(2S)-2-(benzyloxycarbonylamino)-N-(3-(((R)-1-hydroxy)-2-(((1S)-1-benzyl-2-hydroxyethyl)(tert-butoxycarbonylamino))ethyl)phenyl)-2-phenylacetamide

• 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: (2S)-2-(benzyloxycarbonylamino)-N-(3-(((R)-1-hydroxy)-2-(((1S)-1-benzyl-2-hydroxyethyl)(tert-butoxycarbonylamino))ethyl)phenyl)-2-phenylacetamide
• 英文别名: tert-butyl N-[(2R)-2-hydroxy-2-[3-[[(2S)-2-phenyl-2-(phenylmethoxycarbonylamino)acetyl]amino]phenyl]ethyl]-N-[(2S)-1-hydroxy-3-phenylpropan-2-yl]carbamate
• 化学式: C₃₈H₄₃N₃O₇
• 分子量: 653.775
• InChiKey: FLEBPNFYCLAFSM-AFEGWXKPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  48
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  137
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S)-2-(benzyloxycarbonylamino)-N-(3-(((R)-1-hydroxy)-2-(((1S)-1-benzyl-2-hydroxyethyl)(tert-butoxycarbonylamino))ethyl)phenyl)-2-phenylacetamide 在 盐酸 、 乙酰氯 作用下， 以 甲醇 为溶剂， 以99%的产率得到(2S)-2-(benzyloxycarbonylamino)-N-(3-(((R)-1-hydroxy)-2-((1S)-1-benzyl-2-hydroxyethyl)aminoethyl)phenyl)-2-phenylacetamide hydrochloride
  参考文献：
  名称：

  A stereoselective approach to peptidomimetic BACE1 inhibitors

  摘要：

  Aiming at identifying new scaffolds to generate beta-secretase (BACE1) inhibitors we developed peptidomimetics based on a 1,4-benzodiazepine core (3a-d), their seco-analogs (4a-b), and linear analogs (5a-h), by stereoselective approaches. We herein discuss the synthesis, molecular modeling and in vitro studies for the newly developed ligands. Compounds 5c and 5h behaved as BACE1 inhibitors on the isolated enzyme and in cellular studies. Particularly, for its low molecular weight, inhibitor 5h is a prototypic hit to develop a series of BACE1 inhibitors more potent and active on whole-cells. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.09.056
• 作为产物：
  描述：

  六氯丙酮 、 N-(3-((((R)-1-(tert-butyldimethylsilyl)oxy))-2-(((1S)-1-benzyl-(2-(tert-butyldimethylsilyl)oxy)ethyl)(tert-butoxycarbonylamino))ethyl)phenyl)amine 、 Cbz-L-苯甘氨酸 在 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 1.75h， 以25%的产率得到(2S)-2-(benzyloxycarbonylamino)-N-(3-(((R)-1-hydroxy)-2-(((1S)-1-benzyl-2-hydroxyethyl)(tert-butoxycarbonylamino))ethyl)phenyl)-2-phenylacetamide
  参考文献：
  名称：

  A stereoselective approach to peptidomimetic BACE1 inhibitors

  摘要：

  Aiming at identifying new scaffolds to generate beta-secretase (BACE1) inhibitors we developed peptidomimetics based on a 1,4-benzodiazepine core (3a-d), their seco-analogs (4a-b), and linear analogs (5a-h), by stereoselective approaches. We herein discuss the synthesis, molecular modeling and in vitro studies for the newly developed ligands. Compounds 5c and 5h behaved as BACE1 inhibitors on the isolated enzyme and in cellular studies. Particularly, for its low molecular weight, inhibitor 5h is a prototypic hit to develop a series of BACE1 inhibitors more potent and active on whole-cells. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.09.056

文献信息

• A stereoselective approach to peptidomimetic BACE1 inhibitors
  作者：Stefania Butini、Emanuele Gabellieri、Margherita Brindisi、Simone Giovani、Samuele Maramai、Giridhar Kshirsagar、Egeria Guarino、Simone Brogi、Valeria La Pietra、Mariateresa Giustiniano、Luciana Marinelli、Ettore Novellino、Giuseppe Campiani、Andrea Cappelli、Sandra Gemma

  DOI：10.1016/j.ejmech.2013.09.056

  日期：2013.12

  Aiming at identifying new scaffolds to generate beta-secretase (BACE1) inhibitors we developed peptidomimetics based on a 1,4-benzodiazepine core (3a-d), their seco-analogs (4a-b), and linear analogs (5a-h), by stereoselective approaches. We herein discuss the synthesis, molecular modeling and in vitro studies for the newly developed ligands. Compounds 5c and 5h behaved as BACE1 inhibitors on the isolated enzyme and in cellular studies. Particularly, for its low molecular weight, inhibitor 5h is a prototypic hit to develop a series of BACE1 inhibitors more potent and active on whole-cells. (C) 2013 Elsevier Masson SAS. All rights reserved.