6-(2-morpholin-4-yl-ethoxy)-2-(4-nitrophenyl)imidazo[2,1-b][1,3]benzothiazole | 1191251-69-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-(2-morpholin-4-yl-ethoxy)-2-(4-nitrophenyl)imidazo[2,1-b][1,3]benzothiazole
• 英文别名: 4-[2-[2-(4-Nitrophenyl)imidazo[2,1-b][1,3]benzothiazol-7-yl]oxyethyl]morpholine
• CAS: 1191251-69-0
• 化学式: C₂₁H₂₀N₄O₄S
• 分子量: 424.48
• InChiKey: NAPOQHNZMXPDJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  113
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-(2-morpholin-4-yl-ethoxy)-2-(4-nitrophenyl)imidazo[2,1-b][1,3]benzothiazole 在 氯化铵 、 铁粉 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以79%的产率得到2-(4-aminophenyl)-6-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazole
  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：

  2-(4-nitrophenyl)imidazo[2,1-b][1,3]benzothiazol-6-ol 、 N-(2-氯乙基)吗啉盐酸盐 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以79%的产率得到6-(2-morpholin-4-yl-ethoxy)-2-(4-nitrophenyl)imidazo[2,1-b][1,3]benzothiazole
  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

文献信息

• Imidazolothiazole compounds for the treatment of disease
  申请人：Bhagwat Shripad

  公开号：US20070232604A1

  公开（公告）日：2007-10-04

  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。
• [EN] PROCESS FOR THE PREPARATION OF IMIDAZO[2,1-B][1,3]BENZOTHIAZOLE DERIVATIVES<br/>[FR] PROCÉDÉ DE PRÉPARATION DE DÉRIVÉS D'IMIDAZO[2,1-B][1,3]BENZOTHIAZOLE
  申请人：AMBIT BIOSCIENCES CORP

  公开号：WO2011056939A1

  公开（公告）日：2011-05-12

  Provided herein are process for the preparation of N-(5-ferf-butyl-isoxazol-3-yl)- N'-4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,l-fe][l,3]benzothiazol-2-yl]phenyl}urea, or a pharmaceutically acceptable salt, solvate, hydrate, or polymorph thereof. N-(5-tert- Butyl-isoxazol-3-yl)-N'-4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,l-&][l,3]benzo- thiazol-2-yl]phenyl}urea is useful for treating, preventing, and/or managing diseases or conditions, including but not limited to, proliferative diseases, FLT-3 mediated diseases, and cancers. N-(5-ferf-Butyl-isoxazol-3-yl)-N'-4-[7-(2-morpholin-4-yl- ethoxy)imidazo[2,l-&][l,3]benzothiazol-2-yl]phenyl}urea is represented by the structure:

  本文提供了一种制备N-(5-tert-丁基异噁唑-3-基)-N'-4-[7-(2-吗啉-4-基-乙氧基)咪唑[2,1-f][1,3]苯并噻唑-2-基]苯基}脲，或其药学上可接受的盐、溶剂化合物、水合物或多晶形式的方法。N-(5-tert-丁基异噁唑-3-基)-N'-4-[7-(2-吗啉-4-基-乙氧基)咪唑[2,1-f][1,3]苯并噻唑-2-基]苯基}脲可用于治疗、预防和/或管理疾病或症状，包括但不限于增殖性疾病、FLT-3介导的疾病和癌症。N-(5-tert-丁基异噁唑-3-基)-N'-4-[7-(2-吗啉-4-基-乙氧基)咪唑[2,1-f][1,3]苯并噻唑-2-基]苯基}脲的结构如下所示：
• IMIDAZOLOTHIAZOLE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Apuy Julius L.

  公开号：US20120070410A1

  公开（公告）日：2012-03-22

  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.

  本发明提供了用于调节受体激酶活性的化合物、组合物和方法，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。
• 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。
• PROCESS FOR THE PREPARATION OF IMIDAZO[2,1-B][1,3]BENZOTHIAZOLE DERIVATIVES
  申请人：Gross Timothy David

  公开号：US20130005966A1

  公开（公告）日：2013-01-03

  Provided herein are process for the preparation of N-(5-ferf-butyl-isoxazol-3-yl)-N′-4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-fe][1,3]benzothiazol-2-yl]phenyl}urea, or a pharmaceutically acceptable salt, solvate, hydrate, or polymorph thereof. N-(5-tert-Butyl-isoxazol-3-yl)-N′-4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-&][1,3]benzo-thiazol-2-yl]phenyl}urea is useful for treating, preventing, and/or managing diseases or conditions, including but not limited to, proliferative diseases, FLT-3 mediated diseases, and cancers. N-(5-ferf-Butyl-isoxazol-3-yl)-N′-4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-&][1,3]benzothiazol-2-yl]phenyl}urea is represented by the structure:

  本文提供了制备N-(5-叔丁基异噁唑-3-基)-N'-4-[7-(2-吗啡啉-4-基-乙氧基)咪唑[2,1-fe][1,3]苯并噻唑-2-基]苯基}脲或其药学上可接受的盐、溶剂化合物、水合物或多晶形式的工艺。N-(5-叔丁基异噁唑-3-基)-N'-4-[7-(2-吗啡啉-4-基-乙氧基)咪唑[2,1-&][1,3]苯并噻唑-2-基]苯基}脲可用于治疗、预防和/或管理疾病或情况，包括但不限于增生性疾病、FLT-3介导的疾病和癌症。N-(5-ferf-叔丁基异噁唑-3-基)-N'-4-[7-(2-吗啡啉-4-基-乙氧基)咪唑[2,1-&][1,3]苯并噻唑-2-基]苯基}脲的结构式为：