N-(tert-butoxycarbonyl)-α-(S)-methyl-β-alanine benzyl ester | 1345219-32-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(tert-butoxycarbonyl)-α-(S)-methyl-β-alanine benzyl ester
• 英文别名: benzyl (2S)-2-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 1345219-32-0
• 化学式: C₁₆H₂₃NO₄
• 分子量: 293.363
• InChiKey: AMXWNZWGCCTFEK-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(tert-butoxycarbonyl)-α-(S)-methyl-β-alanine benzyl ester 在 N-甲基吗啉 、 盐酸 、 三氟甲磺酸酐 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 104.0h， 生成 N-[1-(S)-benzyloxycarbonyl-3-phenylpropyl]-L-4,4'-biphenylalanyl-α-(S)-methyl-β-alanine benzyl ester
  参考文献：
  名称：

  Structure-based design of dipeptide derivatives for the human neutral endopeptidase

  摘要：

  Neutral endopeptidase (NEP) plays a key role in the metabolic inactivation of various bioactive peptides such as atrial natriuretic peptide (ANP), endothelins, and enkephalins. Furthermore, NEP is known to work as elastase in skin fibroblast. Therefore, effective inhibitors of NEP offer significant therapeutic interest as antihypertensives, analgesics, and skin anti-aging agents. Recently, the X-ray crystal structure of human NEP complexed with phosphoramidon has been reported and provided insights into the active site specificity of NEP. Here, we designed new inhibitors by using in silico molecular modeling and synthesized them by short steps. Expectedly, we found highly effective inhibitors with sub-nanomolar levels of IC(50) values. These results indicate that our structure-based molecular designing program is useful for obtaining novel NEP inhibitors. Furthermore, these inhibitors may be attractive leads for the generation of new pharmaceuticals for NEP-related diseases. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.064
• 作为产物：
  描述：

  (S)-3-(叔丁氧羰基氨基)-2-甲基丙酸 、 苯甲醇 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 氯仿 为溶剂， 反应 6.0h， 以98%的产率得到N-(tert-butoxycarbonyl)-α-(S)-methyl-β-alanine benzyl ester
  参考文献：
  名称：

  Structure-based design of dipeptide derivatives for the human neutral endopeptidase

  摘要：

  Neutral endopeptidase (NEP) plays a key role in the metabolic inactivation of various bioactive peptides such as atrial natriuretic peptide (ANP), endothelins, and enkephalins. Furthermore, NEP is known to work as elastase in skin fibroblast. Therefore, effective inhibitors of NEP offer significant therapeutic interest as antihypertensives, analgesics, and skin anti-aging agents. Recently, the X-ray crystal structure of human NEP complexed with phosphoramidon has been reported and provided insights into the active site specificity of NEP. Here, we designed new inhibitors by using in silico molecular modeling and synthesized them by short steps. Expectedly, we found highly effective inhibitors with sub-nanomolar levels of IC(50) values. These results indicate that our structure-based molecular designing program is useful for obtaining novel NEP inhibitors. Furthermore, these inhibitors may be attractive leads for the generation of new pharmaceuticals for NEP-related diseases. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.064