4-[[5-Fluoro-4-(2-methyl-3-propan-2-ylimidazol-4-yl)pyrimidin-2-yl]amino]benzoic acid | 893554-63-7

• 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: 4-[[5-Fluoro-4-(2-methyl-3-propan-2-ylimidazol-4-yl)pyrimidin-2-yl]amino]benzoic acid
• CAS: 893554-63-7
• 化学式: C₁₈H₁₈FN₅O₂
• 分子量: 355.372
• InChiKey: MRFHFWSTPWZCTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  92.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-甲基高哌嗪 、 4-[[5-Fluoro-4-(2-methyl-3-propan-2-ylimidazol-4-yl)pyrimidin-2-yl]amino]benzoic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-fluoro-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)-N-{4-[(4-methyl-1,4-diazepan-1-yl)carbonyl]phenyl}pyrimidin-2-amine
  参考文献：
  名称：

  The discovery of AZD5597, a potent imidazole pyrimidine amide CDK inhibitor suitable for intravenous dosing

  摘要：

  The development of a novel series of imidazole pyrimidine amides as cyclin-dependent kinase (CDK) inhibitors is described. Optimisation of inhibitory potency against multiple CDK's (1, 2 and 9) resulted in imidazole pyrimidine amides with potent in vitro anti-proliferative effects against a range of cancer cell lines. Excellent physiochemical properties and large margins against inhibition of CYP isoforms and the hERG ion channel were achieved by modi. cation of lipophilicity and amine basicity. A candidate with disease model activity in human cancer cell line xenografts and with suitable physiochemical and pharmacokinetic profiles for intravenous (iv) dosing was selected for further development as AZD5597. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.102
• 作为产物：
  描述：

  ethyl 4-{[5-fluoro-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidin-2-yl]amino}benzoate 在 sodium hydroxide 、 水 作用下， 以 四氢呋喃 为溶剂， 生成 4-[[5-Fluoro-4-(2-methyl-3-propan-2-ylimidazol-4-yl)pyrimidin-2-yl]amino]benzoic acid
  参考文献：
  名称：

  The discovery of AZD5597, a potent imidazole pyrimidine amide CDK inhibitor suitable for intravenous dosing

  摘要：

  The development of a novel series of imidazole pyrimidine amides as cyclin-dependent kinase (CDK) inhibitors is described. Optimisation of inhibitory potency against multiple CDK's (1, 2 and 9) resulted in imidazole pyrimidine amides with potent in vitro anti-proliferative effects against a range of cancer cell lines. Excellent physiochemical properties and large margins against inhibition of CYP isoforms and the hERG ion channel were achieved by modi. cation of lipophilicity and amine basicity. A candidate with disease model activity in human cancer cell line xenografts and with suitable physiochemical and pharmacokinetic profiles for intravenous (iv) dosing was selected for further development as AZD5597. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.102

文献信息

• The discovery of AZD5597, a potent imidazole pyrimidine amide CDK inhibitor suitable for intravenous dosing
  作者：Clifford D. Jones、David M. Andrews、Andrew J. Barker、Kevin Blades、Paula Daunt、Simon East、Catherine Geh、Mark A. Graham、Keith M. Johnson、Sarah A. Loddick、Heather M. McFarland、Alexandra McGregor、Louise Moss、David A. Rudge、Peter B. Simpson、Michael L. Swain、Kin Y. Tam、Julie A. Tucker、Mike Walker

  DOI：10.1016/j.bmcl.2008.10.102

  日期：2008.12

  The development of a novel series of imidazole pyrimidine amides as cyclin-dependent kinase (CDK) inhibitors is described. Optimisation of inhibitory potency against multiple CDK's (1, 2 and 9) resulted in imidazole pyrimidine amides with potent in vitro anti-proliferative effects against a range of cancer cell lines. Excellent physiochemical properties and large margins against inhibition of CYP isoforms and the hERG ion channel were achieved by modi. cation of lipophilicity and amine basicity. A candidate with disease model activity in human cancer cell line xenografts and with suitable physiochemical and pharmacokinetic profiles for intravenous (iv) dosing was selected for further development as AZD5597. (C) 2008 Elsevier Ltd. All rights reserved.