Cycloheptandieno-(1,2)-phenylhydrazon

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Cycloheptandieno-(1,2)-phenylhydrazon
• 英文别名: 2-Phenylhydrazono-cycloheptanon-(1)；2-[(2-phenylhydrazino)methylidene]cycloheptanone；cycloheptane-1,2-dione-mono-phenylhydrazone；Cycloheptan-1,2-dion-mono-phenylhydrazon；cycloheptane-1,2-dione phenylhydrazone；Cycloheptane-1,2-dione phenylhydrazone；2-(phenylhydrazinylidene)cycloheptan-1-one
• 化学式: C₁₃H₁₆N₂O
• 分子量: 216.283
• InChiKey: BODAAKYZRNWTOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Cycloheptandieno-(1,2)-phenylhydrazon 在 硫酸 、 sodium hydride 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 13.0h， 生成 7-(hydroxymethylene)-7,8,9,10-tetrahydrocyclohepta[b]indol-6(5H)-one
  参考文献：
  名称：

  A novel necroptosis inhibitor—necrostatin-21 and its SAR study

  摘要：

  An initial structure-activity relationship study of the novel necroptosis inhibitor Nec-21 was described. Any changes of the tetracyclic scaffold were detrimental for the activity. Introduction of a substituent to 7 or 8 position (e.g., cyano or methoxy group, respectively), would increase the activity. The 7 and 8-position disubstituted compound 17b was 35-fold as potent as the lead, while EC50 reached 14 nM. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.073
• 作为产物：
  描述：

  环庚酮 在 盐酸 、 sodium methylate 、 sodium nitrite 作用下， 以 乙醚 、 水 为溶剂， 反应 19.5h， 生成 Cycloheptandieno-(1,2)-phenylhydrazon
  参考文献：
  名称：

  A Back-to-Front Fragment-Based Drug Design Search Strategy Targeting the DFG-Out Pocket of Protein Tyrosine Kinases

  摘要：

  We present a straightforward process for the discovery of novel back pocket-binding fragment molecules against protein tyrosine kinases. The approach begins by screening against the nonphosphorylated target kinase with subsequent counterscreening of hits against the phosphorylated enzyme. Back pocket-binding fragments are inactive against the phosphorylated kinase. Fragment molecules are of insufficient size to span both regions of the ATP binding pocket; thus, the outcome is binary (back pocket-binding or hinge-binding). Next, fragments with the appropriate binding profile are assayed in combination with a known hinge-binding fragment and subsequently with a known back pocket-binding fragment. Confirmation of back pocket-binding by Yonetani-Theorell plot analysis progresses candidate fragments to crystallization trials. The method is exemplified by a fragment screening campaign against vascular endothelial growth factor receptor 2, and a novel back pocket-binding fragment is presented.

  DOI：

  10.1021/ml3000403

文献信息

• [EN] INDOLE DERIVATIVE AND USE FOR TREATMENT OF CANCER<br/>[FR] DÉRIVÉ D'INDOLE ET USAGE POUR LE TRAITEMENT DU CANCER
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2005118587A1

  公开（公告）日：2005-12-15

  The present invention relates to a compound represented by the formula (I’) wherein A is a benzene ring optionally having substituents, R1, R2a and R3 are each a hydrogen atom, a hydrocarbon group optionally having substituents or a heterocyclic group optionally having substituents, R1 and R2a may form a ring via X, when R1 and R2a form a ring via X, R1 and R2a are each a bond or a divalent C1-5 acyclic hydrocarbon group optionally having substituents, and X is a bond, an oxygen atom, an optionally oxidized sulfur atom or an imino group optionally having a substituent, provided that R1, R2a and X are not bonds at the same time, or a salt thereof, and an agent for inhibiting kinase (phosphorylation enzyme), which contains this compound or a prodrug thereof. The compound of the present invention has an inhibitory activity against kinase such as a vascular endothelial growth factor receptor (VEGFR) and the like, and is useful as an agent for the prophylaxis or threatment of cancer and the like.

