3-hydroxy-N-(4-hydroxy-butyl)-5-(4-phenylamino-phenylamino)-isothiazole-4-carboxamidine

• 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: 3-hydroxy-N-(4-hydroxy-butyl)-5-(4-phenylamino-phenylamino)-isothiazole-4-carboxamidine
• 英文别名: 5-[4-(4-bromo-phenylamino)-phenylamino]-3-hydroxy-N-(4-hydroxy-butyl)-isothiazole-4-carboxamidine；5-[4-(4-bromoanilino)anilino]-N'-(4-hydroxybutyl)-3-oxo-1,2-thiazole-4-carboximidamide
• 化学式: C₂₀H₂₂BrN₅O₂S
• 分子量: 476.397
• InChiKey: NSBBUQDTZMHQCK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 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 3-hydroxy-N-(4-hydroxy-butyl)-5-(4-phenylamino-phenylamino)-isothiazole-4-carboxamidine
  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

• 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.
• US8067452B2
  申请人：——

  公开号：US8067452B2

  公开（公告）日：2011-11-29
• [EN] 3-HYDROXYISOTHIAZOLE-4-CARBOXAMIDINE DERIVATIVES AS CHK2 INHIBITORS<br/>[FR] DÉRIVÉS 3-HYDROXYISOTHIAZOLE-4-CARBOXAMIDINE COMME INHIBITEURS DE LA CHK2
  申请人：VALEANT PHARMACEUTICALS INT

  公开号：WO2008157802A1

  公开（公告）日：2008-12-24

  [EN] 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 (NH2) 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.
  [FR] La présente invention concerne des composés de formule (I), qui sont des inhibiteurs de la Chk2 et sont utiles comme agents de protection contre les radiations en radiothérapie anticancéreuse. L'invention concerne également un procédé in vitro de modulation de la Chk2 comprenant le traitement d'un substrat avec la Chk2 en présence de composés de formule I. L'invention concerne en outre un procédé de fabrication d'un composé de formule I comprenant les étapes consistant à : a) former une biaryl amine ayant un groupe amino (NH2) ; b) convertir le groupe amino en un groupe isothiocyanate ; c) ajouter un cyanoacétamide audit groupe isothiocyanate pour former un adduit thioamide ; d) cycliser ledit adduit thioamide pour former un isothiazole ayant un groupe cyano ; et e) ajouter une amine au dit groupe cyano pour former un groupe carboxamidine.
• Identification of novel, selective and potent Chk2 inhibitors
  作者：Gary Larson、Shunqi Yan、Huanming Chen、Frank Rong、Zhi Hong、Jim Zhen Wu

  DOI：10.1016/j.bmcl.2006.09.067

  日期：2007.1

  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.