(R)-3-(4-oxopiperidin-1-yl)butyronitrile | 856931-48-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (R)-3-(4-oxopiperidin-1-yl)butyronitrile
• 英文别名: (R)-3-(4-Oxopiperidin-1-YL)butanenitrile；(3R)-3-(4-oxopiperidin-1-yl)butanenitrile
• CAS: 856931-48-1
• 化学式: C₉H₁₄N₂O
• 分子量: 166.223
• InChiKey: SISKQSXCCCYBCI-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-3-(4-oxopiperidin-1-yl)butyronitrile 在 lithium aluminium tetrahydride 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 甲基叔丁基醚 为溶剂， 反应 19.75h， 生成 (R)-6-chloro-2,4-dimethyl-N-(3-(4-((thiophen-3-ylmethyl)amino)piperidin-1-yl)butyl)nicotinamide
  参考文献：
  名称：

  Practical Convergent Laboratory-Scale Synthesis of a CCR5 Receptor Antagonist

  摘要：

  An efficient laboratory-scale synthesis has been developed for the selective CCR5 antagonist 1. The convergent route has a longest linear sequence of nine steps (Is steps overall), and has overall yields of 18-25%. The route has enabled the preparation of 550 g of 1.

  DOI：

  10.1021/op200259t
• 作为产物：
  描述：

  N-甲基-4-哌啶酮 以 乙醇 、 水 、 丙酮 为溶剂， 反应 23.17h， 生成 (R)-3-(4-oxopiperidin-1-yl)butyronitrile
  参考文献：
  名称：

  Practical Convergent Laboratory-Scale Synthesis of a CCR5 Receptor Antagonist

  摘要：

  An efficient laboratory-scale synthesis has been developed for the selective CCR5 antagonist 1. The convergent route has a longest linear sequence of nine steps (Is steps overall), and has overall yields of 18-25%. The route has enabled the preparation of 550 g of 1.

  DOI：

  10.1021/op200259t

文献信息

• Chemokine receptor binding compounds
  申请人：Zhou Yuanxi

  公开号：US20050277668A1

  公开（公告）日：2005-12-15

  The present invention relates to chemokine receptor binding compounds, pharmaceutical compositions and their use. More specifically, the present invention relates to modulators of chemokine receptor activity, preferably modulators of CCR5. These compounds demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

  本发明涉及趋化因子受体结合化合物、药物组合物及其用途。更具体地，本发明涉及趋化因子受体活性的调节剂，优选为CCR5的调节剂。这些化合物表现出对人类免疫缺陷病毒（HIV）感染靶细胞的保护效果。
• Design and synthesis of pyridin-2-ylmethylaminopiperidin-1-ylbutyl amide CCR5 antagonists that are potent inhibitors of M-tropic (R5) HIV-1 replication
  作者：Renato Skerlj、Gary Bridger、Yuanxi Zhou、Elyse Bourque、Ernest McEachern、Jonathan Langille、Curtis Harwig、Duane Veale、Wen Yang、Tongshong Li、Yongbao Zhu、Michael Bey、Ian Baird、Michael Sartori、Markus Metz、Renee Mosi、Kim Nelson、Veronique Bodart、Rebecca Wong、Simon Fricker、Ron Mac Farland、Dana Huskens、Dominique Schols

  DOI：10.1016/j.bmcl.2011.09.133

  日期：2011.12

  A series of CCR5 antagonists were optimized for potent inhibition of R5 HIV-1 replication in peripheral blood mononuclear cells. Compounds that met acceptable ADME criteria, selectivity, human plasma protein binding, potency shift in the presence of alpha-glycoprotein were evaluated in rat and dog pharmacokinetics. (C) 2011 Elsevier Ltd. All rights reserved.
• Mitigating hERG Inhibition: Design of Orally Bioavailable CCR5 Antagonists as Potent Inhibitors of R5 HIV-1 Replication
  作者：Renato Skerlj、Gary Bridger、Yuanxi Zhou、Elyse Bourque、Ernest McEachern、Sanjay Danthi、Jonathan Langille、Curtis Harwig、Duane Veale、Bryon Carpenter、Tuya Ba、Michael Bey、Ian Baird、Trevor Wilson、Markus Metz、Ron MacFarland、Renee Mosi、Veronique Bodart、Rebecca Wong、Simon Fricker、Dana Huskens、Dominique Schols

  DOI：10.1021/ml2002604

  日期：2012.3.8

  A series of CCR5 antagonists representing the thiophene-3-yl-methyl ureas were designed that met the pharmacological criteria for HIV-1 inhibition and mitigated a human ether-a-go-go related gene (hERG) inhibition liability. Reducing lipophilicity was the main design criteria used to identify compounds that did not inhibit the hERG channel, but subtle structural modifications were also important. Interestingly, within this series, compounds with low hERG inhibition prolonged the action potential duration (APD) in dog Purkinje fibers, suggesting a mixed effect on cardiac ion channels.
• CHEMOKINE RECEPTOR BINDING COMPOUNDS
  申请人：ANORMED INC.

  公开号：EP1708703A2

  公开（公告）日：2006-10-11
• EP1708703A4
  申请人：——

  公开号：EP1708703A4

  公开（公告）日：2008-04-09