5-bromo-N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)picolinamide | 1351522-46-7

• 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: 5-bromo-N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)picolinamide
• 英文别名: 5-bromo-N-[4-[(5-tert-butyl-1,2-oxazol-3-yl)carbamoylamino]phenyl]pyridine-2-carboxamide
• CAS: 1351522-46-7
• 化学式: C₂₀H₂₀BrN₅O₃
• 分子量: 458.314
• InChiKey: NNKDHOCULXRSED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  钾 1-甲基-4-三氟硼酸三甲基哌嗪 、 5-bromo-N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)picolinamide 在 palladium diacetate 、 caesium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.17h， 以38%的产率得到N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)-5-((4-methylpiperazin-1-yl)methyl)picolinamide
  参考文献：
  名称：

  Discovery of AC710, a Globally Selective Inhibitor of Platelet-Derived Growth Factor Receptor-Family Kinases

  摘要：

  A series of potent, selective platelet-derived growth factor receptor-family kinase inhibitors was optimized starting from a globally selective lead molecule 4 through structural modifications aimed at improving the physiochemical and pharmacoldnetic properties, as exemplified by 18b. Further clearance reduction via per-methylation of the a-carbons of a solubilizing piperidine nitrogen resulted in advanced leads 22a and 22b. Results from a mouse tumor xenograft, a collagen-induced arthritis model, and a 7 day rat in vivo tolerability study culminated in the selection of compound 22b (AC710) as a preclinical development candidate.

  DOI：

  10.1021/ml300214g
• 作为产物：
  描述：

  5-溴-2-吡啶羧酸 、 1-(4-aminophenyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea 在 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 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 53.34h， 以86%的产率得到5-bromo-N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)picolinamide
  参考文献：
  名称：

  Discovery of AC710, a Globally Selective Inhibitor of Platelet-Derived Growth Factor Receptor-Family Kinases

  摘要：

  A series of potent, selective platelet-derived growth factor receptor-family kinase inhibitors was optimized starting from a globally selective lead molecule 4 through structural modifications aimed at improving the physiochemical and pharmacoldnetic properties, as exemplified by 18b. Further clearance reduction via per-methylation of the a-carbons of a solubilizing piperidine nitrogen resulted in advanced leads 22a and 22b. Results from a mouse tumor xenograft, a collagen-induced arthritis model, and a 7 day rat in vivo tolerability study culminated in the selection of compound 22b (AC710) as a preclinical development candidate.

  DOI：

  10.1021/ml300214g

文献信息

• [EN] AZOLYL UREA COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS AZOLYLE URÉE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：AMBIT BIOSCIENCES CORP

  公开号：WO2011150198A1

  公开（公告）日：2011-12-01

  Provided herein are azolyl urea compounds for treatment of CSF-1R kinase mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.

  本文提供了用于治疗CSF-1R激酶介导疾病的唑啉基脲化合物。还提供了包含这些化合物的药物组合物以及使用这些化合物和组合物的方法。
• Azolyl Urea Compounds and Methods of Use Thereof
  申请人：Liu Gang

  公开号：US20130310357A1

  公开（公告）日：2013-11-21

  Provided herein are azolyl urea compounds for treatment of CSF-1R kinase mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.

  本文提供了用于治疗CSF-1R激酶介导疾病的氮杂基脲化合物。还提供了包含这些化合物的药物组合物以及使用这些化合物和组合物的方法。
• US9296722B2
  申请人：——

  公开号：US9296722B2

  公开（公告）日：2016-03-29
• Discovery of AC710, a Globally Selective Inhibitor of Platelet-Derived Growth Factor Receptor-Family Kinases
  作者：Gang Liu、Brian T. Campbell、Mark W. Holladay、Julia M. Ford Pulido、Helen Hua、Dana Gitnick、Michael F. Gardner、Joyce James、Mike A. Breider、Daniel Brigham、Barbara Belli、Robert C. Armstrong、Daniel K. Treiber

  DOI：10.1021/ml300214g

  日期：2012.12.13

  A series of potent, selective platelet-derived growth factor receptor-family kinase inhibitors was optimized starting from a globally selective lead molecule 4 through structural modifications aimed at improving the physiochemical and pharmacoldnetic properties, as exemplified by 18b. Further clearance reduction via per-methylation of the a-carbons of a solubilizing piperidine nitrogen resulted in advanced leads 22a and 22b. Results from a mouse tumor xenograft, a collagen-induced arthritis model, and a 7 day rat in vivo tolerability study culminated in the selection of compound 22b (AC710) as a preclinical development candidate.