ethyl 3-amino-5-propyl-1H-pyrazole-4-carboxylate | 1292827-45-2

• 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 3-amino-5-propyl-1H-pyrazole-4-carboxylate
• CAS: 1292827-45-2
• 化学式: C₉H₁₅N₃O₂
• 分子量: 197.237
• InChiKey: PRRAVYBOTGDGMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  81
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-amino-5-propyl-1H-pyrazole-4-carboxylate 在 sodium tetrahydroborate 、 草酰氯 、 sodium hydride 、 N,N-二甲基甲酰胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 oil 为溶剂， 反应 98.0h， 生成
  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

文献信息

• [EN] NOVEL PHOSPHOINOSITIDE 3-KINASE INHIBITOR AND PREPARATION METHOD AND USE THEREOF<br/>[FR] NOUVEAU INHIBITEUR DE PHOSPHOÏNOSITIDE 3-KINASE ET PROCÉDÉ DE PRÉPARATION ET D'UTILISATION ASSOCIÉ<br/>[ZH] 一种新型磷酸肌醇3-激酶抑制剂及其制备方法和用途
  申请人：INNOVENT BIOLOGICS SUZHOU CO LTD

  公开号：WO2019228404A1

  公开（公告）日：2019-12-05

  本发明属于药物化学领域，公开了一种新型磷酸肌醇3-激酶抑制剂及其制备方法和用途。本发明中的磷酸肌醇3-激酶(PI3K)抑制剂的结构如式I所示，具有抗肿瘤、抗神经退行性疾病、抗炎等多种药理活性。