  本发明涉及一种由式(I')表示的化合物，其中A是一个苯环，可选地具有取代基，R1、R2a和R3分别是氢原子，可选地具有取代基的碳氢基团或可选地具有取代基的杂环基团，R1和R2a可以通过X形成环，当R1和R2a通过X形成环时，R1和R2a分别是键或可选地具有取代基的二价C1-5非环烃基团，X是键，氧原子，可选地氧化的硫原子或可选地具有取代基的亚胺基团，前提是R1、R2a和X不同时为键，或其盐，以及含有该化合物或其前药的抑制激酶（磷酸化酶）的药剂。本发明的化合物对激酶如血管内皮生长因子受体（VEGFR）等具有抑制活性，并可用作预防或治疗癌症等疾病的药剂。
• Structural Investigations on 4-Chloro-6-Phenyl-7,8,9,14-Tetrahydroquinolino [2′,3′:7,6]cyclohept[b]indoles
  作者：Ezhumalai Yamuna、Makuteswaran Sridharan、Karnam Jayarampillai Rajendra Prasad、Matthias Zeller

  DOI：10.1007/s10870-009-9668-z

  日期：2010.5

  8,9,14-tetrahydroquinolino[2′,3′:7,6]cyclohept[b]indole derivatives were obtained in one pot synthesis reactions via acid catalyzed condensation and cyclization of 1-oxo-1,2,3,4,5,10-hexahydrocyclohept[b]indoles with 2-amino-5-chlorobenzophenone in glacial acetic acid. Parent 4-chloro-6-phenyl-7,8,9,14-tetrahydroquinolino[2′,3′:7,6]cyclohept[b]indole and the 10, 11, 12 and 13-methyl derivatives all

  通过一锅合成反应，通过酸催化缩合和环化1获得了几种4-氯-6-苯基-7,8,9,14-四氢喹啉[2',3':7,6]环庚[b]吲哚衍生物-oxo-1,2,3,4,5,10-六氢环庚[b]吲哚与2-氨基-5-氯二苯甲酮在冰醋酸中。母体 4-氯-6-苯基-7,8,9,14-四氢喹啉[2',3':7,6]环庚[b]吲哚和10、11、12和13-甲基衍生物均在三斜空间群 P$$ \overline1} $$。11-甲基衍生物结晶时Z'=2，10-甲基异构体和12-甲基异构体共结晶为两个分子的固溶体，13-甲基衍生物和母体化合物各自的Z'=1。 晶胞参数对于四个结构是 a = 10.1826(8), b = 12.3918(7), c = 16.3825(8)Å, α = 91.626(1), β = 95.718(1), γ = 94.966(1)° 和 V = 2,047。7(2) Å3 为 11
• Indole Derivative and Use for Treatment of Cancer
  申请人：Nishikimi Yuji

  公开号：US20070254877A1

  公开（公告）日：2007-11-01

  The present invention relates to a compound represented by the formula wherein A is a benzene ring optionally having substituents, R 1 , R 2a and R 3 are each a hydrogen atom, a hydrocarbon group optionally having substituents or a heterocyclic group optionally having substituents, R 1 and R 2a may form a ring via X, when R 1 and R 2a form a ring via X, R 1 and R 2a are each a bond or a divalent C 1-5 acyclic hydrocarbon group optionally having substituents, and X is a bond, an oxygen atom, an optionally oxidized sulfur atom or an imino group optionally having a substituent, provided that R 1 , R 2a and X are not bonds at the same time, or a salt thereof, and an agent for inhibiting kinase (phosphorylation enzyme), which contains this compound or a prodrug thereof. The compound of the present invention has an inhibitory activity against kinase such as a vascular endothelial growth factor receptor (VEGFR) and the like, and is useful as an agent for the prophylaxis or treatment of cancer and the like.

