7-Acetyl-19-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(9),5,7,11(15),17,20-octaen-14-one | 856693-71-5

• 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: 7-Acetyl-19-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(9),5,7,11(15),17,20-octaen-14-one
• CAS: 856693-71-5
• 化学式: C₂₆H₂₆N₄O₂
• 分子量: 426.518
• InChiKey: RWJUGKSKYOKGCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  68.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-Acetyl-19-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(9),5,7,11(15),17,20-octaen-14-one 、 乙氧基胺盐酸盐 在 potassium carbonate 作用下， 以 N-甲基吡咯烷酮 、 乙醇 为溶剂， 反应 3.0h， 生成 7-[(1E)-1-(ethoxyimino)ethyl]-19-methyl-3-(2-methylpropyl)-3,13,19,20-tetraazahexacyclo[14.7.0.0^{2,10}.0^{4,9}.0^{11,15}.0^{17,21}]tricosa-1(16),2(10),4,6,8,11(15),17,20-octaen-14-one
  参考文献：
  名称：

  Novel fused pyrrolocarbazoles

  摘要：

  本发明一般涉及选定的融合吡咯咯噻唑，包括其药物组合物以及用于治疗疾病的方法。本发明还涉及制备这些融合吡咯咯噻唑的中间体和方法。

  公开号：

  US20050143442A1
• 作为产物：
  描述：

  19-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),17,20-octaen-14-one 、 乙酰氯 在 三氯化铝 作用下， 以 甲醇 、 硝基甲烷 为溶剂， 生成 7-Acetyl-19-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(9),5,7,11(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

• 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.