(S)-N-[4-(imidazo[2,1-b]benzothiazol-2-yl)phenyl]-2-[2-(3,5-dimethylphenyl)acetamido]-3-(4-hydroxyphenyl)propanamide | 1276020-69-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-N-[4-(imidazo[2,1-b]benzothiazol-2-yl)phenyl]-2-[2-(3,5-dimethylphenyl)acetamido]-3-(4-hydroxyphenyl)propanamide
• 英文别名: CF023；(S)-2-(3,5-dimethylphenylacetamido)-3-(4-hydroxyphenyl)-N-[4-(imidazo[2,1-b]benzothiazol-2-yl)phenyl]propanamide；(2S)-2-[[2-(3,5-dimethylphenyl)acetyl]amino]-3-(4-hydroxyphenyl)-N-(4-imidazo[2,1-b][1,3]benzothiazol-2-ylphenyl)propanamide
• CAS: 1276020-69-9
• 化学式: C₃₄H₃₀N₄O₃S
• 分子量: 574.703
• InChiKey: FVMCPDCTSVFIKD-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  42
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  124
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,5-二甲基苯乙酸 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 49.75h， 生成 (S)-N-[4-(imidazo[2,1-b]benzothiazol-2-yl)phenyl]-2-[2-(3,5-dimethylphenyl)acetamido]-3-(4-hydroxyphenyl)propanamide
  参考文献：
  名称：

  Identification of new aminoacid amides containing the imidazo[2,1-b]benzothiazol-2-ylphenyl moiety as inhibitors of tumorigenesis by oncogenic Met signaling

  摘要：

  The Met receptor tyrosine kinase is a promising target in anticancer therapies for its role during tumor evolution and resistance to treatment. It is characterized by an unusual structural plasticity as its active site accepts different inhibitor binding modes. Such feature can be exploited to identify distinct agents targeting tumor dependence and/or resistance by oncogenic Met. Here we report the identification of bioactive agents, featuring a new 4-(imidazo[2,1-b]benzothiazol-2-yl)phenyl moiety, targeting cancer cells dependent on oncogenic Met. One of these compounds (7c; Triflorcas) impairs survival, anchorage-independent growth, and in vivo tumorigenesis, without showing side effects. Our medicinal chemistry strategy was based on an in-house Met-focused library of aminoacid-amide derivatives enriched through structure-based computer modeling, taking into account the Met multiple-binding-mode feature. Altogether, our findings show how a rational structure-based drug design approach coupled to cell-based drug evaluation strategies can be applied in medicinal chemistry to identify new agents targeting a given oncogenic-dependency setting. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.10.051

文献信息

• [EN] NEW AMINOACID DERIVATIVES, THEIR PROCESS OF PREPARATION AND THEIR THERAPEUTICAL USES AS INHIBITORS OF ONCOGENIC SIGNALS BY THE MET FAMILY<br/>[FR] NOUVEAUX DÉRIVÉS D'ACIDES AMINÉS, LEUR PROCÉDÉ DE PRÉPARATION ET LEURS UTILISATIONS THÉRAPEUTIQUES COMME INHIBITEURS DE SIGNAUX ONCOGÈNES PAR LA FAMILLE MET
  申请人：UNIV AIX MARSEILLE II

  公开号：WO2011036303A1

  公开（公告）日：2011-03-31

  The present invention concerns novel aminoacids derivatives, in particular some aminoacid amides derivatives, their process of preparation and their use for inhibiting Met-triggered disorders, in particular cancer.

  这项发明涉及新型氨基酸衍生物，特别是一些氨基酸酰胺衍生物，它们的制备过程以及它们用于抑制Met引发的疾病，特别是癌症的用途。
• Novel aminoacids derivatives, their process of preparation and their therapeutical uses as MET inhibitors
  申请人：Université de la Méditerranée - Aix-Marseille II

  公开号：EP2305688A1

  公开（公告）日：2011-04-06

  The present invention concerns novel aminoacids derivatives, in particular some aminoacid amides derivatives, their process of preparation and their use for inhibiting Met-triggered disorders, in particular cancer.

  本发明涉及新颖的氨基酸衍生物，特别是一些氨基酸酰胺衍生物，它们的制备过程以及它们用于抑制Met引发的疾病，特别是癌症的用途。
• AMINOACID DERIVATIVES, THEIR PROCESS OF PREPARATION AND THEIR THERAPEUTICAL USES AS INHIBITORS OF ONCOGENIC SIGNALS BY THE MET FAMILY
  申请人：Universite D'aix-Marseille

  公开号：US20130085143A1

  公开（公告）日：2013-04-04

  Novel amino acids derivatives, in particular some amino acid amides derivatives, their process of preparation and their use for inhibiting Met-triggered disorders, in particular cancer.

  小说氨基酸衍生物，特别是一些氨基酸酰胺衍生物，它们的制备过程以及它们用于抑制Met触发的疾病，特别是癌症的用途。
• NEW AMINOACID DERIVATIVES, THEIR PROCESS OF PREPARATION AND THEIR THERAPEUTICAL USES AS INHIBITORS OF ONCOGENIC SIGNALS BY THE MET FAMILY
  申请人：Université d'Aix-Marseille

  公开号：EP2483280A1

  公开（公告）日：2012-08-08
• US8822698B2
  申请人：——

  公开号：US8822698B2

  公开（公告）日：2014-09-02