(R)-N(2)-isopropyl-N(5)-(3-(4-(3-methoxy-1-(thiophen-3-ylmethyl)ureido)piperidin-1-yl)butyl)-4,6-dimethylpyridine-2,5-dicarboxamide | 918141-78-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (R)-N(2)-isopropyl-N(5)-(3-(4-(3-methoxy-1-(thiophen-3-ylmethyl)ureido)piperidin-1-yl)butyl)-4,6-dimethylpyridine-2,5-dicarboxamide
• 英文别名: N2-isopropyl-N5-[(3R)-3-[4-[methoxycarbamoyl(3-thienylmethyl)amino]-1-piperidyl]butyl]-4,6-dimethyl-pyridine-2,5-dicarboxamide；5-N-[(3R)-3-[4-[methoxycarbamoyl(thiophen-3-ylmethyl)amino]piperidin-1-yl]butyl]-4,6-dimethyl-2-N-propan-2-ylpyridine-2,5-dicarboxamide
• CAS: 918141-78-3
• 化学式: C₂₈H₄₂N₆O₄S
• 分子量: 558.745
• InChiKey: UKQKNLSWCMOIOV-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  144
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (R)-3-(4-oxopiperidin-1-yl)butyronitrile 在 水 、 氢气 、 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 、 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 20.0~100.0 ℃ 、310.27 kPa 条件下， 反应 37.0h， 生成 (R)-N(2)-isopropyl-N(5)-(3-(4-(3-methoxy-1-(thiophen-3-ylmethyl)ureido)piperidin-1-yl)butyl)-4,6-dimethylpyridine-2,5-dicarboxamide
  参考文献：
  名称：

  Mitigating hERG Inhibition: Design of Orally Bioavailable CCR5 Antagonists as Potent Inhibitors of R5 HIV-1 Replication

  摘要：

  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.

  DOI：

  10.1021/ml2002604

文献信息

• Chemokine receptor binding compounds
  申请人：Zhou Yuanxi

  公开号：US20090099205A1

  公开（公告）日：2009-04-16

  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).

  本发明涉及化学因子受体结合化合物、制药组合物及其使用。更具体地，本发明涉及化学因子受体活性调节剂，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）感染靶细胞的保护作用。
• CHEMOKINE RECEPTOR BINDING COMPOUNDS
  申请人：ZHOU Yuanxi

  公开号：US20100298366A1

  公开（公告）日：2010-11-25

  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).

  本发明涉及化学因子受体结合化合物、制药组合物及其使用。更具体地，本发明涉及化学因子受体活性调节剂，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。
• US7790747B2
  申请人：——

  公开号：US7790747B2

  公开（公告）日：2010-09-07
• 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.