2-[[(butylamino)carbonyl]amino]-4-methyl-N-(2,4,6-trimethylphenyl)-5-thiazolecarboxamide

• 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: 2-[[(butylamino)carbonyl]amino]-4-methyl-N-(2,4,6-trimethylphenyl)-5-thiazolecarboxamide
• 英文别名: 2-[(butylcarbamoyl)amino]-4-methyl-N-(2,4,6-trimethylphenyl)-1,3-thiazole-5-carboxamide；2-(butylcarbamoylamino)-4-methyl-N-(2,4,6-trimethylphenyl)-1,3-thiazole-5-carboxamide
• 化学式: C₁₉H₂₆N₄O₂S
• 分子量: 374.507
• InChiKey: ANOOKLPIDKBMTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-amino-N-(2,4,6-trimethylphenyl)-4-methyl-5-thiazolecarboxamide 以 四氢呋喃 为溶剂， 生成 2-[[(butylamino)carbonyl]amino]-4-methyl-N-(2,4,6-trimethylphenyl)-5-thiazolecarboxamide
  参考文献：
  名称：

  Discovery and initial SAR of 2-amino-5-carboxamidothiazoles as inhibitors of the Src-family kinase p56Lck

  摘要：

  A novel series of 2-amino-5-5carboxamidothiazoles were identified as inhibitors of Lck. Structure-activity studies demonstrate the structural requirements for potent Lck activity. Cyclopropylamide 11d is a potent Lck inhibitor having submicromolar activity in a PBL proliferation assay. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.08.054

文献信息

• 2-Aminothiazole as a Novel Kinase Inhibitor Template. Structure−Activity Relationship Studies toward the Discovery of <i>N</i>-(2-Chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1- piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (Dasatinib, BMS-354825) as a Potent <i>pan</i>-Src Kinase Inhibitor
  作者：Jagabandhu Das、Ping Chen、Derek Norris、Ramesh Padmanabha、James Lin、Robert V. Moquin、Zhongqi Shen、Lynda S. Cook、Arthur M. Doweyko、Sidney Pitt、Suhong Pang、Ding Ren Shen、Qiong Fang、Henry F. de Fex、Kim W. McIntyre、David J. Shuster、Kathleen M. Gillooly、Kamelia Behnia、Gary L. Schieven、John Wityak、Joel C. Barrish

  DOI：10.1021/jm060727j

  日期：2006.11.1

  2-aminothiazole (1) was discovered as a novel Src family kinase inhibitor template through screening of our internal compound collection. Optimization through successive structure-activity relationship iterations identified analogs 2 (Dasatinib, BMS-354825) and 12m as pan-Src inhibitors with nanomolar to subnanomolar potencies in biochemical and cellular assays. Molecular modeling was used to construct

  通过筛选我们的内部化合物集合，发现了2-氨基噻唑（1）作为一种新型Src家族激酶抑制剂模板。通过连续的结构-活性关系迭代进行的优化确定了类似物2（Dasatinib，BMS-354825）和12m是在生化和细胞分析中具有纳摩尔至亚纳摩尔浓度的pan-Src抑制剂。分子模型被用来构建推定的结合模型，以抑制这类化合物对Lck的抑制作用。该模型提出的关键氢键相互作用的框架与随后公布的与结构相似的Abl激酶结合的2的晶体结构一致。此类抑制剂的口服药效为12m，可在小鼠体内体外抑制促炎细胞因子IL-2（ED50约为5 mg / kg），并在急性小鼠炎症模型中降低TNF水平（LPS抑制90％） LPS给药前2小时以60 mg / kg口服给药时，TNF-α诱导的TNFα产生）。当每天两次以0.3和3 mg / kg口服给药时，在已确诊疾病的大鼠的慢性佐剂性关节炎模型中进一步证明了12m的口服功效。达沙
• Cyclic protein tyrosine kinase inhibitors
  申请人：——

  公开号：US20040054186A1

  公开（公告）日：2004-03-18

  Novel cyclic compounds and salts thereof, pharmaceutical compositions containing such compounds, and methods of using such compounds in the treatment of protein tyrosine kinase-associated disorders such as immunologic and oncologic disorders.

  新型环状化合物及其盐类，含有此类化合物的药物组合物，以及使用此类化合物治疗蛋白质酪氨酸激酶相关疾病，如免疫和肿瘤疾病的方法。
• Synergistic methods and compositions for treating cancer
  申请人：——

  公开号：US20040209930A1

  公开（公告）日：2004-10-21

  Combination therapies using IGF1R inhibitors in combination with additional kinase inhibitors are described for the synergistic treatment of cancer.

  描述了使用IGF1R抑制剂与其他激酶抑制剂结合的联合疗法，用于癌症的协同治疗。
• [EN] CYCLIC PROTEIN TYROSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS CYCLIQUES DE PROTEINE TYROSINE KINASE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2000062778A1

  公开（公告）日：2000-10-26

  Novel cyclic compounds and salts thereof, pharmaceutical compositions containing such compounds, and methods of using such compounds in the treatment of protein tyrosine kinase-associated disorders such as immunologic and oncologic disorders.

  小说环状化合物及其盐，含有这些化合物的制药组合物，以及使用这些化合物治疗蛋白酪氨酸激酶相关疾病（如免疫和肿瘤疾病）的方法。
• CYCLIC PROTEIN TYROSINE KINASE INHIBITORS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20140206691A1

  公开（公告）日：2014-07-24

  Novel cyclic compounds and salts thereof, pharmaceutical compositions containing such compounds, and methods of using such compounds in the treatment of protein tyrosine kinase-associated disorders such as immunologic and oncologic disorders.

  新型环状化合物及其盐，含有这种化合物的药物组合物，以及使用这种化合物治疗蛋白酪氨酸激酶相关疾病（如免疫和肿瘤疾病）的方法。