbitz、Clemens Scheufler、Juraj Velcicky、Christine Huppertz

  DOI：10.1016/j.bmcl.2010.04.023

  日期：2010.8

  Spirocyclopropane- and spiroazetidine-substituted tetracycles 13D-E and 16A are described as orally active MK2 inhibitors. The spiroazetidine derivatives are potent MK2 inhibitors with IC(50) <3 nM and inhibit the release of TNF alpha (IC(50)<0.3 mu M) from hPBMCs and hsp27 phosphorylation in anisomycin stimulated THP-1 cells. The spirocyclopropane analogues are less potent against MK2 (IC(50) = 0.05-0.23 mu M), less potent in cells (IC(50)<1.1 mu M), but show good oral absorption. Compound 13E (100 mg/kg po; bid) showed oral activity in rAIA and mCIA, with significant reduction of swelling and histological score. (C) 2010 Elsevier Ltd. All rights reserved.
• ORGANIC COMPOUNDS
  申请人：Revesz Laszlo

  公开号：US20100069360A1

  公开（公告）日：2010-03-18

  A compound of formula (I) or a pharmaceutically acceptable salt or prodrug ester thereof: wherein the groups R1, R2, R3, R7 and X are as defined in the specification.

  化合物(I)的公式或其药学上可接受的盐或前药酯：其中，基团R1、R2、R3、R7和X如规范所定义。