4-[4-({4-[(5R)-3-cyclohexyl-2-oxo-5-phenylimidazolidin-1-yl]piperidin-1-yl}methyl)phenoxy]benzoic acid | 1337568-21-4

• 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: 4-[4-({4-[(5R)-3-cyclohexyl-2-oxo-5-phenylimidazolidin-1-yl]piperidin-1-yl}methyl)phenoxy]benzoic acid
• 英文别名: 4-[4-[[4-[(5R)-3-cyclohexyl-2-oxo-5-phenyl-imidazolidin-1-yl]-1-piperidyl]methyl]phenoxy]benzoic acid；4-[4-[[4-[(5R)-3-cyclohexyl-2-oxo-5-phenylimidazolidin-1-yl]piperidin-1-yl]methyl]phenoxy]benzoic acid
• CAS: 1337568-21-4
• 化学式: C₃₄H₃₉N₃O₄
• 分子量: 553.701
• InChiKey: QKHYIMUJIVRLOX-YTTGMZPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  73.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (R)-tert-butyl (2-(1,3-dioxoisoindolin-2-yl)-1-phenylethyl)carbamate 在 吡啶 、 三乙酰氧基硼氢化钠 、 一水合肼 、 溶剂黄146 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 4-[4-({4-[(5R)-3-cyclohexyl-2-oxo-5-phenylimidazolidin-1-yl]piperidin-1-yl}methyl)phenoxy]benzoic acid
  参考文献：
  名称：

  Design of Substituted Imidazolidinylpiperidinylbenzoic Acids as Chemokine Receptor 5 Antagonists: Potent Inhibitors of R5 HIV-1 Replication

  摘要：

  The redesign of the previously reported thiophene-3-yl-methyl urea series, as a result of potential cardiotoxicity, was successfully accomplished, resulting in the identification of a novel potent series of CCR5 antagonists containing the imidazolidinylpiperidinyl scaffold. The main redesign criteria were to reduce the number of rotatable bonds and to maintain an acceptable lipophilicity to mitigate hERG inhibition. The structure activity relationship (SAR) that was developed was used to identify compounds with the best pharmacological profile to inhibit HIV-1. As a result, five advanced compounds, 6d, 6e, 6i, 6h, and 6k, were further evaluated for receptor selectivity, antiviral activity against CCR5 using (RS) HIV-1 clinical isolates, and in vitro and in vivo safety. On the basis of these results, 6d and 6h were selected for further development.

  DOI：

  10.1021/jm401101p

文献信息

• Design of Substituted Imidazolidinylpiperidinylbenzoic Acids as Chemokine Receptor 5 Antagonists: Potent Inhibitors of R5 HIV-1 Replication
  作者：Renato Skerlj、Gary Bridger、Yuanxi Zhou、Elyse Bourque、Ernest McEachern、Markus Metz、Curtis Harwig、Tong-Shuang Li、Wen Yang、David Bogucki、Yongbao Zhu、Jonathan Langille、Duane Veale、Tuya Ba、Michael Bey、Ian Baird、Alan Kaller、Maria Krumpak、David Leitch、Michael Satori、Krystyna Vocadlo、Danielle Guay、Susan Nan、Helen Yee、Jason Crawford、Gang Chen、Trevor Wilson、Bryon Carpenter、David Gauthier、Ron MacFarland、Renee Mosi、Veronique Bodart、Rebecca Wong、Simon Fricker、Dominique Schols

  DOI：10.1021/jm401101p

  日期：2013.10.24

  The redesign of the previously reported thiophene-3-yl-methyl urea series, as a result of potential cardiotoxicity, was successfully accomplished, resulting in the identification of a novel potent series of CCR5 antagonists containing the imidazolidinylpiperidinyl scaffold. The main redesign criteria were to reduce the number of rotatable bonds and to maintain an acceptable lipophilicity to mitigate hERG inhibition. The structure activity relationship (SAR) that was developed was used to identify compounds with the best pharmacological profile to inhibit HIV-1. As a result, five advanced compounds, 6d, 6e, 6i, 6h, and 6k, were further evaluated for receptor selectivity, antiviral activity against CCR5 using (RS) HIV-1 clinical isolates, and in vitro and in vivo safety. On the basis of these results, 6d and 6h were selected for further development.