(2S)-(benzyloxycarbonylamino)-4-chlorosulfonyl-butyric acid methyl ester | 255737-47-4

• 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: (2S)-(benzyloxycarbonylamino)-4-chlorosulfonyl-butyric acid methyl ester
• 英文别名: methyl (2S)-2-{[(benzyloxy)carbonyl]amino}-4-sulfobutanoate；methyl (2S)-4-chlorosulfonyl-2-(phenylmethoxycarbonylamino)butanoate
• CAS: 255737-47-4
• 化学式: C₁₃H₁₆ClNO₆S
• 分子量: 349.792
• InChiKey: YSKBVJKRWRMIFH-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S)-(benzyloxycarbonylamino)-4-chlorosulfonyl-butyric acid methyl ester 在 N-甲基吗啉 、 吡啶 、 sodium hydroxide 、 silver benzoate 、 三乙胺 作用下， 生成 (3RS), 3-benzyloxycarbonylamino, 5-neopentyloxysulfonyl-pentanoic acid methyl ester
  参考文献：
  名称：

  Investigation of Subsite Preferences in Aminopeptidase A (EC 3.4.11.7) Led to the Design of the First Highly Potent and Selective Inhibitors of This Enzyme

  摘要：

  The study of the physiological roles of the membrane-bound zinc-aminopeptidase A (glutamyl aminopeptidase, EC 3.4.11.7) needs the design of efficient and selective inhibitors of this enzyme. An acute exploration of aminopeptidase A active site was performed by a combinatorial approach using (3-amino-2-mercapto-acyl)dipeptides able to sc its S-1, S-1', and S-2' subsites. This analysis confirmed that the S-1 subsite is optimally blocked by a glutamate or isosteric residues and demonstrated that the S-1' subsite is hydrophobic whereas the S-2' subsite recognizes preferentially negatively charged residues derived from aspartic acid. The optimization of these structural parameters led to the synthesis of nanomolar and subnanomolar inhibitors of aminopeptidase A such as H3N+CH(CH2CH2SO3-)CH(SH)CO-Ile-(3-COOH)Pro that exhibits a K-i of 0.87 nM. The best compounds were synthesized by a stereochemically controlled route. These first described highly potent inhibitors could allow studies about the role of physiological substrates of APA such as angiotensin II- and cholecystokinin CCK8 in the central nervous system.

  DOI：

  10.1021/jm9903040
• 作为产物：
  描述：

  dimethyl bis(N-benzyloxycarbonyl)-L-homocystine 在 甲醇 、 氯 作用下， 以 四氯化碳 为溶剂， 以100%的产率得到(2S)-(benzyloxycarbonylamino)-4-chlorosulfonyl-butyric acid methyl ester
  参考文献：
  名称：

  Investigation of Subsite Preferences in Aminopeptidase A (EC 3.4.11.7) Led to the Design of the First Highly Potent and Selective Inhibitors of This Enzyme

  摘要：

  The study of the physiological roles of the membrane-bound zinc-aminopeptidase A (glutamyl aminopeptidase, EC 3.4.11.7) needs the design of efficient and selective inhibitors of this enzyme. An acute exploration of aminopeptidase A active site was performed by a combinatorial approach using (3-amino-2-mercapto-acyl)dipeptides able to sc its S-1, S-1', and S-2' subsites. This analysis confirmed that the S-1 subsite is optimally blocked by a glutamate or isosteric residues and demonstrated that the S-1' subsite is hydrophobic whereas the S-2' subsite recognizes preferentially negatively charged residues derived from aspartic acid. The optimization of these structural parameters led to the synthesis of nanomolar and subnanomolar inhibitors of aminopeptidase A such as H3N+CH(CH2CH2SO3-)CH(SH)CO-Ile-(3-COOH)Pro that exhibits a K-i of 0.87 nM. The best compounds were synthesized by a stereochemically controlled route. These first described highly potent inhibitors could allow studies about the role of physiological substrates of APA such as angiotensin II- and cholecystokinin CCK8 in the central nervous system.

  DOI：

  10.1021/jm9903040

文献信息

• Investigation of Subsite Preferences in Aminopeptidase A (EC 3.4.11.7) Led to the Design of the First Highly Potent and Selective Inhibitors of This Enzyme
  作者：Christelle David、Laurent Bischoff、Hervé Meudal、Aurélie Mothé、Nadia De Mota、Sophie DaNascimento、Catherine Llorens-Cortes、Marie-Claude Fournié-Zaluski、Bernard P. Roques

  DOI：10.1021/jm9903040

  日期：1999.12.1

  The study of the physiological roles of the membrane-bound zinc-aminopeptidase A (glutamyl aminopeptidase, EC 3.4.11.7) needs the design of efficient and selective inhibitors of this enzyme. An acute exploration of aminopeptidase A active site was performed by a combinatorial approach using (3-amino-2-mercapto-acyl)dipeptides able to sc its S-1, S-1', and S-2' subsites. This analysis confirmed that the S-1 subsite is optimally blocked by a glutamate or isosteric residues and demonstrated that the S-1' subsite is hydrophobic whereas the S-2' subsite recognizes preferentially negatively charged residues derived from aspartic acid. The optimization of these structural parameters led to the synthesis of nanomolar and subnanomolar inhibitors of aminopeptidase A such as H3N+CH(CH2CH2SO3-)CH(SH)CO-Ile-(3-COOH)Pro that exhibits a K-i of 0.87 nM. The best compounds were synthesized by a stereochemically controlled route. These first described highly potent inhibitors could allow studies about the role of physiological substrates of APA such as angiotensin II- and cholecystokinin CCK8 in the central nervous system.