3-((3-(3-aminophenyl)-1H-pyrazol-5-yl)carbamoyl)benzoic acid | 1327167-40-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-((3-(3-aminophenyl)-1H-pyrazol-5-yl)carbamoyl)benzoic acid
• CAS: 1327167-40-7
• 化学式: C₁₇H₁₄N₄O₃
• 分子量: 322.323
• InChiKey: JSLALIOCZPXYLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.61
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  121.1
• 氢给体数：
  4.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-((3-(3-aminophenyl)-1H-pyrazol-5-yl)carbamoyl)benzoic acid 、 苯磺酰氯 在 吡啶 作用下， 以 二甲基亚砜 为溶剂， 反应 1.0h， 生成 3-[(3-(3-[(phenylsulfonyl)amino]phenyl)-1H-pyrazol-5-yl)amino]carbonylbenzoic acid
  参考文献：
  名称：

  Discovery and evaluation of 3-phenyl-1H-5-pyrazolylamine-based derivatives as potent, selective and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)

  摘要：

  Preclinical investigations and early clinical trial studies suggest that FLT3 inhibitors offer a viable therapy for acute myeloid leukemia. However, early clinical data for direct FLT3 inhibitors provided only modest results because of the failure to fully inhibit FLT3. We have designed and synthesized a novel class of 3-phenyl-1H-5-pyrazolylamine-derived compounds as FLT3 inhibitors which exhibit potent FLT3 inhibition and high selectivity toward different receptor tyrosine kinases. The structure-activity relationships led to the discovery of two series of FLT3 inhibitors, and some potent compounds within these two series exhibited comparable potency to FLT3 inhibitors sorafenib (3) and ABT-869 (4) in both wt-FLT3 enzyme inhibition and FLT3-ITD inhibition on cell growth (MOLM-13 and MV4; 11 cells). In particular, the selected compound 12a exhibited the ability to regress tumors in mouse xenograft models using MOLM-13 and MV4; 11 cells. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.016
• 作为产物：
  描述：

  3-(氯甲酰基)苯甲酸 在 吡啶 、 盐酸 、 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 13.0h， 生成 3-((3-(3-aminophenyl)-1H-pyrazol-5-yl)carbamoyl)benzoic acid
  参考文献：
  名称：

  Discovery and evaluation of 3-phenyl-1H-5-pyrazolylamine-based derivatives as potent, selective and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)

  摘要：

  Preclinical investigations and early clinical trial studies suggest that FLT3 inhibitors offer a viable therapy for acute myeloid leukemia. However, early clinical data for direct FLT3 inhibitors provided only modest results because of the failure to fully inhibit FLT3. We have designed and synthesized a novel class of 3-phenyl-1H-5-pyrazolylamine-derived compounds as FLT3 inhibitors which exhibit potent FLT3 inhibition and high selectivity toward different receptor tyrosine kinases. The structure-activity relationships led to the discovery of two series of FLT3 inhibitors, and some potent compounds within these two series exhibited comparable potency to FLT3 inhibitors sorafenib (3) and ABT-869 (4) in both wt-FLT3 enzyme inhibition and FLT3-ITD inhibition on cell growth (MOLM-13 and MV4; 11 cells). In particular, the selected compound 12a exhibited the ability to regress tumors in mouse xenograft models using MOLM-13 and MV4; 11 cells. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.016