Ethyl 2,7,7-trimethyl-5-phenyl-4,7-dihydropyrazolo[1,5-A]pyrimidine-3-carboxylate | 1207507-51-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: Ethyl 2,7,7-trimethyl-5-phenyl-4,7-dihydropyrazolo[1,5-A]pyrimidine-3-carboxylate
• 英文别名: ethyl 2,7,7-trimethyl-5-phenyl-4H-pyrazolo[1,5-a]pyrimidine-3-carboxylate
• CAS: 1207507-51-4
• 化学式: C₁₈H₂₁N₃O₂
• 分子量: 311.384
• InChiKey: SYVLTDQFAHGZNA-UHFFFAOYSA-N

物化性质

• 沸点：
  469.7±45.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  56.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Ethyl 2,7,7-trimethyl-5-phenyl-4,7-dihydropyrazolo[1,5-A]pyrimidine-3-carboxylate 在 sodium tetrahydroborate 作用下， 以 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl (5S)-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylate
  参考文献：
  名称：

  Novel and potent calcium-sensing receptor antagonists: Discovery of (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate (TAK-075) as an orally active bone anabolic agent

  摘要：

  The calcium-sensing receptor antagonist (CaSR) has been recognized as a promising target of anabolic agents for treating osteoporosis. In the course of developing a new drug candidate for osteoporosis, we found tetrahydropyrazolopyrimidine derivative 1 to be an orally active CaSR antagonist that stimulated transient PTH secretion in rats. However, compound 1 showed poor physical and chemical stability. In order to work out this compound's chemical stability and further understand its in vivo efficacy, we focused on modifying the 2-position of the tetrahydropyrazolopyrimidine. As a result of chemical modification, we discovered (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate 10m (TAK-075), which showed improved solubility, chemical stability, and in vivo efficacy. Furthermore, we describe that evaluating the active metabolite is important during repeated treatment with short-acting CaSR antagonists. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.001
• 作为产物：
  描述：

  苯基(2-甲基-1-丙烯基)甲酮 、 1-甲基-5-氨基吡唑-4-羧酸乙酯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 oil 为溶剂， 反应 3.5h， 生成 Ethyl 2,7,7-trimethyl-5-phenyl-4,7-dihydropyrazolo[1,5-A]pyrimidine-3-carboxylate
  参考文献：
  名称：

  Novel and potent calcium-sensing receptor antagonists: Discovery of (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate (TAK-075) as an orally active bone anabolic agent

  摘要：

  The calcium-sensing receptor antagonist (CaSR) has been recognized as a promising target of anabolic agents for treating osteoporosis. In the course of developing a new drug candidate for osteoporosis, we found tetrahydropyrazolopyrimidine derivative 1 to be an orally active CaSR antagonist that stimulated transient PTH secretion in rats. However, compound 1 showed poor physical and chemical stability. In order to work out this compound's chemical stability and further understand its in vivo efficacy, we focused on modifying the 2-position of the tetrahydropyrazolopyrimidine. As a result of chemical modification, we discovered (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate 10m (TAK-075), which showed improved solubility, chemical stability, and in vivo efficacy. Furthermore, we describe that evaluating the active metabolite is important during repeated treatment with short-acting CaSR antagonists. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.001