5,6-dibenzyl 7-tert-butyl (6S,7S)-5-azaspiro[2.5]octane-5,6,7-tricarboxylate | 791834-46-3

• 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: 5,6-dibenzyl 7-tert-butyl (6S,7S)-5-azaspiro[2.5]octane-5,6,7-tricarboxylate
• 英文别名: 5-O,6-O-dibenzyl 7-O-tert-butyl (6S,7S)-5-azaspiro[2.5]octane-5,6,7-tricarboxylate
• CAS: 791834-46-3
• 化学式: C₂₈H₃₃NO₆
• 分子量: 479.573
• InChiKey: WXHRJVASLLUISW-GOTSBHOMSA-N

物化性质

• 沸点：
  595.4±50.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5,6-dibenzyl 7-tert-butyl (6S,7S)-5-azaspiro[2.5]octane-5,6,7-tricarboxylate 在 Pd-BaSO₄ N-甲基吗啉 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 tert-butyl (6S,7S)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-7-carboxylate
  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
• 作为产物：
  描述：

  L-天门冬氨酸-4-叔丁基酯 在 potassium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium iodide 、 potassium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醚 、 水 、 丙酮 、 甲苯 、 乙腈 为溶剂， 反应 51.5h， 生成 5,6-dibenzyl 7-tert-butyl (6S,7S)-5-azaspiro[2.5]octane-5,6,7-tricarboxylate
  参考文献：
  名称：

  AZA SPIRO ALKANE DERIVATIVES AS INHIBITORS OF METALLPROTEASES

  摘要：

  公开号：

  EP1622569B1

文献信息

• Asymmetric Synthesis of Conformationally Constrained <i>trans</i>-2,3-Piperidinedicarboxylic Acid Derivatives
  作者：Jincong Zhuo、Wenqing Yao、David Burns、Colin Zhang、Meizhong Xu、Lingkai Weng、Ding-Quan Qian、Chunhong He、Qiyan Lin、Yun-Long Li、Eric Shi、Costas Agrios、Brian Metcalf

  DOI：10.1055/s-2007-968029

  日期：2007.2

  An efficient asymmetric synthesis of conformationally constrained (2S,3S)-piperidinedicarboxylic acid derivatives starting from L-aspartic acid β-tert-butyl ester and 3-chloro-2-(chloromethyl)-1-propene is described. The key steps involve N-alkylation of the aspartic acid ester followed by a stereoselective enolate intramolecular cyclization (>95:5 dr). Various synthetic strategies were explored to

  描述了从 L-天冬氨酸 β-叔丁酯和 3-氯-2-(氯甲基)-1-丙烯开始的构象约束 (2S,3S)-哌啶二羧酸衍生物的有效不对称合成。关键步骤包括天冬氨酸酯的 N-烷基化，然后是立体选择性烯醇分子内环化 (>95:5 dr)。探索了各种合成策略以实现所得烯烃的环丙烷化，包括 Simmons-Smith 反应和钯催化的环丙烷化。
• Aza spiro alkane derivatives as inhibitors of metalloproteases
  申请人：——

  公开号：US20040259896A1

  公开（公告）日：2004-12-23

  The present invention provides a compound of Formula I or Formula II: 1 enantiomer, diastereomer, prodrug, solvate, metabolite, or pharmaceutically acceptable salt thereof, wherein constituent variables are provided herein. The compounds of Formula I and II are modulators of metalloproteases and are useful in treating diseases associated with metalloprotease activity such as arthritis, cancer, cardiovascular disorders, skin disorders, inflammation and allergic conditions.

  本发明提供了公式I或公式II的化合物：1对映异构体，对映体，前药，溶剂化物，代谢物或其药学上可接受的盐，其中组分变量在此处提供。公式I和II的化合物是金属蛋白酶调节剂，可用于治疗与金属蛋白酶活性相关的疾病，如关节炎，癌症，心血管疾病，皮肤疾病，炎症和过敏症。
• AZA SPIRO ALKANE DERIVATIVES AS INHIBITORS OF METALLOPROTEASES
  申请人：Yao Wenqing

  公开号：US20090124649A1

  公开（公告）日：2009-05-14

  The present invention provides a compound of Formula I or Formula II: enantiomer, diastereomer, prodrug, solvate, metabolite, or pharmaceutically acceptable salt thereof, wherein constituent variables are provided herein. The compounds of Formula I and II are modulators of metalloproteases and are useful in treating diseases associated with metalloprotease activity such as arthritis, cancer, cardiovascular disorders, skin disorders, inflammation and allergic conditions.

  本发明提供了I式或II式的化合物：其对映异构体、顺反异构体、前药、溶剂化物、代谢物或其药学上可接受的盐，其中所述的组分变量已在此处提供。I和II式的化合物是金属蛋白酶的调节剂，并且在治疗与金属蛋白酶活性相关的疾病，例如关节炎、癌症、心血管疾病、皮肤疾病、炎症和过敏症方面很有用。
• AZA SPIRO ALKANE DERIVATIVES AS INHIBITORS OF METALLOPROTEASES
  申请人：Yao Wenqing

  公开号：US20110288068A1

  公开（公告）日：2011-11-24

  The present invention provides a compound of Formula I or Formula II: enantiomer, diastereomer, prodrug, solvate, metabolite, or pharmaceutically acceptable salt thereof, wherein constituent variables are provided herein. The compounds of Formula I and II are modulators of metalloproteases and are useful in treating diseases associated with metalloprotease activity such as arthritis, cancer, cardiovascular disorders, skin disorders, inflammation and allergic conditions.

  本发明提供了化合物I或化合物II的化合物：对映体、顺反异构体、前药、溶剂化物、代谢物或其药学上可接受的盐，其中组成变量在此处提供。化合物I和II是金属蛋白酶调节剂，可用于治疗与金属蛋白酶活性相关的疾病，如关节炎、癌症、心血管疾病、皮肤疾病、炎症和过敏症。
• AZA Spiro Alkane Derivatives as Inhibitors of Metalloproteases
  申请人：INCYTE CORPORATION

  公开号：US20140187530A1

  公开（公告）日：2014-07-03

  The present invention provides a compound of Formula I or Formula II: enantiomer, diastereomer, prodrug, solvate, metabolite, or pharmaceutically acceptable salt thereof, wherein constituent variables are provided herein. The compounds of Formula I and II are modulators of metalloproteases and are useful in treating diseases associated with metalloprotease activity such as arthritis, cancer, cardiovascular disorders, skin disorders, inflammation and allergic conditions.

  本发明提供公式I或公式II的化合物：其对映体，顺反异构体，前药，溶剂化物，代谢物或其药学上可接受的盐，其中组成变量在此提供。公式I和II的化合物是金属蛋白酶调节剂，并且在治疗与金属蛋白酶活性相关的疾病，例如关节炎，癌症，心血管疾病，皮肤疾病，炎症和过敏症方面是有用的。