4-{(S)-4-carboxy-2-[(5-{2-[(S)-2-(methylcarbamoyl)-pyrrolidin-1-yl]-2-oxo-ethoxy}-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester | 1163790-75-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-{(S)-4-carboxy-2-[(5-{2-[(S)-2-(methylcarbamoyl)-pyrrolidin-1-yl]-2-oxo-ethoxy}-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester
• 英文别名: (4S)-5-(4-ethoxycarbonylpiperazin-1-yl)-4-[[5-[2-[(2S)-2-(methylcarbamoyl)pyrrolidin-1-yl]-2-oxoethoxy]-1-phenylpyrazole-3-carbonyl]amino]-5-oxopentanoic acid
• CAS: 1163790-75-7
• 化学式: C₃₀H₃₉N₇O₉
• 分子量: 641.681
• InChiKey: UURXPCDHDPCBPQ-GMAHTHKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  46
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  193
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-{(S)-4-tert-butoxycarbonyl-2-[(5-carboxymethoxy-1-phenyl-1H-pyrazole-3-carbonyl)amino]butyryl}piperazine-1-carboxylic acid ethyl ester 在 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 1,2-二氯乙烷 、 N,N-二异丙基乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、300.01 kPa 条件下， 反应 60.33h， 生成 4-{(S)-4-carboxy-2-[(5-{2-[(S)-2-(methylcarbamoyl)-pyrrolidin-1-yl]-2-oxo-ethoxy}-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester
  参考文献：
  名称：

  Identification of High-Affinity P2Y₁₂ Antagonists Based on a Phenylpyrazole Glutamic Acid Piperazine Backbone

  摘要：

  A series of novel, highly potent P2Y(12) antagonists as inhibitors of platelet aggregation based on a phenylpyrazole glutamic acid piperazine backbone is described. Exploration of the structural requirements of the substituents by probing the structure-activity relationship along this backbone led to the discovery of the N-acetyl-(S)-proline cyclobutyl amide moiety as a highly privileged motif. Combining the most favorable substituents led to remarkably potent P2Y(12) antagonists displaying not only low nanomolar binding affinity to the P2Y(12) receptor but also a low nanomolar inhibition of platelet aggregation in the human platelet rich plasma assay with IC50 values below 50 nM. Using a homology and a three-dimensional quantitative structure-activity relationship model, a binding hypothesis elucidating the impact of several structural features was developed.

  DOI：

  10.1021/jm300771j

文献信息

• Identification of High-Affinity P2Y₁₂ Antagonists Based on a Phenylpyrazole Glutamic Acid Piperazine Backbone
  作者：Gernot Zech、Gerhard Hessler、Andreas Evers、Tilo Weiss、Peter Florian、Melitta Just、Jörg Czech、Werngard Czechtizky、Jochen Görlitzer、Sven Ruf、Markus Kohlmann、Marc Nazaré

  DOI：10.1021/jm300771j

  日期：2012.10.25

  A series of novel, highly potent P2Y(12) antagonists as inhibitors of platelet aggregation based on a phenylpyrazole glutamic acid piperazine backbone is described. Exploration of the structural requirements of the substituents by probing the structure-activity relationship along this backbone led to the discovery of the N-acetyl-(S)-proline cyclobutyl amide moiety as a highly privileged motif. Combining the most favorable substituents led to remarkably potent P2Y(12) antagonists displaying not only low nanomolar binding affinity to the P2Y(12) receptor but also a low nanomolar inhibition of platelet aggregation in the human platelet rich plasma assay with IC50 values below 50 nM. Using a homology and a three-dimensional quantitative structure-activity relationship model, a binding hypothesis elucidating the impact of several structural features was developed.