(2S)-N-[(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl]-2-[(2S)-1-[4-(methoxymethoxy)piperidin-1-yl]-1-oxo-3-phenylpropan-2-yl]oxyhexanamide | 130317-48-5

• 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: (2S)-N-[(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl]-2-[(2S)-1-[4-(methoxymethoxy)piperidin-1-yl]-1-oxo-3-phenylpropan-2-yl]oxyhexanamide
• CAS: 130317-48-5
• 化学式: C₃₆H₆₀N₂O₇
• 分子量: 632.882
• InChiKey: DBBZYJFNVAEBCZ-PJRHAEEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  45
• 可旋转键数：
  19
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S)-N-[(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl]-2-[(2S)-1-[4-(methoxymethoxy)piperidin-1-yl]-1-oxo-3-phenylpropan-2-yl]oxyhexanamide 在 三甲基溴硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以64.5%的产率得到(2S,4S)-3-oxa-2-butyl-4-<(4-hydroxypiperidin-1-yl)carbonyl>-5-phenylpentanamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane
  参考文献：
  名称：

  Nonpeptide renin inhibitors employing a novel 3-aza (or oxa)-2,4-dialkyl glutaric acid moiety as a P2/P3 amide bond replacement

  摘要：

  A new series of renin inhibitors has been developed. The inhibitors feature a novel replacement for the P2/P3 dipeptide moiety normally associated with renin inhibitors. The dipeptide replacement was a (2S,4S)-3-aza(or oxa)-2,4-di-alkylglutaric acid amide. Extensive structure-activity relationship studies determined that optimum potency was achieved when inhibitors employed a benzyl and butyl group at the C(4) and C(2) carbon position, respectively. In addition, maximum in vitro potency was obtained when the N-terminus was functionalized by incorporating a 4-(1,3-dioxabutyl)piperidine amide. SAR data suggested that the 1,3-dioxabutyl group (methoxymethyl ether) interacted by hydrogen bonding to groups in the S4 domain of renin. This hypothesis was strengthened when a 4-butylpiperidine amide was substituted and inhibitor potency decreased dramatically. Inhibitors employing this novel dipeptide mimic were prepared by coupling the glutaric acid amides with either the transition-state mimic (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (18) or the hydroxyethylene dipeptide isostere. The glutaric acid amides were prepared by two general procedures. The first procedure involved the reductive amination of alpha-amino acid esters with alpha-keto esters. The second procedure involved the displacement reaction of alpha-bromo esters or acids with alpha-amino acid amides.

  DOI：

  10.1021/jm00088a006
• 作为产物：
  描述：

  4-(1,3-dioxabutyl)piperidine 在 N-甲基吗啉 、 sodium hydride 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 反应 21.75h， 生成 (2S)-N-[(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl]-2-[(2S)-1-[4-(methoxymethoxy)piperidin-1-yl]-1-oxo-3-phenylpropan-2-yl]oxyhexanamide
  参考文献：
  名称：

  Nonpeptide renin inhibitors employing a novel 3-aza (or oxa)-2,4-dialkyl glutaric acid moiety as a P2/P3 amide bond replacement

  摘要：

  A new series of renin inhibitors has been developed. The inhibitors feature a novel replacement for the P2/P3 dipeptide moiety normally associated with renin inhibitors. The dipeptide replacement was a (2S,4S)-3-aza(or oxa)-2,4-di-alkylglutaric acid amide. Extensive structure-activity relationship studies determined that optimum potency was achieved when inhibitors employed a benzyl and butyl group at the C(4) and C(2) carbon position, respectively. In addition, maximum in vitro potency was obtained when the N-terminus was functionalized by incorporating a 4-(1,3-dioxabutyl)piperidine amide. SAR data suggested that the 1,3-dioxabutyl group (methoxymethyl ether) interacted by hydrogen bonding to groups in the S4 domain of renin. This hypothesis was strengthened when a 4-butylpiperidine amide was substituted and inhibitor potency decreased dramatically. Inhibitors employing this novel dipeptide mimic were prepared by coupling the glutaric acid amides with either the transition-state mimic (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (18) or the hydroxyethylene dipeptide isostere. The glutaric acid amides were prepared by two general procedures. The first procedure involved the reductive amination of alpha-amino acid esters with alpha-keto esters. The second procedure involved the displacement reaction of alpha-bromo esters or acids with alpha-amino acid amides.

  DOI：

  10.1021/jm00088a006