(6S,7S)-5-(methoxycarbonyl)-6-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxylic acid | 929548-85-6

• 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: (6S,7S)-5-(methoxycarbonyl)-6-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxylic acid
• CAS: 929548-85-6
• 化学式: C₂₂H₂₆N₂O₅
• 分子量: 398.459
• InChiKey: XSKHZGIBEKRMID-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.62
• 重原子数：
  29.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  87.15
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (6S,7S)-5-(methoxycarbonyl)-6-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxylic acid 在 羟胺 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 INCB 3619
  参考文献：
  名称：

  Design and identification of selective HER-2 sheddase inhibitors via P1′ manipulation and unconventional P2′ perturbations to induce a molecular metamorphosis

  摘要：

  In an effort to obtain a MMP selective and potent inhibitor of HER-2 sheddase (ADAM-10), the P1' group of a novel class of (6S,7S)-7-[(hydroxyamino)carbonyl]-6-carboxamide-5-azaspiro[2.5]octane-5-carboxylates was attenuated and the structure-activity relationships (SAR) will be discussed. In addition, it was discovered that unconventional perturbation of the P2' moiety could confer MMP selectivity, which was hypothesized to be a manifestation of the P2' group effecting global conformational changes. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.10.108
• 作为产物：
  描述：

  1,2-dibenzyl 3-tert-butyl (2S,3S)-5-methylenepiperidine-1,2,3-tricarboxylate 在 Pd-BaSO₄ 、 palladium diacetate N-甲基吗啉 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 (6S,7S)-5-(methoxycarbonyl)-6-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxylic acid
  参考文献：
  名称：

  Discovery of a Potent, Selective, and Orally Active Human Epidermal Growth Factor Receptor-2 Sheddase Inhibitor for the Treatment of Cancer

  摘要：

  The design, synthesis, evaluation, and identification of a novel class of (6S,7S)-N-hydroxy-6-carboxamide-5-azaspiro[2.5]octane-7-carboxamides as the first potent and selective inhibitors of human epidermal growth factor receptor-2 (HER-2) sheddase is described. Several compounds were identified that possess excellent pharmacodynamic and pharmacokinetic properties and were shown to decrease tumor size, cleaved HER-2 extracellular domain plasma levels, and potentiate the effects of the humanized anti-HER-2 monoclonal antibody (trastuzumab) in vivo in a HER-2 overexpressing cancer murine xenograft model.

  DOI：

  10.1021/jm061344o