sodium 3-(2-{4-[3-(5-tert-butylisoxazol-3-yl)ureido]phenyl}imidazo[2,1-b][1,3]benzothiazol-7-yl)propanoate | 950769-89-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: sodium 3-(2-{4-[3-(5-tert-butylisoxazol-3-yl)ureido]phenyl}imidazo[2,1-b][1,3]benzothiazol-7-yl)propanoate
• 英文别名: 3-{2-[4-({[(5-tert-butylisoxazol-3-yl)amino]carbonyl}amino)phenyl]imidazo[2,1-b][1,3]benzothiazol-7-yl}propanoic acid sodium salt
• CAS: 950769-89-8
• 化学式: C₂₆H₂₄N₅O₄S*Na
• 分子量: 525.563
• InChiKey: WFHFHNPSBZIUMB-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.83
• 重原子数：
  37.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  124.59
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  N-乙基哌嗪 、 sodium 3-(2-{4-[3-(5-tert-butylisoxazol-3-yl)ureido]phenyl}imidazo[2,1-b][1,3]benzothiazol-7-yl)propanoate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 N-(5-tert-butylisoxazol-3-yl)-N'-(4-{7-[3-(4-ethylpiperazin-1-yl)-3-oxopropyl]imidazo[2,1-b][1,3]benzothiazol-2-yl}phenyl)urea
  参考文献：
  名称：

  Identification of N-(5-tert-Butyl-isoxazol-3-yl)-N′-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea Dihydrochloride (AC220), a Uniquely Potent, Selective, and Efficacious FMS-Like Tyrosine Kinase-3 (FLT3) Inhibitor

  摘要：

  Treatment of AM L patients with small molecule inhibitors of FLT3 kinase has been explored as a viable therapy. However, these agents arc found to be less than optimal for the treatment of AM L because of lack of sufficient potency or suboptimal oral pharmacokinetics (PK) or lack of adequate tolerability at efficacious doses. We have developed a series of extremely potent and highly selective FLT3 inhibitors with good oral PK properties. The first series Of Compounds represented by 1 (A13530) was found to be a potent and selective FLT3 kinase inhibitor with good PK properties. The aqueous solubility and oral PK properties at higher doses in rodents were found to be less than optimal for clinical development. A novel series of compounds were designed lacking the carboxamide group of 1 with an added water solubilizing group. Compound 7 (AC220) was identified front this series to be the most potent and selective FLT3 inhibitor with good pharmaceutical properties, excellent PK profile, and superior efficacy and tolerability in tumor xenograft models. Compound 7 has demonstrated a desirable safety and PK profile in humans and is currently in phase II clinical trials.

  DOI：

  10.1021/jm9007533
• 作为产物：
  描述：

  3-{2-[4-({[(5-tert-butylisoxazol-3-yl)amino]carbonyl}amino)phenyl]imidazo[2,1-b][1,3]benzothiazol-7-yl}propanoic acid 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以475 mg的产率得到sodium 3-(2-{4-[3-(5-tert-butylisoxazol-3-yl)ureido]phenyl}imidazo[2,1-b][1,3]benzothiazol-7-yl)propanoate
  参考文献：
  名称：

  Identification of N-(5-tert-Butyl-isoxazol-3-yl)-N′-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea Dihydrochloride (AC220), a Uniquely Potent, Selective, and Efficacious FMS-Like Tyrosine Kinase-3 (FLT3) Inhibitor

  摘要：

  Treatment of AM L patients with small molecule inhibitors of FLT3 kinase has been explored as a viable therapy. However, these agents arc found to be less than optimal for the treatment of AM L because of lack of sufficient potency or suboptimal oral pharmacokinetics (PK) or lack of adequate tolerability at efficacious doses. We have developed a series of extremely potent and highly selective FLT3 inhibitors with good oral PK properties. The first series Of Compounds represented by 1 (A13530) was found to be a potent and selective FLT3 kinase inhibitor with good PK properties. The aqueous solubility and oral PK properties at higher doses in rodents were found to be less than optimal for clinical development. A novel series of compounds were designed lacking the carboxamide group of 1 with an added water solubilizing group. Compound 7 (AC220) was identified front this series to be the most potent and selective FLT3 inhibitor with good pharmaceutical properties, excellent PK profile, and superior efficacy and tolerability in tumor xenograft models. Compound 7 has demonstrated a desirable safety and PK profile in humans and is currently in phase II clinical trials.

  DOI：

  10.1021/jm9007533