(2R,3R), 3-benzyloxycarbonylamino-2-[4-methoxybenzylsulfanyl]-hex-4-ene-1,6-dioic acid 6-benzyl ester 1-tertiobutyl ester | 263552-45-0

• 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: (2R,3R), 3-benzyloxycarbonylamino-2-[4-methoxybenzylsulfanyl]-hex-4-ene-1,6-dioic acid 6-benzyl ester 1-tertiobutyl ester
• 英文别名: 1-O-benzyl 6-O-tert-butyl (E,4R,5R)-5-[(4-methoxyphenyl)methylsulfanyl]-4-(phenylmethoxycarbonylamino)hex-2-enedioate
• CAS: 263552-45-0
• 化学式: C₃₃H₃₇NO₇S
• 分子量: 591.725
• InChiKey: YQBCAGMICRRDAX-FMXUKPFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  42
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 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), 3-benzyloxycarbonylamino-2-[4-methoxybenzylsulfanyl]-hex-4-ene-1,6-dioic acid 6-benzyl ester 1-tertiobutyl ester 在 Stryker's reagent 作用下， 反应 3.0h， 以87%的产率得到(2RS,3R), 3-benzyloxycarbonylamino-2-[4-methoxybenzylsulfanyl]-hexan-1,6-dioic acid 6-benzyl ester 1-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
• 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， 以 四氢呋喃 、 正己烷 为溶剂， 反应 4.5h， 生成 (2R,3R), 3-benzyloxycarbonylamino-2-[4-methoxybenzylsulfanyl]-hex-4-ene-1,6-dioic acid 6-benzyl ester 1-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