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 | 1023320-39-9

• 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: 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
• CAS: 1023320-39-9
• 化学式: C₂₂H₁₈N₄O₂
• 分子量: 370.411
• InChiKey: OFVBOPAPSIWZQF-UHFFFAOYSA-N

物化性质

• 沸点：
  690.2±55.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  83.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  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 硝酸 、 溶剂黄146 、 sodium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 反应 19.0h， 生成
  参考文献：
  名称：

  具有免疫球蛋白和表皮生长因子样同源域2（VEGF-R / TIE-2）抑制剂11-（2-甲基丙基）-12,13-dihydro的泛血管内皮生长因子受体/酪氨酸激酶的合成和生物学特性-2-甲基-8-（嘧啶-2-基氨基）-4 H-吲唑并[5,4-a]吡咯并[3,4-c]咔唑-4-酮（CEP-11981）：新型肿瘤治疗剂

  摘要：

  大量证据支持抗血管生成抑制剂作为在多种实体和造血肿瘤中阻断或减弱肿瘤诱导的血管生成以及抑制原发性和转移性肿瘤生长的策略的实用性。鉴于肿瘤在其生长和传播的不同阶段需要不同的细胞因子和生长因子，因此最佳的抗血管生成治疗必须抑制多个，互补的和非冗余的血管生成靶标。11-（2-甲基丙基）-12,13-二氢-2-甲基-8-（嘧啶-2-基氨基）-4 H-吲唑并[5,4-a]吡咯并[3,4-c]咔唑-4 -一（11b，CEP-11981）是有效的多种靶标（TIE-2，VEGF-R1、2和3和FGF-R1）的口服活性抑制剂，在肿瘤血管生成和血管维持中具有不可或缺的作用。本文概述了11b的设计策略，合成以及生化和药理学概况，该研究完成了I期临床评估安全性和药代动力学的研究，从而可以启动概念验证研究。

  DOI：

  10.1021/jm201449n
• 作为产物：
  描述：

  在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 乙腈 为溶剂， 生成 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
  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

• 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。
• 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.
• NOVEL FUSED PYRROLOCARBAZOLES
  申请人：CEPHALON, INC.

  公开号：EP1704148B1

  公开（公告）日：2011-03-02
• 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
• 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.