butyl 4-[(2S)-5-tert-butoxy-5-oxo-2-(([6-phenyl-4-(piperidin-4-yloxy)pyridin-2-yl]carbonyl)amino)pentanoyl]piperazine-1-carboxylate | 1214285-51-4

• 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: butyl 4-[(2S)-5-tert-butoxy-5-oxo-2-(([6-phenyl-4-(piperidin-4-yloxy)pyridin-2-yl]carbonyl)amino)pentanoyl]piperazine-1-carboxylate
• 英文别名: butyl 4-[(2S)-5-[(2-methylpropan-2-yl)oxy]-5-oxo-2-[(6-phenyl-4-piperidin-4-yloxypyridine-2-carbonyl)amino]pentanoyl]piperazine-1-carboxylate
• CAS: 1214285-51-4
• 化学式: C₃₅H₄₉N₅O₇
• 分子量: 651.803
• InChiKey: OYYXZWPOUHTWFV-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  47
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  139
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  butyl 4-[(2S)-5-tert-butoxy-5-oxo-2-(([6-phenyl-4-(piperidin-4-yloxy)pyridin-2-yl]carbonyl)amino)pentanoyl]piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (4S)-5-[4-(butoxycarbonyl)piperazin-1-yl]-5-oxo-4-(([6-phenyl-4-(piperidin-4-yloxy)pyridin-2-yl]carbonyl)amino)pentanoic acid
  参考文献：
  名称：

  Piperazinyl-glutamate-pyridines as potent orally bioavailable P2Y12 antagonists for inhibition of platelet aggregation

  摘要：

  Polymer-assisted solution-phase (PASP) parallel library synthesis was used to discover a piperazinyl-glutamate-pyridine as a P2Y(12) antagonist. Exploitation of this lead provided compounds with excellent inhibition of platelet aggregation as measured in a human platelet rich plasma (PRP) assay. Pharmacokinetic and physiochemical properties were optimized leading to compound (4S)-4-[({4-[4-(methoxymethyl)piperidin-1-yl]-6-phenylpyridin-2-yl} carbonyl)amino]-5-oxo-5-{4-[(pentyloxy) carbonyl]piperazin-1-yl}pentanoic acid 22J with good human PRP potency, selectivity, in vivo efficacy and oral bioavailability. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.06.075
• 作为产物：
  描述：

  butyl 4-[(2S)-2-(([4-((1-[(benzyloxy)carbonyl]piperidin-4-yl)oxy)-6-phenylpyridin-2-yl]carbonyl)amino)-5-tert-butoxy-5-oxopentanoyl]piperazine-1-carboxylate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以98%的产率得到butyl 4-[(2S)-5-tert-butoxy-5-oxo-2-(([6-phenyl-4-(piperidin-4-yloxy)pyridin-2-yl]carbonyl)amino)pentanoyl]piperazine-1-carboxylate
  参考文献：
  名称：

  Piperazinyl Glutamate Pyridines as Potent Orally Bioavailable P2Y₁₂ Antagonists for Inhibition of Platelet Aggregation

  摘要：

  Polymer-assisted solution-phase (PASP) parallel library synthesis was used to discover a piperazinyl glutamate pyridine as a P2Y(12) antagonist. Exploitation of this lead provided compounds with excellent inhibition of platelet aggregation its measured in a human platelet rich plasma (PRP) assay. Pharmacokinetic and physiochemical properties were optimized through modifications at the 4-position or the pyridine ring and the terminal nitrogen of the piperazine ring, leading to compound (4S)4-[({4-[4-(methoxymethyl)piperdin-1-yl]-6-phenylpyridin-2-yl}carbonyl)amino]-5-oxo-5-{4-[(pentyloxy)carbonyl]piperazin-1-yl}pentanoic acid 47s with good human PRP potency, selectivity, in vivo efficacy, and oral bioavallability. Compound 47s was selected for further preclinical evaluations.

  DOI：

  10.1021/jm901518t

文献信息

• Piperazinyl Glutamate Pyridines as Potent Orally Bioavailable P2Y₁₂ Antagonists for Inhibition of Platelet Aggregation
  作者：John J. Parlow、Mary W. Burney、Brenda L. Case、Thomas J. Girard、Kerri A. Hall、Peter K. Harris、Ronald R. Hiebsch、Rita M. Huff、Rhonda M. Lachance、Deborah A. Mischke、Stephen R. Rapp、Rhonda S. Woerndle、Michael D. Ennis

  DOI：10.1021/jm901518t

  日期：2010.3.11

  Polymer-assisted solution-phase (PASP) parallel library synthesis was used to discover a piperazinyl glutamate pyridine as a P2Y(12) antagonist. Exploitation of this lead provided compounds with excellent inhibition of platelet aggregation its measured in a human platelet rich plasma (PRP) assay. Pharmacokinetic and physiochemical properties were optimized through modifications at the 4-position or the pyridine ring and the terminal nitrogen of the piperazine ring, leading to compound (4S)4-[(4-[4-(methoxymethyl)piperdin-1-yl]-6-phenylpyridin-2-yl}carbonyl)amino]-5-oxo-5-4-[(pentyloxy)carbonyl]piperazin-1-yl}pentanoic acid 47s with good human PRP potency, selectivity, in vivo efficacy, and oral bioavallability. Compound 47s was selected for further preclinical evaluations.
• Piperazinyl-glutamate-pyridines as potent orally bioavailable P2Y12 antagonists for inhibition of platelet aggregation
  作者：John J. Parlow、Mary W. Burney、Brenda L. Case、Thomas J. Girard、Kerri A. Hall、Ronald R. Hiebsch、Rita M. Huff、Rhonda M. Lachance、Deborah A. Mischke、Stephen R. Rapp、Rhonda S. Woerndle、Michael D. Ennis

  DOI：10.1016/j.bmcl.2009.06.075

  日期：2009.8

  Polymer-assisted solution-phase (PASP) parallel library synthesis was used to discover a piperazinyl-glutamate-pyridine as a P2Y(12) antagonist. Exploitation of this lead provided compounds with excellent inhibition of platelet aggregation as measured in a human platelet rich plasma (PRP) assay. Pharmacokinetic and physiochemical properties were optimized leading to compound (4S)-4-[(4-[4-(methoxymethyl)piperidin-1-yl]-6-phenylpyridin-2-yl} carbonyl)amino]-5-oxo-5-4-[(pentyloxy) carbonyl]piperazin-1-yl}pentanoic acid 22J with good human PRP potency, selectivity, in vivo efficacy and oral bioavailability. (C) 2009 Elsevier Ltd. All rights reserved.