4-<(methoxysuccinyl)-L-alanyl-L-alanyl-L-prolinamido>phenyl N,N-dimethylcarbamate | 92279-28-2

• 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: 4-<(methoxysuccinyl)-L-alanyl-L-alanyl-L-prolinamido>phenyl N,N-dimethylcarbamate
• 英文别名: 4-[(methoxysuccinyl)-L-alanyl-L-alanyl-L-prolinamido]phenyl N,N-dimethylcarbamate；methyl 4-[[(2S)-1-[[(2S)-1-[(2S)-2-[[4-(dimethylcarbamoyloxy)phenyl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoate
• CAS: 92279-28-2
• 化学式: C₂₅H₃₅N₅O₈
• 分子量: 533.582
• InChiKey: KIAVILZUFQNYLD-BXWFABGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  38
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  163
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  succinic acid 2,5-dioxo-pyrrolidin-1-yl ester methyl ester 在 N-甲基吗啉 、 碳酸氢钠 、 牛血清白蛋白 、 氯甲酸异丁酯 作用下， 以 水 、 丙酮 为溶剂， 反应 4.5h， 生成 4-<(methoxysuccinyl)-L-alanyl-L-alanyl-L-prolinamido>phenyl N,N-dimethylcarbamate
  参考文献：
  名称：

  Peptidyl carbamates incorporating amino acid isosteres as novel elastase inhibitors

  摘要：

  The design and synthesis of 13 novel peptidyl carbamates are described. When tested for inhibitory activity toward porcine pancreatic elastase, trypsin, and chymotrypsin, six compounds were found to specifically inhibit elastase without affecting the other two serine proteases. All the active inhibitors had an amino acid isostere at the P1 position. Kinetic studies indicated that the inhibition was competitive with Ki values ranging from 4.23 X 10(-5) to 2.4 X 10(-6) M. The degree of inhibition was found to be dependent on the specificity of the peptide chain for the extended subsites on the enzyme as well as on the nature of P1'. Preliminary work on one inhibitor indicates that the inhibition is reversible and proceeds via the rapid formation of a strong enzyme-inhibitor complex, followed by slow acylation of the serine residue on the active site of the enzyme. Peptidyl carbamates represent a novel class of elastase inhibitors.

  DOI：

  10.1021/jm00158a025

文献信息

• INHIBITORS OF IAPS
  申请人：Dudley Danette

  公开号：US20110269696A1

  公开（公告）日：2011-11-03

  The invention provides novel compounds that are inhibitors of IAPs having the general formula: wherein X 1 , X 2 , X 3 , Y, A, R 1 , R 2 , R 3 , R 4 , R 4′ , R 5 , R 5′ , R 6 and R 6′ are as described herein. The compouds of the invention may be used to induce apoptosis in cells (or sensitise cells to apoptosis) in which IAPs are overexpressed or otherwise implicated in resistance to normal apoptotic processes. Accordingly, the compounds may be provided in pharmaceutically acceptable compositions and used for the treatment cancers.

  该发明提供了一种通式为以下的IAPs抑制剂新化合物：其中X1、X2、X3、Y、A、R1、R2、R3、R4、R4′、R5、R5′、R6和R6′如本文所述。该发明的化合物可用于在IAPs过度表达或以其他方式涉及对正常凋亡过程的抵抗的细胞中诱导凋亡（或使细胞对凋亡敏感）。因此，这些化合物可以与药物适用的组成物一起提供，并用于治疗癌症。
• US8835393B2
  申请人：——

  公开号：US8835393B2

  公开（公告）日：2014-09-16
• Peptidyl carbamates incorporating amino acid isosteres as novel elastase inhibitors
  作者：George A. Digenis、Bushra J. Agha、Kiyoshi Tsuji、Masayuki Kato、Masaki Shinogi

  DOI：10.1021/jm00158a025

  日期：1986.8

  The design and synthesis of 13 novel peptidyl carbamates are described. When tested for inhibitory activity toward porcine pancreatic elastase, trypsin, and chymotrypsin, six compounds were found to specifically inhibit elastase without affecting the other two serine proteases. All the active inhibitors had an amino acid isostere at the P1 position. Kinetic studies indicated that the inhibition was competitive with Ki values ranging from 4.23 X 10(-5) to 2.4 X 10(-6) M. The degree of inhibition was found to be dependent on the specificity of the peptide chain for the extended subsites on the enzyme as well as on the nature of P1'. Preliminary work on one inhibitor indicates that the inhibition is reversible and proceeds via the rapid formation of a strong enzyme-inhibitor complex, followed by slow acylation of the serine residue on the active site of the enzyme. Peptidyl carbamates represent a novel class of elastase inhibitors.