(E)-6-benzyloxycarbonylamino-4-tert-butoxycarbonylamino-hex-2-enoic acid ethyl ester | 197892-28-7

• 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: (E)-6-benzyloxycarbonylamino-4-tert-butoxycarbonylamino-hex-2-enoic acid ethyl ester
• 英文别名: 6-Benzyloxycarbonylamino-4S-tert-butoxycarbonylamino-hex-2E-enoic acid ethyl ester；6-Benzyloxycarbonylamino-4-tert-butoxycarbonylamino-hex-2E-enoic acid ethyl ester；ethyl (E)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-6-(phenylmethoxycarbonylamino)hex-2-enoate
• CAS: 197892-28-7
• 化学式: C₂₁H₃₀N₂O₆
• 分子量: 406.479
• InChiKey: GLPQBIANUPQKRH-VAWYXSNFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  29
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-6-benzyloxycarbonylamino-4-tert-butoxycarbonylamino-hex-2-enoic acid ethyl ester 在 N,N-二甲基丙烯基脲 、 四甲基乙二胺 、 叔丁基氯化镁 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 为溶剂， 反应 22.83h， 生成 rel-(3aS,6S,6aR)-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
• 作为产物：
  描述：

  H-A2bu(Z)-OH 在 N-甲基吗啉 、 sodium hydroxide 、 sodium tetrahydroborate 、 草酰氯 、 二甲基亚砜 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 24.13h， 生成 (E)-6-benzyloxycarbonylamino-4-tert-butoxycarbonylamino-hex-2-enoic acid ethyl 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

• [EN] PYRROLOPYRROLONE DERIVATIVES AS INHIBITORS OF NEUTROPHIL ELASTASE<br/>[FR] DERIVES DU PYRROLOPYRROLONE UTILISES COMME INHIBITEURS DE L'ELASTASE DE NEUTROPHILES
  申请人：GLAXO GROUP LIMITED

  公开号：WO1997036903A1

  公开（公告）日：1997-10-09

  (EN) There are described according to the invention compounds of formula (I) (relative stereochemistry indicated), wherein R1, R2, R3 and X are as defined in the specification, together with processes for preparing them, compositions containing them and their use as pharmaceuticals. Compounds of formula (I) are indicated $i(inter alia) for the treatment of chronic bronchitis.(FR) L'invention concerne des composés selon la formule (I) (stéréochimie relative indiquée). Dans la formule, R1, R2, R3 et X sont comme définis dans le descriptif. L'invention traite également de procédés pour préparer ces composés, de compositions les contenant et de leur utilisation comme produits pharmaceutiques. Les composés de la formule (I) sont indiqués, entre autres, pour le traitement de la bronchite chronique.

  根据本发明，描述了公式（I）（相对立体化学指示）的化合物，其中R1、R2、R3和X如规范中定义，以及制备它们的过程，包含它们的组合物和它们作为药物的用途。公式（I）的化合物被指示用于治疗慢性支气管炎，其中R1、R2、R3和X在规范中定义。
• Borthwick, Alan D.; Crame, Andrew J.; Davies, David E., Synlett, 2000, # 4, p. 504 - 508
  作者：Borthwick, Alan D.、Crame, Andrew J.、Davies, David E.、Exall, Anne M.、Jackson, Deborah L.、Mason, Andrew M.、Pennell, Andrew M. K.、Weingarten, Gordon G.

  DOI：——

  日期：——
• PYRROLOPYRROLONE DERIVATIVES AS INHIBITORS OF NEUTROPHIL ELASTASE
  申请人：GLAXO GROUP LIMITED

  公开号：EP0891362B1

  公开（公告）日：2004-03-17
• US5994344A
  申请人：——

  公开号：US5994344A

  公开（公告）日：1999-11-30
• US6057457A
  申请人：——

  公开号：US6057457A

  公开（公告）日：2000-05-02