  本发明涉及一种化合物，其表示为以下式子： 其中，A是苯环，可选地具有取代基，R1、R2a和R3分别是氢原子、可选地具有取代基的碳氢基团或可选地具有取代基的杂环基团，当R1和R2a通过X形成环时，R1和R2a可以是一个键或可选地具有取代基的双价C1-5非环烃基团，X是键、氧原子、可选地氧化的硫原子或可选地具有取代基的亚胺基团，前提是R1、R2a和X不同时为键，或其盐，以及一种抑制激酶（磷酸化酶）的药剂，其含有该化合物或其前药。 本发明的化合物具有对激酶（如血管内皮生长因子受体（VEGFR）等）的抑制活性，可用作预防或治疗癌症等疾病的药剂。
• A Back-to-Front Fragment-Based Drug Design Search Strategy Targeting the DFG-Out Pocket of Protein Tyrosine Kinases
  作者：Hidehisa Iwata、Hideyuki Oki、Kengo Okada、Terufumi Takagi、Michiko Tawada、Yasushi Miyazaki、Shinichi Imamura、Akira Hori、J. David Lawson、Mark S. Hixon、Hiroyuki Kimura、Hiroshi Miki

  DOI：10.1021/ml3000403

  日期：2012.4.12

  We present a straightforward process for the discovery of novel back pocket-binding fragment molecules against protein tyrosine kinases. The approach begins by screening against the nonphosphorylated target kinase with subsequent counterscreening of hits against the phosphorylated enzyme. Back pocket-binding fragments are inactive against the phosphorylated kinase. Fragment molecules are of insufficient size to span both regions of the ATP binding pocket; thus, the outcome is binary (back pocket-binding or hinge-binding). Next, fragments with the appropriate binding profile are assayed in combination with a known hinge-binding fragment and subsequently with a known back pocket-binding fragment. Confirmation of back pocket-binding by Yonetani-Theorell plot analysis progresses candidate fragments to crystallization trials. The method is exemplified by a fragment screening campaign against vascular endothelial growth factor receptor 2, and a novel back pocket-binding fragment is presented.
• A Pentacyclic Aurora Kinase Inhibitor (AKI-001) with High in Vivo Potency and Oral Bioavailability
  作者：Thomas E. Rawson、Matthias Rüth、Elizabeth Blackwood、Dan Burdick、Laura Corson、Jenna Dotson、Jason Drummond、Carter Fields、Guy J. Georges、Bernhard Goller、Jason Halladay、Thomas Hunsaker、Tracy Kleinheinz、Hans-Willi Krell、Jun Li、Jun Liang、Anja Limberg、Angela McNutt、John Moffat、Gail Phillips、Yingqing Ran、Brian Safina、Mark Ultsch、Leslie Walker、Christian Wiesmann、Birong Zhang、Aihe Zhou、Bing-Yan Zhu、Petra Rüger、Andrea G. Cochran

  DOI：10.1021/jm800052b

  日期：2008.8.1

  Aurora kinase inhibitors have attracted a great deal of interest as a new class of antimitotic agents. We report a novel class of Aurora inhibitors based on a pentacyclic scaffold. A prototype pentacyclic inhibitor 32 (AKI-001) derived from two early lead structures improves upon the best properties of each parent and compares favorably to a previously reported Aurora inhibitor, 39 (VX-680). The inhibitor exhibits low nanomolar potency against both Aurora A and Aurora B enzymes, excellent cellular potency (IC50 < 100 nM), and good oral bioavailability. Phenotypic cellular assays show that both Aurora A and Aurora B are inhibited at inhibitor concentrations sufficient to block proliferation. Importantly, the cellular activity translates to potent inhibition of tumor growth in vivo. An oral dose of 5 mg/kg QD is well tolerated and results in near stasis (92% TGI) in an HCT116 mouse xenograft model.