α-(S)-methyl-β-alanine benzyl ester hydrochloride | 1345219-34-2

• 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: α-(S)-methyl-β-alanine benzyl ester hydrochloride
• 英文别名: benzyl (2S)-3-amino-2-methylpropanoate;hydrochloride
• CAS: 1345219-34-2
• 化学式: C₁₁H₁₅NO₂*ClH
• 分子量: 229.707
• InChiKey: XTKGXIHXCKBKSN-FVGYRXGTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.75
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  52.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  α-(S)-methyl-β-alanine benzyl ester hydrochloride 在 N-甲基吗啉 、 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 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 103.0h， 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：

  N-(tert-butoxycarbonyl)-α-(S)-methyl-β-alanine benzyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以92%的产率得到α-(S)-methyl-β-alanine benzyl ester hydrochloride
  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

• Phosphorous containing compounds as inhibitors of enkephalinases
  申请人：SCHERING CORPORATION

  公开号：EP0117429A1

  公开（公告）日：1984-09-05

  Compounds having the general formula in which W is R' or OR', R' being hydrogen, alkyl, phenyl or benzyl Xis-(CH2)P-CHR3 or CHR3-(CH2)p- R33 is chosen from various substituents, or Z is chosen from various of organic groups, and R2 forms, with the carbonyl group to which it is attached, carboxy or various esterified carboxy groups or is the group -NR8R9. The compounds inhibit the activity of enkephalinases. Intermediates of formula are disclosed in which Wa is alkoxy, phenoxy or benzyloxy Xa is CH2CH-, and Ya is -NH2 or -NCO.

  具有通式的化合物，其中 W 是 R'或 OR'，R'是氢、烷基、苯基或苄基，Xis-(CH2)P-CHR3 或 CHR3-(CH2)p- R33 可从各种取代基中选择，或 Z 可从各种有机基团中选择，R2 与所连接的羰基形成羧基或各种酯化羧基，或为基团 -NR8R9。 这些化合物可抑制脑啡肽酶的活性。 公开了式中的中间体，其中 Wa 是烷氧基、苯氧基或苄氧基，Xa 是 CH2CH-，Ya 是 -NH2 或 -NCO。
• 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.