4-O-[(E)-[amino(phenyl)methylidene]amino] 1-O-benzyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanedioate | 220050-46-4

• 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: 4-O-[(E)-[amino(phenyl)methylidene]amino] 1-O-benzyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanedioate
• CAS: 220050-46-4
• 化学式: C₂₃H₂₇N₃O₆
• 分子量: 441.484
• InChiKey: MATNQCNHVZJXTB-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  129
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-O-[(E)-[amino(phenyl)methylidene]amino] 1-O-benzyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanedioate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (2S)-2-amino-3-(3-phenyl-[1,2,4]oxadiazol-5-yl)-propionic acid benzyl ester
  参考文献：
  名称：

  Synthesis and evaluation of heteroarylalanine diacids as potent and selective neutral endopeptidase inhibitors

  摘要：

  Heteroarylalanine derivatives 4 were designed as potential inhibitors of neutral endopeptidase (NEP EC 3.4.24.11). Selectivity over other zinc metalloproteinases was explored through occupation of the S2' sub-site within NEP. Structural optimisation led to the identification of 5-phenyl oxazole 4f, a potent and selective NEP inhibitor. A crystal structure of the inhibitor bound complex is reported. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.109
• 作为产物：
  描述：

  Boc-L-天冬氨酸 1-苄酯 、 苯甲酰胺肟 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以30%的产率得到4-O-[(E)-[amino(phenyl)methylidene]amino] 1-O-benzyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanedioate
  参考文献：
  名称：

  Synthesis and evaluation of heteroarylalanine diacids as potent and selective neutral endopeptidase inhibitors

  摘要：

  Heteroarylalanine derivatives 4 were designed as potential inhibitors of neutral endopeptidase (NEP EC 3.4.24.11). Selectivity over other zinc metalloproteinases was explored through occupation of the S2' sub-site within NEP. Structural optimisation led to the identification of 5-phenyl oxazole 4f, a potent and selective NEP inhibitor. A crystal structure of the inhibitor bound complex is reported. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.109

文献信息

• [EN] CYCLOPENTYL GLUTARAMIDES AND THEIR USE AS NEUTRAL ENDOPEPTIDASE INHIBITORS<br/>[FR] GLUTARAMIDES CYCLOPENTYLE ET UTILISATION DE CES COMPOSES COMME INHIBITEURS D'ENDOPEPTIDASE NEUTRE (NEP)
  申请人：PFIZER LTD

  公开号：WO2004056787A1

  公开（公告）日：2004-07-08

  The invention relates to NEP inhibitors for treating cardiovascular disorders wherein R1 is C1-C6alkyl, C1-C6alkoxyC1-C3alkyl or C1-C6alkoxyC1-C6alkoxyC,-C3alkyl; R2 is hydrogen or C1-C6alkyl; L is an aromatic heterocyclic ring, optionally substituted with C,­ C6alkyl or halo; R3 is C1-C6alkyl optionally substituted by halo, alkoxy, haloalkoxy, alkylthio, haloalkylthio or nitrile group, or R3 is phenyl or aromatic heterocyclyl each of which may be independently substituted by one or more alkyl, halo, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio or nitrile group; R4 and R5 are either both hydrogen, or one of R4 and R5 is hydrogen and the other is a biolabile ester-forming group that in the body of a patient is replaced by hydrogen; p is 0, 1 or 2; and q is 1 or 2.

  该发明涉及NEP抑制剂，用于治疗心血管疾病，其中R1为C1-C6烷基，C1-C6烷氧基C1-C3烷基或C1-C6烷氧基C1-C6烷氧基，R2为氢或C1-C6烷基，L为芳香杂环环，可选择性地取代为C，C6烷基或卤素，R3为C1-C6烷基，可选择性地取代为卤素，烷氧基，卤代烷氧基，烷基硫醚，卤代烷基硫醚或腈基，或R3为苯基或芳香杂环基，每个基团可独立地取代为一个或多个烷基，卤素，卤代烷基，烷氧基，卤代烷氧基，烷基硫醚，卤代烷基硫醚或腈基；R4和R5要么都是氢，要么R4和R5中的一个是氢，另一个是在患者体内被氢取代的生物易降解酯基团；p为0、1或2；q为1或2。
• Synthesis and evaluation of heteroarylalanine diacids as potent and selective neutral endopeptidase inhibitors
  作者：Melanie S. Glossop、Richard J. Bazin、Kevin N. Dack、David N.A. Fox、Graeme A. MacDonald、Mark Mills、Dafydd R. Owen、Chris Phillips、Keith A. Reeves、Tracy J. Ringer、Ross S. Strang、Christine A.L. Watson

  DOI：10.1016/j.bmcl.2011.03.109

  日期：2011.6

  Heteroarylalanine derivatives 4 were designed as potential inhibitors of neutral endopeptidase (NEP EC 3.4.24.11). Selectivity over other zinc metalloproteinases was explored through occupation of the S2' sub-site within NEP. Structural optimisation led to the identification of 5-phenyl oxazole 4f, a potent and selective NEP inhibitor. A crystal structure of the inhibitor bound complex is reported. (C) 2011 Elsevier Ltd. All rights reserved.