AKI-001 | 925218-37-7

• 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: AKI-001
• 英文别名: 8-ethyl-2,5,6,12-tetrahydro-3,10,10-trimethyl-9-ocopyrazolo[4',3':6,7]cyclohepta[1,2-b]pyrrolo[2,3-f]indole；Pyrazolo(4',3':6,7)cyclohepta(1,2-b)pyrrolo(2,3-f)indol-9(2H)-one, 8-ethyl-4,5,6,8,10,12-hexahydro-3,10,10-trimethyl；5-ethyl-7,7,16-trimethyl-5,11,14,15-tetrazapentacyclo[10.8.0.02,10.04,8.013,17]icosa-1(12),2,4(8),9,13,16-hexaen-6-one
• CAS: 925218-37-7
• 化学式: C₂₁H₂₄N₄O
• 分子量: 348.448
• InChiKey: AOMMPEGZDRAGRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  64.8
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  6-Acetyl-15-ethyl-13,13-dimethyl-9,15-diazatetracyclo[8.7.0.02,8.012,16]heptadeca-1(17),2(8),10,12(16)-tetraene-7,14-dione 在 肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 AKI-001
  参考文献：
  名称：

  Pentacyclic kinase inhibitors

  摘要：

  这项发明提供了新型激酶抑制剂，可用作治疗剂，例如用于治疗恶性肿瘤，在该化合物具有一般式I的情况下，其中A、X、Y、Z、Ra、Rb、Rc、R1、R2、R3和m在此处被定义。

  公开号：

  US20070037791A1

文献信息

• 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.
• PENTACYCLIC KINASE INHIBITORS
  申请人：Genentech, Inc.

  公开号：EP1919920B1

  公开（公告）日：2011-05-18
• REGULATED BIOCIRCUIT SYSTEMS
  申请人：Obsidian Therapeutics, Inc.

  公开号：US20190192691A1

  公开（公告）日：2019-06-27

  The present invention provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.
• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.
• US7749994B2
  申请人：——

  公开号：US7749994B2

  公开（公告）日：2010-07-06