methyl 5-oxo-1-(4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylate | 1143521-35-0

• 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: methyl 5-oxo-1-(4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylate
• 英文别名: methyl 5-oxo-1-[4-(trifluoromethyl)phenyl]-4H-pyrazole-3-carboxylate
• CAS: 1143521-35-0
• 化学式: C₁₂H₉F₃N₂O₃
• 分子量: 286.21
• InChiKey: RQHOEMYGFQIMSV-UHFFFAOYSA-N

物化性质

• 沸点：
  341.6±52.0 °C(predicted)
• 密度：
  1.44±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  59
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 5-oxo-1-(4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylate 在 titanium(IV) isopropylate 、 盐酸 、 lithium aluminium tetrahydride 、 偶氮二甲酸二异丙酯 、 戴斯-马丁氧化剂 、 三苯基膦 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 苯 为溶剂， 反应 0.5h， 生成 (R)-N-((R)-1-(5-methoxy-1-(4-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)ethyl)-1-phenylethanamine dihydrochloride
  参考文献：
  名称：

  Discovery and Optimization of Substituted 1-(1-Phenyl-1H-pyrazol-3-yl)methanamines as Potent and Efficacious Type II Calcimimetics

  摘要：

  Our efforts to discover potent, orally bioavailable type II calcimimetic agents for the treatment of secondary hyperparathyroidism focused on the development of ring constrained analogues of the known calcimimetic R-568. The structure-activity relationships of various substituted heterocycles and their effects oil the human calcium-sensing receptor are discussed. Pyrazole 15 was shown to be efficacious in a rat in vivo pharmacodynamic model.

  DOI：

  10.1021/jm9012278
• 作为产物：
  描述：

  丁炔二酸二甲酯 、 4-(三氟甲基)苯肼 在 sodium methylate 作用下， 以 乙醚 、 甲醇 为溶剂， 反应 3.5h， 以64%的产率得到methyl 5-oxo-1-(4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylate
  参考文献：
  名称：

  Discovery and Optimization of Substituted 1-(1-Phenyl-1H-pyrazol-3-yl)methanamines as Potent and Efficacious Type II Calcimimetics

  摘要：

  Our efforts to discover potent, orally bioavailable type II calcimimetic agents for the treatment of secondary hyperparathyroidism focused on the development of ring constrained analogues of the known calcimimetic R-568. The structure-activity relationships of various substituted heterocycles and their effects oil the human calcium-sensing receptor are discussed. Pyrazole 15 was shown to be efficacious in a rat in vivo pharmacodynamic model.

  DOI：

  10.1021/jm9012278

文献信息

• CALCIUM RECEPTOR MODULATING AGENTS
  申请人：Coulter Thomas S.

  公开号：US20110178133A1

  公开（公告）日：2011-07-21

  The present invention relates generally to novel calcimimetic compounds and pharmaceutical compositions comprising them. The invention also relates to methods of treating of diseases or disorders related to the function of the calcium sensing receptor using the compounds represented in Formula I.

  本发明通常涉及新型钙敏感受体激动剂化合物及包含它们的制药组合物。本发明还涉及使用公式I中所代表的化合物治疗与钙感受受体功能相关的疾病或障碍的方法。
• Calcium receptor modulating agents
  申请人：Amgen Inc.

  公开号：US08334317B2

  公开（公告）日：2012-12-18

  The present invention relates generally to novel calcimimetic compounds and pharmaceutical compositions comprising them. The invention also relates to methods of treating of diseases or disorders related to the function of the calcium sensing receptor using the compounds represented in Formula I.

  本发明涉及一种新型的钙敏感受体激动剂化合物和包含它们的药物组合物。该发明还涉及使用式I中所表示的化合物治疗与钙感受受体功能相关的疾病或疾病的方法。
• [EN] CALCIUM RECEPTOR MODULATING AGENTS<br/>[FR] AGENTS DE MODULATION DU RÉCEPTEUR DU CALCIUM
  申请人：AMGEN INC

  公开号：WO2009051718A3

  公开（公告）日：2009-06-11
• US8334317B2
  申请人：——

  公开号：US8334317B2

  公开（公告）日：2012-12-18
• Discovery and Optimization of Substituted 1-(1-Phenyl-1<i>H</i>-pyrazol-3-yl)methanamines as Potent and Efficacious Type II Calcimimetics
  作者：Steve F. Poon、David J. St. Jean、Paul E. Harrington、Charles Henley、James Davis、Sean Morony、Fred D. Lott、Jeff D. Reagan、Jenny Ying-Lin Lu、Yuhua Yang、Christopher Fotsch

  DOI：10.1021/jm9012278

  日期：2009.11.12

  Our efforts to discover potent, orally bioavailable type II calcimimetic agents for the treatment of secondary hyperparathyroidism focused on the development of ring constrained analogues of the known calcimimetic R-568. The structure-activity relationships of various substituted heterocycles and their effects oil the human calcium-sensing receptor are discussed. Pyrazole 15 was shown to be efficacious in a rat in vivo pharmacodynamic model.