20-Methyl-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),18-octaen-14-one | 856694-10-5

• 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: 20-Methyl-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),18-octaen-14-one
• CAS: 856694-10-5
• 化学式: C₂₀H₁₆N₄O
• 分子量: 328.373
• InChiKey: VAPZEBIMWRLQDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  62.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-氯甲酰基丁酸甲酯 、 20-Methyl-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),18-octaen-14-one 在 aluminum (III) chloride 作用下， 以 硝基甲烷 、 二氯甲烷 为溶剂， 生成 methyl 5-(3-methyl-6-oxo-2,3,6,7,8,13-hexahydro-1H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-10-yl)-5-oxopentanoate
  参考文献：
  名称：

  8-THP-DHI analogs as potent Type I dual TIE-2/VEGF-R2 receptor tyrosine kinase inhibitors

  摘要：

  A novel series of 8-(2-tetrahydropyranyl)-12,13-dihydroindazolo[5,4-a] pyrrolo[3,4-c]carbazoles (THP-DHI) was synthesized and evaluated as dual TIE-2 and VEGF-R2 receptor tyrosine kinase inhibitors. Development of the structure-activity relationships (SAR) with the support of X-ray crystallography led to identification of 7f and 7g as potent, selective dual TIE-2/VEGF-R2 inhibitors with excellent cellular potency and acceptable pharmacokinetic properties. Compounds 7f and 7g were orally active in tumor models with no observed toxicity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.021
• 作为产物：
  描述：

  Ethyl 11-cyano-17-methyl-3,16,17-triazapentacyclo[11.7.0.02,10.04,9.014,18]icosa-1(13),2(10),4,6,8,11,14(18),15-octaene-12-carboxylate 在 氢气 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 20-Methyl-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4,6,8,11(15),17(21),18-octaen-14-one
  参考文献：
  名称：

  8-THP-DHI analogs as potent Type I dual TIE-2/VEGF-R2 receptor tyrosine kinase inhibitors

  摘要：

  A novel series of 8-(2-tetrahydropyranyl)-12,13-dihydroindazolo[5,4-a] pyrrolo[3,4-c]carbazoles (THP-DHI) was synthesized and evaluated as dual TIE-2 and VEGF-R2 receptor tyrosine kinase inhibitors. Development of the structure-activity relationships (SAR) with the support of X-ray crystallography led to identification of 7f and 7g as potent, selective dual TIE-2/VEGF-R2 inhibitors with excellent cellular potency and acceptable pharmacokinetic properties. Compounds 7f and 7g were orally active in tumor models with no observed toxicity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.021

文献信息

• [EN] NOVEL FUSED PYRROLOCARBAZOLES<br/>[FR] NOUVEAUX PYRROLOCARBAZOLES FONDUS
  申请人：CEPHALON INC

  公开号：WO2005063763A1

  公开（公告）日：2005-07-14

  The present invention relates generally to selected fused pyrrolocarbazoles, including pharmaceutical compositions thereof and methods of treating diseases therewith. The present invention is also directed to intermediates and processes for making these fused pyrrolocarbazoles.

  本发明涉及选定的融合吡咯烷基咔唑，包括其医药组合物及用于治疗疾病的方法。本发明还涉及中间体和制备这些融合吡咯烷基咔唑的方法。
• Regioselective reduction of fused pyrrolocarbazoles-5,7-diones
  申请人：CEPHALON FRANCE

  公开号：EP2192121A1

  公开（公告）日：2010-06-02

  The present invention relates to a method for regioselectively reducing the maleimide compounds of formula (I). The invention also relates to C7 hydroxy lactam regioisomers of formula (II) obtainable by this method and their use for the preparation of lactams of formula (Ill) which are particularly useful as intermediate for the synthesis of fused pyrrolocarbazoles.

  本发明涉及一种选择性区域还原式降低式(I)男酰亚胺化合物的方法。本发明还涉及通过该方法获得的式(II)的C7羟基内酰胺异构体及其用于制备式(III)内酰胺的应用，该内酰胺用于合成融合的吡咯烷喹啉。
• NOVEL FUSED PYRROLOCARBAZOLES
  申请人：CEPHALON, INC.

  公开号：EP1704148B1

  公开（公告）日：2011-03-02
• FUSED PYRROLOCARBAZOLES AND METHODS FOR THE PREPARATION THEREOF
  申请人：CEPHALON, INC.

  公开号：EP1711499B1

  公开（公告）日：2009-06-10
• REGIOSELECTIVE REDUCTION OF FUSED PYRROLOCARBAZOLES-5,7-DIONES
  申请人：Cephalon France

  公开号：EP2350087B1

  公开（公告）日：2012-11-07