3-Ethyl-19-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),17,20-octaen-14-one | 855260-29-6

• 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: 3-Ethyl-19-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),17,20-octaen-14-one
• CAS: 855260-29-6
• 化学式: C₂₂H₂₀N₄O
• 分子量: 356.427
• InChiKey: PLSBNSMGQTYAJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 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：

  呋喃甲酰氯 、 3-Ethyl-19-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),17,20-octaen-14-one 在 aluminum (III) chloride 盐酸 作用下， 以 硝基甲烷 、 二氯甲烷 、 水 为溶剂， 生成 3-Ethyl-7-(furan-2-carbonyl)-19-methyl-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17,20-octaen-14-one
  参考文献：
  名称：

  Novel fused pyrrolocarbazoles

  摘要：

  本发明总体上涉及选定的融合吡咯烷咔唑，包括其药物组合物及使用它们治疗疾病的方法。本发明还涉及用于制备这些融合吡咯烷咔唑的中间体和工艺。

  公开号：

  US20050137245A1
• 作为产物：
  描述：

  5-cyano-10-ethyl-2-methyl-2,10,11,12-tetrahydro-1,2,10-triaza-indeno[5,4-a]fluorene-4-carboxylic acid ethyl ester 在 镍 氢气 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-Ethyl-19-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),17,20-octaen-14-one
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2008.02.001

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.
• TIE-2/VEGF-R2 SAR and in vitro activity of C3-acyl dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole analogs
  作者：Ted L. Underiner、Bruce Ruggeri、Lisa Aimone、Mark Albom、Thelma Angeles、Hong Chang、Robert L. Hudkins、Kathryn Hunter、Kurt Josef、Candy Robinson、Linda Weinberg、Shi Yang、Allison Zulli

  DOI：10.1016/j.bmcl.2008.02.069

  日期：2008.4

  Orally bioavailable, dual inhibitors of TIE-2/VEGF-R2 were identified by elaborating the C3/N13 SAR around a fused pyrrolodihydroindazolocarbazole scaffold. Analogs bearing a C3-thiophencarbonyl group were evaluated in enzymatic and cellular biochemical assays; two orally bioavailable analogs were further pro. led in functional assays and found to inhibit microvessel growth in rat aortic explant cultures and inhibit Ang-1-stimulated chemotaxis of HUVECs. (C) 2008 Elsevier Ltd. All rights reserved.
• Novel fused pyrrolocarbazoles
  申请人：Hudkins L. Robert

  公开号：US20050137245A1

  公开（公告）日：2005-06-23

  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.

  本发明总体上涉及选定的融合吡咯烷咔唑，包括其药物组合物及使用它们治疗疾病的方法。本发明还涉及用于制备这些融合吡咯烷咔唑的中间体和工艺。
• 8-THP-DHI analogs as potent Type I dual TIE-2/VEGF-R2 receptor tyrosine kinase inhibitors
  作者：Robert L. Hudkins、Allison L. Zulli、Ted L. Underiner、Thelma S. Angeles、Lisa D. Aimone、Sheryl L. Meyer、Daniel Pauletti、Hong Chang、Elena V. Fedorov、Steven C. Almo、Alexander A. Fedorov、Bruce A. Ruggeri

  DOI：10.1016/j.bmcl.2010.04.021

  日期：2010.6

  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.