N-[1-(S)-carboxy-3-phenylpropyl]-L-4,4'-biphenylalanyl-β-alanine | 1345219-20-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: N-[1-(S)-carboxy-3-phenylpropyl]-L-4,4'-biphenylalanyl-β-alanine
• 英文别名: (2S)-2-[[(2S)-1-(2-carboxyethylamino)-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]-4-phenylbutanoic acid
• CAS: 1345219-20-6
• 化学式: C₂₈H₃₀N₂O₅
• 分子量: 474.557
• InChiKey: XIRVOOJFZHUHPR-DQEYMECFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  L-4,4'-biphenylalanyl-β-alanine benzyl ester formate 在 三氟甲磺酸酐 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 110.5h， 生成 N-[1-(S)-carboxy-3-phenylpropyl]-L-4,4'-biphenylalanyl-β-alanine
  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

文献信息

• Structure-based design of dipeptide derivatives for the human neutral endopeptidase
  作者：Kensuke Misawa、Yasuto Suzuki、Satoshi Takahashi、Atsushi Yoshimori、Ryoko Takasawa、Yusuke Shibuya、Sei-ichi Tanuma

  DOI：10.1016/j.bmc.2011.08.064

  日期：2011.10

  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.