5-(4-{1-cyclopropyl-1-[5-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]oxadiazol-3-yl]ethyl}phenyl)pyrimidin-2-ylamine | 1360553-79-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-(4-{1-cyclopropyl-1-[5-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]oxadiazol-3-yl]ethyl}phenyl)pyrimidin-2-ylamine
• 英文别名: 5-(4-{1-cyclopropyl-1-[5-(1-methyl-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl]ethyl}phenyl)pyrimidin-2-amine；5-[4-[1-Cyclopropyl-1-[5-(1-methylpyrazol-4-yl)-1,2,4-oxadiazol-3-yl]ethyl]phenyl]pyrimidin-2-amine
• CAS: 1360553-79-2
• 化学式: C₂₁H₂₁N₇O
• 分子量: 387.444
• InChiKey: RPOQYHASIAIZBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  29
• 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：
  109
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-(4-{1-cyclopropyl-1-[5-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]oxadiazol-3-yl]ethyl}phenyl)pyrimidin-2-ylamine 在 二乙胺 作用下， 以 正庚烷 、 异丙醇 为溶剂， 以98%的产率得到
  参考文献：
  名称：

  Synthesis, SAR, and Series Evolution of Novel Oxadiazole-Containing 5-Lipoxygenase Activating Protein Inhibitors: Discovery of 2-[4-(3-{(R)-1-[4-(2-Amino-pyrimidin-5-yl)-phenyl]-1-cyclopropyl-ethyl}-[1,2,4]oxadiazol-5-yl)-pyrazol-1-yl]-N,N-dimethyl-acetamide (BI 665915)

  摘要：

  The synthesis, structure-activity relationship (SAR), and evolution of a novel series of oxadiazole-containing 5-lipoxygenase-activating protein (FLAP) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent FLAP binding potency (IC50 < 10 nM) and potent inhibition of LTB4 synthesis in human whole blood (IC50 < 100 nM). Optimization of binding and functional potencies, as well as physicochemical properties resulted in the identification of compound 69 (BI 665915) that demonstrated an excellent cross-species drug metabolism and pharmacokinetics (DMPK) profile and was predicted to have low human clearance. In addition, 69 was predicted to have a low risk for potential drug-drug interactions due to its cytochrome P450 3A4 profile. In a murine ex vivo whole blood study, 69 demonstrated a linear dose-exposure relationship and a dose-dependent inhibition of LTB4 production.

  DOI：

  10.1021/jm501185j
• 作为产物：
  描述：

  (4-Bromo-phenyl)-cyclopropyl-acetonitrile 在 bis-triphenylphosphine-palladium(II) chloride 、 羟胺 、 sodium hydride 、 sodium carbonate 、 N,N'-羰基二咪唑 作用下， 以 N-甲基吡咯烷酮 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 32.83h， 生成 5-(4-{1-cyclopropyl-1-[5-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]oxadiazol-3-yl]ethyl}phenyl)pyrimidin-2-ylamine
  参考文献：
  名称：

  Synthesis, SAR, and Series Evolution of Novel Oxadiazole-Containing 5-Lipoxygenase Activating Protein Inhibitors: Discovery of 2-[4-(3-{(R)-1-[4-(2-Amino-pyrimidin-5-yl)-phenyl]-1-cyclopropyl-ethyl}-[1,2,4]oxadiazol-5-yl)-pyrazol-1-yl]-N,N-dimethyl-acetamide (BI 665915)

  摘要：

  The synthesis, structure-activity relationship (SAR), and evolution of a novel series of oxadiazole-containing 5-lipoxygenase-activating protein (FLAP) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent FLAP binding potency (IC50 < 10 nM) and potent inhibition of LTB4 synthesis in human whole blood (IC50 < 100 nM). Optimization of binding and functional potencies, as well as physicochemical properties resulted in the identification of compound 69 (BI 665915) that demonstrated an excellent cross-species drug metabolism and pharmacokinetics (DMPK) profile and was predicted to have low human clearance. In addition, 69 was predicted to have a low risk for potential drug-drug interactions due to its cytochrome P450 3A4 profile. In a murine ex vivo whole blood study, 69 demonstrated a linear dose-exposure relationship and a dose-dependent inhibition of LTB4 production.

  DOI：

  10.1021/jm501185j

文献信息

• OXADIAZOLE INHIBITORS OF LEUKOTRIENE PRODUCTION FOR COMBINATION THERAPY
  申请人：BYLOCK Lars Anders

  公开号：US20130195879A1

  公开（公告）日：2013-08-01

  The present invention relates to combination therapy using compound of formula (I): or pharmaceutically acceptable salts thereof, wherein R 1 -R 5 are as defined herein and an additional pharmaceutically active agent. The invention also relates to pharmaceutical compositions comprising these combinations, and methods of using these combinations in the treatment of various diseases and disorders.

  本发明涉及使用以下化合物的联合疗法（I）的公式： 或其药用可接受盐，其中R1-R5如本文所定义，并且另外包括一种药用活性剂。该发明还涉及包含这些组合物的药物组合物，以及在治疗各种疾病和紊乱中使用这些组合物的方法。
• OXADIAZOLE INHIBITORS OF LEUKOTRIENE PRODUCTION
  申请人：BARTOLOZZI Alessandra

  公开号：US20120220561A1

  公开（公告）日：2012-08-30

  The present invention relates to compound of formula (I): or pharmaceutically acceptable salts thereof, wherein R 1 -R 5 are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及式(I)的化合物或其药学上可接受的盐，其中R1-R5如本文所定义。本发明还涉及包含这些化合物的药物组合物、使用这些化合物治疗各种疾病和障碍的方法、制备这些化合物的过程以及在这些过程中有用的中间体。
• PHENYL-C-OXADIAZOLE DERIVATIVES AS INHIBITORS OF LEUKOTRIENE PRODUCTION FOR USE IN COMBINATION THERAPY
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2809321B1

  公开（公告）日：2016-11-09
• US8658661B2
  申请人：——

  公开号：US8658661B2

  公开（公告）日：2014-02-25
• US9248187B2
  申请人：——

  公开号：US9248187B2

  公开（公告）日：2016-02-02