3,5-二氧杂-2-,9-二氮杂螺[5.5]十一烷-9-羧酸叔丁酯 | 1245917-55-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 中文名称: 3,5-二氧杂-2-,9-二氮杂螺[5.5]十一烷-9-羧酸叔丁酯
• 英文名称: tert-butyl 3,5-dioxo-2,9-diazaspiro[5.5]undecane-9-carboxylate
• CAS: 1245917-55-8
• 化学式: C₁₄H₂₂N₂O₄
• 分子量: 282.34
• InChiKey: KTUOBYLQQOEIAE-UHFFFAOYSA-N

物化性质

• 沸点：
  485.7±45.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,5-二氧杂-2-,9-二氮杂螺[5.5]十一烷-9-羧酸叔丁酯 在 盐酸 、 N-碘代丁二酰亚胺 、 ammonium acetate 作用下， 以 1,4-二氧六环 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 2'-(3-fluoropyridin-4-yl)-3'-iodo-1',4',5',6'-tetrahydrospiro[piperidine-4,7'-pyrrolo[3,2-c]pyridine]
  参考文献：
  名称：

  [EN] HETEROCYCLIC INHIBITORS OF EGFR AND/OR HER2, FOR USE IN THE TREATMENT OF CANCER
  [FR] MÉTHODES DE TRAITEMENT DU CANCER

  摘要：

  公开号：

  WO2022076831A3
• 作为产物：
  描述：

  在 水 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 3,5-二氧杂-2-,9-二氮杂螺[5.5]十一烷-9-羧酸叔丁酯
  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

• Structure-based lead identification of ATP-competitive MK2 inhibitors
  作者：Tjeerd Barf、Allard Kaptein、Sander de Wilde、Ruud van der Heijden、Richard van Someren、Dennis Demont、Carsten Schultz-Fademrecht、Judith Versteegh、Mario van Zeeland、Nicole Seegers、Bert Kazemier、Bas van de Kar、Maaike van Hoek、Jeroen de Roos、Henri Klop、Ruben Smeets、Claudia Hofstra、Jorrit Hornberg、Arthur Oubrie

  DOI：10.1016/j.bmcl.2011.04.018

  日期：2011.6

  MK2 kinase is a promising drug discovery target for the treatment of inflammatory diseases. Here, we describe the discovery of novel MK2 inhibitors using X-ray crystallography and structure-based drug design. The lead has in vivo efficacy in a short-term preclinical model. (C) 2011 Elsevier Ltd. All rights reserved.
• 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.
• [EN] HETEROCYCLIC INHIBITORS OF EGFR AND/OR HER2, FOR USE IN THE TREATMENT OF CANCER<br/>[FR] MÉTHODES DE TRAITEMENT DU CANCER
  申请人：SCORPION THERAPEUTICS INC

  公开号：WO2022076831A3

  公开（公告）日：2022-07-07