ethyl 3-(2-{4-[3-(5-tert-butylisoxazol-3-yl)ureido]phenyl}imidazo[2,1-b][1,3]benzothiazol-7-yl)propanoate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 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: ethyl 3-{2-[4-({[(5-tert-butylisoxazol-3-yl)amino]carbonyl}amino)phenyl]imidazo[2,1-b][1,3]benzothiazol-7-yl}propanoate；ethyl 3-[2-[4-[(5-tert-butyl-1,2-oxazol-3-yl)carbamoylamino]phenyl]imidazo[2,1-b][1,3]benzothiazol-6-yl]propanoate
• 化学式: C₂₈H₂₉N₅O₄S
• 分子量: 531.635
• InChiKey: ADELLOVHZULJDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  139
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 3-(2-{4-[3-(5-tert-butylisoxazol-3-yl)ureido]phenyl}imidazo[2,1-b][1,3]benzothiazol-7-yl)propanoate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 以99%的产率得到3-{2-[4-({[(5-tert-butylisoxazol-3-yl)amino]carbonyl}amino)phenyl]imidazo[2,1-b][1,3]benzothiazol-7-yl}propanoic acid
  参考文献：
  名称：

  Imidazolothiazole compounds for the treatment of disease

  摘要：

  提供了用于调节受体激酶活性以及用于治疗、预防或改善由受体激酶介导的一种或多种疾病或紊乱症状的化合物、组合物和方法。

  公开号：

  US20070232604A1
• 作为产物：
  描述：

  ethyl 3-[2-(4-aminophenyl)imidazo[2,1-b][1,3]benzothiazol-7-yl]propanoate 、 5-叔丁基-3-异氰酰基异噁唑 在 乙醚 作用下， 以 甲苯 为溶剂， 以to give the title compound as a white solid (5.056 g, 91%)的产率得到ethyl 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：

  Imidazolothiazole compounds for the treatment of disease

  摘要：

  提供了化合物、组合物和方法，用于调节受体激酶的活性，并用于治疗、预防或缓解由受体激酶介导的一种或多种疾病或疾病症状。

  公开号：

  US07820657B2

文献信息

• Method of using imidazolothiazole compounds for the treatment of disease
  申请人：Ambit Bioscience Corporation

  公开号：US08129374B2

  公开（公告）日：2012-03-06

  Compounds, compositions and methods are provided for modulating the activity of receptor kinases and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by receptor kinases.

  提供了化合物、组合物和方法，用于调节受体激酶的活性，以及治疗、预防或改善由受体激酶介导的一种或多种疾病或障碍的症状。
• IMIDAZOLOTHIAZOLE COMPOUNDS FOR THE TREATMENT OF DISEASE
  申请人：Bhagwat Shripad

  公开号：US20120129850A1

  公开（公告）日：2012-05-24

  Compounds, compositions and methods are provided for modulating the activity of receptor kinases and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by receptor kinases.

  提供了化合物、组合物和方法，用于调节受体激酶的活性，并用于治疗、预防或减轻由受体激酶介导的一种或多种疾病或障碍的症状。
• METHOD OF USING IMIDAZOLOTHIAZOLE COMPOUNDS FOR THE TREATMENT OF DISEASE
  申请人：Bhagwat Shripad

  公开号：US20100298313A1

  公开（公告）日：2010-11-25

  Compounds, compositions and methods are provided for modulating the activity of receptor kinases and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by receptor kinases.

  本发明提供了化合物、组合物和方法，用于调节受体激酶的活性，并用于治疗、预防或改善由受体激酶介导的一种或多种疾病或障碍的症状。
• Identification of <i>N</i>-(5-<i>tert</i>-Butyl-isoxazol-3-yl)-<i>N</i>′-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-<i>b</i>][1,3]benzothiazol-2-yl]phenyl}urea Dihydrochloride (AC220), a Uniquely Potent, Selective, and Efficacious FMS-Like Tyrosine Kinase-3 (FLT3) Inhibitor
  作者：Qi Chao、Kelly G. Sprankle、Robert M. Grotzfeld、Andiliy G. Lai、Todd A. Carter、Anne Marie Velasco、Ruwanthi N. Gunawardane、Merryl D. Cramer、Michael F. Gardner、Joyce James、Patrick P. Zarrinkar、Hitesh K. Patel、Shripad S. Bhagwat

  DOI：10.1021/jm9007533

  日期：2009.12.10

  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.
• IMIDAZOLOTHIAZOLE COMPOUNDS FOR THE TREATMENT OF PROLIFERATIVE DISEASES
  申请人：Ambit Biosciences Corporation

  公开号：EP2001892B1

  公开（公告）日：2013-04-24