(2R,3R), 2-benzyloxycarbonylamino, 3-(4-methoxybenzylsulfanyl)-succinic acid 1-methyl ester 4-tertiobutyl ester | 263552-35-8

• 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: (2R,3R), 2-benzyloxycarbonylamino, 3-(4-methoxybenzylsulfanyl)-succinic acid 1-methyl ester 4-tertiobutyl ester
• 英文别名: 4-O-tert-butyl 1-O-methyl (2R,3R)-3-[(4-methoxyphenyl)methylsulfanyl]-2-(phenylmethoxycarbonylamino)butanedioate
• CAS: 263552-35-8
• 化学式: C₂₅H₃₁NO₇S
• 分子量: 489.59
• InChiKey: YQZXEOGHQFCCAN-LEWJYISDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  34
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R,3R), 2-benzyloxycarbonylamino, 3-(4-methoxybenzylsulfanyl)-succinic acid 1-methyl ester 4-tertiobutyl ester 在 正丁基锂 、 Stryker's reagent 、 三氟乙酸 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 7.5h， 生成 (2RS,3R), 3-benzyloxycarbonylamino-2-[4-methoxybenzylsulfanyl]-5-[dibenzyloxyphosphoryl]-pentanoic acid
  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：

  N-苄氧羰基-L-天门冬氨酸 4-叔丁酯 在 正丁基锂 作用下， 生成 (2R,3R), 2-benzyloxycarbonylamino, 3-(4-methoxybenzylsulfanyl)-succinic acid 1-methyl ester 4-tertiobutyl 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.