VRX 0466617

• 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: VRX 0466617
• 英文别名: 5-[4-(4-bromo-phenylamino)-phenylamino]-3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-isothiazole-4-carboxamidine；5-((4-((4-bromophenyl)amino)phenyl)amino)-3-hydroxy-N-(1-hydroxypropan-2-yl)isothiazole-4-carboximidamide；5-[4-(4-bromoanilino)anilino]-N'-(1-hydroxypropan-2-yl)-3-oxo-1,2-thiazole-4-carboximidamide
• 化学式: C₁₉H₂₀BrN₅O₂S
• 分子量: 462.37
• InChiKey: YFQDMCVTQPZMAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  137
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-Bromo-4'-isothiocyano-diphenylamin 在 氢氧化钾 、 溴 作用下， 以 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 VRX 0466617
  参考文献：
  名称：

  Identification of novel, selective and potent Chk2 inhibitors

  摘要：

  A series of isothiazole carboxamidine compounds were synthesized and discovered as novel and selective inhibitors for Chk2. They are not active against the related Chk1 kinase. The structure-activity relationship studies were performed on the scaffold, and enzymatic kinetic analysis showed they are simple ATP competitive inhibitors with K-i values as low as 11 nM for Chk2. Computer modeling studies were employed to comprehend the mechanism of action and SAR of these compounds. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.067

文献信息

• CHK2 Polymorphismus als Krebsmarker
  申请人：Universität Duisburg-Essen

  公开号：EP2226393A1

  公开（公告）日：2010-09-08

  Die Erfindung betrifft die Verwendung von Genveränderungen im humanen Gen CHK2 (CHEK2), das für die Checkpointkinase 2 kodiert, zur Vorhersage des Risikos und des Verlaufs von Krebserkrankungen und zur Vorhersage des Ansprechens auf pharmakologische oder nicht-pharmakologische Therapiemaßnahmen zur Behandlung von Krebserkrankungen sowie zur Vorhersage unerwünschter Arzneimittelwirkungen. Ferner betrifft die Erfindung die Bereitstellung von einzelnen Genvarianten, mit deren Hilfe weitere für die oben genannten Zwecke verwendbaren Genveränderungen detektiert und validiert werden können. Solche Genveränderungen können darin bestehen, dass im Promotor von CHK2 an Position -7161 eine Substitution von Guanin zu Adenin vorliegt, an Position -7235 eine Substitution von Cytosin zu Guanin, an Position -10532 eine Substitution von Guanin zu Adenin vorliegt oder an Position -10621 bis -10649 eine Deletion von 29 Basenpaaren vorliegt.

  本发明涉及利用编码检查点激酶 2 的人类基因 CHK2（CHEK2）的基因变异来预测癌症的风险和进展，预测对治疗癌症的药物或非药物治疗措施的反应，以及预测药物的不良反应。此外，本发明还涉及提供可用于检测和验证进一步基因改变的单个基因变体，这些基因改变可用于上述目的。这种基因变异可包括在 CHK2 启动子的-7161 位将鸟嘌呤替换为腺嘌呤、在-7235 位将胞嘧啶替换为鸟嘌呤、在-10532 位将鸟嘌呤替换为腺嘌呤或在-10621 至-10649 位删除 29 个碱基对。
• CHK2 POLYMORPHISMUS ALS KREBSMARKER
  申请人：Universität Duisburg-Essen

  公开号：EP2403962B1

  公开（公告）日：2016-01-06
• 3-HYDROXYISOTHIAZOLE-4-CARBOXAMIDINE DERIVATIVES AS CHK2 INHIBITORS
  申请人：Wu Jim Zhen

  公开号：US20090137041A1

  公开（公告）日：2009-05-28

  This invention provides compounds of Formula I which are inhibitors of Chk2 and are useful as a radiation protection agents in anticancer radiotherapy. A method of modulating Chk2 in vitro includes treating a substrate with Chk2 in the presence of compounds of formula I. A method of making a compound of formula I includes: a) forming a biaryl amine having an amino (NH 2 ) group; b) converting the amino group to an isothiocyanate group; c) adding a cyanoacetamide to said isothiocyanate group to form a thioamide adduct; d) cyclizing said thioamide adduct to form an isothiazole having a cyano group; and e) adding an amine to said cyano group to form a carboxamidine group.
• CHK2 POLYMORPHISM AS A CANCER MARKER
  申请人：Suffert Winfried

  公开号：US20120171671A1

  公开（公告）日：2012-07-05

  The invention relates to the use of gene modifications in the human gene CHK2 (CHEK2), which encodes the checkpoint kinase 2, for predicting the risk and progression of cancer diseases, for predicting the response to pharmacological or non-pharmacological therapeutic measures for treating cancer diseases, and for predicting undesired effects of drugs. The invention further relates to the provision of individual gene variants with the help of which further gene modifications that can be used for the aforementioned purposes can be detected and validated. Such gene modifications can comprise a substitution of adenine for guanine in position -7161 in the promoter of CHK2, a substitution of guanine for cytosine in position -7235, a substitution of adenine for guanine in position -10532, or a deletion of 29 base pairs in positions -10621 to -10649.
• US8067452B2
  申请人：——

  公开号：US8067452B2

  公开（公告）日：2011-11-29