rel-(3aS,6S,6aR)-4-methanesulfonyl-6-methyl-5-oxo-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl ester

• 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: rel-(3aS,6S,6aR)-4-methanesulfonyl-6-methyl-5-oxo-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl ester
• 英文别名: benzyl (3aS,6S,6aR)-6-methyl-4-methylsulfonyl-5-oxo-3,3a,6,6a-tetrahydro-2H-pyrrolo[3,2-b]pyrrole-1-carboxylate
• 化学式: C₁₆H₂₀N₂O₅S
• 分子量: 352.411
• InChiKey: FCHBDSWTEKROAB-FPMFFAJLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  92.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  H-A2bu(Z)-OH 在 N-甲基吗啉 、 N,N-二甲基丙烯基脲 、 sodium hydroxide 、 sodium tetrahydroborate 、 草酰氯 、 四甲基乙二胺 、 2-氯-1-甲基吡啶碘化物 、 二甲基亚砜 、 三乙胺 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 114.63h， 生成 rel-(3aS,6S,6aR)-4-methanesulfonyl-6-methyl-5-oxo-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl ester
  参考文献：
  名称：

  Design and Synthesis of Pyrrolidine-5,5-trans-lactams (5-Oxo-hexahydro-pyrrolo[3,2-b]pyrroles) as Novel Mechanism-Based Inhibitors of Human Cytomegalovirus Protease. 1. The α-Methyl-trans-lactam Template

  摘要：

  Mechanism-based inhibitors of human cytomegalovirus (HCMV) protease have been designed based on the pyrrolidine-5,5-trans-lactam ring system. New routes to the beta -methyl-, desmethyl-, and alpha -methyl-pyrrolidine-5,5-trans-lactam templates have been developed from 2,4-diaminobutyric acid. ESI/MS studies have shown that these inhibitors can bind covalently and reversibly to the viral enzyme in a time-dependent manner by a mechanism which is consistent; with acylation of HCMV delta Ala protease at the active site nucleophile Ser 132. SAR in this series of pyrrolidine-5,5-trans-lactams has defined the relative stereochemisty of the methyl substituent adjacent to the lactam carbonyl, the functionality on the lactam nitrogen, and the mechanism of action of this novel series of serine protease inhibitors against the HCMV dAla protease. Activity decreases on moving from the alpha -methyl to the desmethyl to the beta -methyl series. This selectivity is the opposite of that observed for these templates against the elastase and thrombin enzymes. The activity against HCMV delta Ala protease is the greatest with inhibitors based on the Cbz-protected alpha -methyl-5,5-trans-lactam template which have low micromolar activity against the viral enzyme.

  DOI：

  10.1021/jm000078q

文献信息

• Design and Synthesis of Pyrrolidine-5,5-<i>trans-</i>lactams (5-Oxo-hexahydro-pyrrolo[3,2-<i>b</i>]pyrroles) as Novel Mechanism-Based Inhibitors of Human Cytomegalovirus Protease. 1. The α-Methyl-<i>trans</i>-lactam Template
  作者：Alan D. Borthwick、S. Jane Angier、Andrew J. Crame、Anne M. Exall、Terry M. Haley、Graham J. Hart、Andrew M. Mason、Andrew M. K. Pennell、Gordon G. Weingarten

  DOI：10.1021/jm000078q

  日期：2000.11.1

  Mechanism-based inhibitors of human cytomegalovirus (HCMV) protease have been designed based on the pyrrolidine-5,5-trans-lactam ring system. New routes to the beta -methyl-, desmethyl-, and alpha -methyl-pyrrolidine-5,5-trans-lactam templates have been developed from 2,4-diaminobutyric acid. ESI/MS studies have shown that these inhibitors can bind covalently and reversibly to the viral enzyme in a time-dependent manner by a mechanism which is consistent; with acylation of HCMV delta Ala protease at the active site nucleophile Ser 132. SAR in this series of pyrrolidine-5,5-trans-lactams has defined the relative stereochemisty of the methyl substituent adjacent to the lactam carbonyl, the functionality on the lactam nitrogen, and the mechanism of action of this novel series of serine protease inhibitors against the HCMV dAla protease. Activity decreases on moving from the alpha -methyl to the desmethyl to the beta -methyl series. This selectivity is the opposite of that observed for these templates against the elastase and thrombin enzymes. The activity against HCMV delta Ala protease is the greatest with inhibitors based on the Cbz-protected alpha -methyl-5,5-trans-lactam template which have low micromolar activity against the viral enzyme.