tert-butyl N-[(2S)-1-[[(2S)-1-[[(2S)-1-(benzylamino)-3-[(3S)-3-hydroxy-2-oxo-1H-indol-3-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-(4-phenylmethoxyphenyl)propan-2-yl]carbamate | 1257652-86-0

• 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: tert-butyl N-[(2S)-1-[[(2S)-1-[[(2S)-1-(benzylamino)-3-[(3S)-3-hydroxy-2-oxo-1H-indol-3-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-(4-phenylmethoxyphenyl)propan-2-yl]carbamate
• CAS: 1257652-86-0
• 化学式: C₄₂H₄₇N₅O₈
• 分子量: 749.864
• InChiKey: LEFDHTPNDGQXKD-ITADJZSCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  55
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  184
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  Boc-Tyr(Bzl)-D-Ala-OH 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 N,N-二甲基甲酰胺-d7 为溶剂， 生成 tert-butyl N-[(2S)-1-[[(2S)-1-[[(2S)-1-(benzylamino)-3-[(3S)-3-hydroxy-2-oxo-1H-indol-3-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-(4-phenylmethoxyphenyl)propan-2-yl]carbamate
  参考文献：
  名称：

  Structure-based design of human immuno- and constitutive proteasomes inhibitors

  摘要：

  Starting from the X-ray structure of our previous tripeptidic linear mimics of TMC-95A in complex with yeast 20S proteasome, we introduced new structural features to induce a differential inhibition between human constitutive and immunoproteasome 20S particles. Libraries of 24 tripeptidic and 6 dipeptidic derivatives were synthesized. The optimized preparation of 3-hydroxyoxindolyl alanine residues from tryptophan and their incorporation in peptides were described. Several potent inhibitors of human constitutive proteasome and immunoproteasome acting at the nanomolar level (IC50 = 7.1 nM against the chymotrypsin-like activity for the best inhibitor) were obtained. A cytotoxic effect at the submicromolar level was observed against 6 human cancer cell lines. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.01.013

文献信息

• Structure-based design of human immuno- and constitutive proteasomes inhibitors
  作者：Nicolas Richy、Daad Sarraf、Xavier Maréchal、Naëla Janmamode、Rémy Le Guével、Emilie Genin、Michèle Reboud-Ravaux、Joëlle Vidal

  DOI：10.1016/j.ejmech.2018.01.013

  日期：2018.2

  Starting from the X-ray structure of our previous tripeptidic linear mimics of TMC-95A in complex with yeast 20S proteasome, we introduced new structural features to induce a differential inhibition between human constitutive and immunoproteasome 20S particles. Libraries of 24 tripeptidic and 6 dipeptidic derivatives were synthesized. The optimized preparation of 3-hydroxyoxindolyl alanine residues from tryptophan and their incorporation in peptides were described. Several potent inhibitors of human constitutive proteasome and immunoproteasome acting at the nanomolar level (IC50 = 7.1 nM against the chymotrypsin-like activity for the best inhibitor) were obtained. A cytotoxic effect at the submicromolar level was observed against 6 human cancer cell lines. (C) 2018 Elsevier Masson SAS. All rights reserved.