5-acetylamino-1-phenyl-1H-pyrazole-4-carboxylic acid ethyl ester | 524726-79-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-acetylamino-1-phenyl-1H-pyrazole-4-carboxylic acid ethyl ester
• 英文别名: 5-acetamido-4-carbethoxy-1-phenylpyrazole；Ethyl 5-acetamido-1-phenylpyrazole-4-carboxylate
• CAS: 524726-79-2
• 化学式: C₁₄H₁₅N₃O₃
• 分子量: 273.291
• InChiKey: RXUXBQLOSZCFKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  73.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-氨基高哌啶 、 5-acetylamino-1-phenyl-1H-pyrazole-4-carboxylic acid ethyl ester 在 三氯氧磷 作用下， 反应 2.0h， 生成 5-(azepan-1-yl)-6-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one
  参考文献：
  名称：

  Rapid hit to lead evaluation of pyrazolo[3,4-d]pyrimidin-4-one as selective and orally bioavailable mGluR1 antagonists

  摘要：

  Our HTS effort yielded a preferential mGluR1 pyrimidinone antagonist I with lead-like characteristics. Rapid hit to lead (HTL) study identified compounds with improved functional activity and selectivity such as lb with little improvements in ADME properties. Addition of an ammosulfonyl group on the N-1 aromatic ring led to 2f, a compound with similar in vitro biochemical profiles as those of lb but drastically improved in vitro ADME properties. These improvements were paralleled by rat PK study characterized by low clearance and quantitative bioavailability. Compound 2f represented a true lead-like molecule that is amenable for further lead optimization (LO) evaluation. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.028
• 作为产物：
  描述：

  在 氨 作用下， 以 甲醇 为溶剂， 以92%的产率得到5-acetylamino-1-phenyl-1H-pyrazole-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  Rapid hit to lead evaluation of pyrazolo[3,4-d]pyrimidin-4-one as selective and orally bioavailable mGluR1 antagonists

  摘要：

  Our HTS effort yielded a preferential mGluR1 pyrimidinone antagonist I with lead-like characteristics. Rapid hit to lead (HTL) study identified compounds with improved functional activity and selectivity such as lb with little improvements in ADME properties. Addition of an ammosulfonyl group on the N-1 aromatic ring led to 2f, a compound with similar in vitro biochemical profiles as those of lb but drastically improved in vitro ADME properties. These improvements were paralleled by rat PK study characterized by low clearance and quantitative bioavailability. Compound 2f represented a true lead-like molecule that is amenable for further lead optimization (LO) evaluation. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.028

文献信息

• Pathak, U. S.; Gandhi, Sudha; Rathod, I. S., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1994, vol. 33, # 8, p. 734 - 737
  作者：Pathak, U. S.、Gandhi, Sudha、Rathod, I. S.

  DOI：——

  日期：——
• Rapid hit to lead evaluation of pyrazolo[3,4-d]pyrimidin-4-one as selective and orally bioavailable mGluR1 antagonists
  作者：Xueqing Wang、Teodozyi Kolasa、Odile F. El Kouhen、Linda E. Chovan、Candace L. Black-Shaefer、Frank L. Wagenaar、Jennifer A. Garton、Robert B. Moreland、Prisca Honore、Yau Yi Lau、Peter J. Dandliker、Jorge D. Brioni、Andrew O. Stewart

  DOI：10.1016/j.bmcl.2007.05.028

  日期：2007.8

  Our HTS effort yielded a preferential mGluR1 pyrimidinone antagonist I with lead-like characteristics. Rapid hit to lead (HTL) study identified compounds with improved functional activity and selectivity such as lb with little improvements in ADME properties. Addition of an ammosulfonyl group on the N-1 aromatic ring led to 2f, a compound with similar in vitro biochemical profiles as those of lb but drastically improved in vitro ADME properties. These improvements were paralleled by rat PK study characterized by low clearance and quantitative bioavailability. Compound 2f represented a true lead-like molecule that is amenable for further lead optimization (LO) evaluation. (c) 2007 Elsevier Ltd. All rights reserved.