DNA-PK抑制剂V | 404009-46-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: DNA-PK抑制剂V
• 英文名称: 1-(2-hydroxy-4-morpholin-4-ylphenyl)phenylmethanone
• 英文别名: DNA-Pki；DNA-PK inhibitor V；AMA37；1-(2-hydroxy-4-morpholin-4-yl-phenyl)-1-phenyl-methanone；(2-hydroxy-4-morpholin-4-ylphenyl)-phenylmethanone
• CAS: 404009-46-7
• 化学式: C₁₇H₁₇NO₃
• 分子量: 283.327
• InChiKey: FALILNHGILFDLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 储存条件：
  -20℃

制备方法与用途

AMA-37是一种芳基吗啉类似物，它是ATP竞争性的DNA-PK抑制剂，其IC50值分别为：0.27 μM（DNA-PK）、32 μM（p110α）、3.7 μM（p110β）和22 μM（p110γ）[1][2]。

反应信息

• 作为产物：
  描述：

  3-氯-N,N-二甲基苯甲酰胺 在 2-双环己基膦-2',6'-二甲氧基联苯 、 tris-(dibenzylideneacetone)dipalladium(0) 、 三溴化硼 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 DNA-PK抑制剂V
  参考文献：
  名称：

  通过亲核加成/ Buchwald–Hartwig胺化策略 对功能化酮进行一锅法模块化方法†

  摘要：

  提出了一种一般的一锅法，将有机锂试剂1,2-添加到酰胺中，然后用原位释放的锂酰胺进行布赫瓦尔德-哈特维格胺胺化。在这项工作中，酰胺被用作掩蔽的酮，通过添加可生成锂酰胺的有机锂试剂揭示，该酰胺适合于随后在钯催化剂存在下进行的布赫瓦尔德-哈特维格偶联反应。该方法允许以良好的产率快速，有效和原子经济地合成氨基芳基酮。

  DOI：

  10.1039/c8cc08444k

文献信息

• Materials and methods to potentiate cancer treatment
  申请人：——

  公开号：US20020165218A1

  公开（公告）日：2002-11-07

  Compounds that inhibit DNA-dependent protein kinase, compositions comprising the compounds, methods to inhibit the DNA-PK biological activity, methods to sensitize cells the agents that cause DNA lesions, and methods to potentiate cancer treatment are disclosed.

  抑制DNA依赖性蛋白激酶的化合物，包含这些化合物的组合物，抑制DNA-PK生物活性的方法，使细胞对引起DNA损伤的药物敏感的方法，以及增强癌症治疗的方法被披露。
• Methods of inhibiting leukocyte accumulation
  申请人：Diacovo G. Thomas

  公开号：US20050054614A1

  公开（公告）日：2005-03-10

  The invention relates generally to phosphoinositide 3-kinases (PI3Ks), and more particularly to methods of inhibiting leukocyte accumulation comprising selectively inhibiting phosphoinositide 3-kinase delta (PI3Kδ) activity in endothelial cells.

  本发明总体上涉及磷酸肌醇 3-激酶（PI3K），更具体地说，涉及通过选择性地抑制内皮细胞中磷酸肌醇 3-激酶δ（PI3Kδ）的活性来抑制白细胞聚集的方法。
• Methods for treating and/or preventing aberrant proliferation of hematopoietic cells
  申请人：Bouscary Didier

  公开号：US20060106038A1

  公开（公告）日：2006-05-18

  The invention relates generally to methods for treating and/or preventing aberrant proliferation of hematopoietic cells. More particularly, the invention relates to methods for treating and/or preventing aberrant proliferation of hematopoietic cells comprising selectively inhibiting phosphoinositide 3-kinase delta (PI3Kδ) activity in hematopoietic cells. The methods may be used to treat any indication involving aberrant proliferation of hematopoietic cells.

  本发明一般涉及治疗和/或预防造血细胞异常增殖的方法。更具体地说，本发明涉及治疗和/或预防造血细胞异常增殖的方法，包括选择性地抑制造血细胞中磷酸肌醇 3-激酶δ（PI3Kδ）的活性。这些方法可用于治疗任何涉及造血细胞异常增殖的病症。
• Isoform-specific phosphoinositide 3-kinase inhibitors from an arylmorpholine scaffold
  作者：Zachary A. Knight、Gary G. Chiang、Peter J. Alaimo、Denise M. Kenski、Caroline B. Ho、Kristin Coan、Robert T. Abraham、Kevan M. Shokat

  DOI：10.1016/j.bmc.2004.06.022

  日期：2004.9

  Phosphoinositide 3-kinases (PI3-Ks) are an ubiquitous class of signaling enzymes that regulate diverse cellular processes including growth, differentiation, and motility. Physiological roles of PI3-Ks have traditionally been assigned using two pharmacological inhibitors, LY294002 and wortmannin. Although these compounds are broadly specific for the PI3-K family, they show little selectivity among family members, and the development of isoform-specific inhibitors of these enzymes has been long anticipated. Herein, we prepare compounds from two classes of arylmorpholine PI3-K inhibitors and characterize their specificity against a comprehensive panel of targets within the PI3-K family. We identify multiplex inhibitors that potently inhibit distinct subsets of PI3-K isoforms, including the first selective inhibitor of p110beta/p110delta (IC50 p110beta = 0.13 muM, p110delta = 0.63 muM). We also identify trends that suggest certain PI3-K isoforms may be more sensitive to potent inhibition by arylmorpholines, thereby guiding future drug design based on this pharmacophore. (C) 2004 Elsevier Ltd. All rights reserved.
• MATERIALS AND METHODS TO POTENTIATE CANCER TREATMENT
  申请人：ICOS CORPORATION

  公开号：EP1351946A2

  公开（公告）日：2003-10-15