20-Methyl-3-(2-methylpropyl)-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 | 855260-45-6

• 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-(2-methylpropyl)-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: 855260-45-6
• 化学式: C₂₄H₂₄N₄O
• 分子量: 384.481
• InChiKey: BUEFYAKFFUYMOM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  20-Methyl-3-(2-methylpropyl)-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 、 4-氯甲酰基丁酸甲酯 在 aluminum (III) chloride 作用下， 以 硝基甲烷 、 二氯甲烷 为溶剂， 生成 methyl 5-(13-isobutyl-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：

  5-cyano-11,12-dihydro-1-methyl-10-(2-methylpropyl)-indazolo[5,4-a]carbazole-4-carboxylic acid ethyl ester 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-(2-methylpropyl)-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

• Design and synthesis of dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole oximes as potent dual inhibitors of TIE-2 and VEGF-R2 receptor tyrosine kinases
  作者：Reddeppareddy Dandu、Allison L. Zulli、Edward R. Bacon、Ted Underiner、Candy Robinson、Hong Chang、Sheila Miknyoczki、Jennifer Grobelny、Bruce A. Ruggeri、Shi Yang、Mark S. Albom、Thelma S. Angeles、Lisa D. Aimone、Robert L. Hudkins

  DOI：10.1016/j.bmcl.2008.02.001

  日期：2008.3

  Fused dihydroindazolopyrrolocarbazole oximes have been identified as low nanomolar, potent dual TIE-2 and VEGF-R2 receptor tyrosine kinase inhibitors with excellent cellular potency. Development of the structure-activity relationships (SAR) led to identification of compounds 35 and 40 as potent, selective dual TIE-2/VEGF-R2 inhibitors with favorable pharmacokinetic properties. Compound 35 was orally active in tumor models with no observed toxicity. (C) 2008 Elsevier Ltd. All rights reserved.
• 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
• Fused pyrrolocarbazoles and methods for the preparation thereof
  申请人：Cephalon, Inc.

  公开号：EP2088150B1

  公开（公告）日：2012-06-06
• Novel Fused Pyrrolocarbazoles
  申请人：Hudkins L. Robert

  公开号：US20070203135A1

  公开（公告）日：2007-08-30

  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.
• NOVEL FUSED PYRROLOCARBAZOLES
  申请人：Hudkins Robert L.

  公开号：US20090186888A1

  公开（公告）日：2009-07-23

  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.