butyl 4-[(2S)-5-tert-butoxy-2-([(4-chloro-6-phenylpyridin-2-yl)carbonyl]amino)-5-oxopentanoyl]piperazine-1-carboxylate | 1214284-58-8

• 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-2-([(4-chloro-6-phenylpyridin-2-yl)carbonyl]amino)-5-oxopentanoyl]piperazine-1-carboxylate
• 英文别名: butyl 4-[(2S)-2-[(4-chloro-6-phenylpyridine-2-carbonyl)amino]-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoyl]piperazine-1-carboxylate
• CAS: 1214284-58-8
• 化学式: C₃₀H₃₉ClN₄O₆
• 分子量: 587.116
• InChiKey: VSESQXXZWNPADX-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  41
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  butyl 4-[(2S)-5-tert-butoxy-2-([(4-chloro-6-phenylpyridin-2-yl)carbonyl]amino)-5-oxopentanoyl]piperazine-1-carboxylate 、 甲基哌啶-4-甲胺 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 生成
  参考文献：
  名称：

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

  摘要：

  Efforts to re. ne the SAR of the piperazinyl-glutamate-pyridines for more potent analogs with improved pharmacokinetic profiles are described. Exploring substituted piperidines and other ring systems at the 4-pyridyl position led to compounds with improved potency and pharmacokinetic properties over candidate I. In particular, compounds 4t and 5t were discovered with a 10-fold improvement over potency and improved pharmacokinetic profiles in both the rat and dog. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.12.110
• 作为产物：
  描述：

  butyl (S)-4-(2-amino-4-tert-butoxycarbonylbutyryl)piperazine-1-carboxylate 、 4-氯-6-苯基吡啶-2-羧酸 在 N-甲基吗啉 、 1-羟基苯并三唑 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以92%的产率得到butyl 4-[(2S)-5-tert-butoxy-2-([(4-chloro-6-phenylpyridin-2-yl)carbonyl]amino)-5-oxopentanoyl]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