(R)-4-benzyl-3-((S)-2-benzylpent-4-enoyl)oxazolidin-2-one | 255915-27-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (R)-4-benzyl-3-((S)-2-benzylpent-4-enoyl)oxazolidin-2-one
• 英文别名: (4R)-4-benzyl-3-[(2S)-2-benzylpent-4-enoyl]-1,3-oxazolidin-2-one
• CAS: 255915-27-6
• 化学式: C₂₂H₂₃NO₃
• 分子量: 349.43
• InChiKey: QYGUPQFVBANGOJ-VQTJNVASSA-N

物化性质

• 沸点：
  528.9±39.0 °C(Predicted)
• 密度：
  1.168±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-4-benzyl-3-((S)-2-benzylpent-4-enoyl)oxazolidin-2-one 在 palladium on activated charcoal sodium chlorite 、 正丁基锂 、 disodium hydrogenphosphate 、 2-甲基-2-丁烯 、 氢气 、 臭氧 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 叔丁醇 为溶剂， 反应 4.42h， 生成 R-2-苄基琥珀酸
  参考文献：
  名称：

  Stereochemistry in enzyme inhibition: synthesis and evaluation of enantiomerically pure 2-benzyl-3-formylpropanoic acids as inhibitors of carboxypeptidase A

  摘要：

  Both enantiomers of 2-benzyl-3-formylpropanoic acid were synthesized in five steps starting with hydrocinnamic acid and each enantiomer assayed for inhibitory activity against carboxypeptidase A to find that the (R)-form is 674-fold more potent than its enantiomer. The finding that the (R)-form which belongs to the L-series is mostly responsible for the inhibitory activity accords with the explanation that the present inhibitor is a transition state analog inhibitor because, as such, its stereochemistry should belong to the same series as that of the substrate, i.e., the L-series. The gem-diol form of the inhibitor generated in situ mimics the transition state in the catalytic process.

  DOI：

  10.1016/s0957-4166(99)00421-8
• 作为产物：
  描述：

  4-戊烯酰氯 在 正丁基锂 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 6.67h， 生成 (R)-4-benzyl-3-((S)-2-benzylpent-4-enoyl)oxazolidin-2-one
  参考文献：
  名称：

  Structural requirements of histone deacetylase inhibitors: C4-modified saha analogs display dual HDAC6/HDAC8 selectivity

  摘要：

  提供一种具有以下化学式I的化合物，用于抑制组蛋白去乙酰化酶：或其药用可接受的盐或水合物，其中R为烷基，C6-18芳基，C5-18杂环芳基，C8-22烷基芳基，C8-22烷基杂环芳基或卤素。

  公开号：

  US20180057448A1

文献信息

• Structural requirements of histone deacetylase inhibitors: C4-modified saha analogs display dual HDAC6/HDAC8 selectivity
  申请人：WAYNE STATE UNIVERSITY

  公开号：US20180057448A1

  公开（公告）日：2018-03-01

  A compound having formula I for histone deacetylase inhibition is provided: or a pharmaceutically acceptable salt or hydrate thereof wherein R is alkyl, C 6-18 aryl, C 5-18 heteroaryl, C 8-22 alkylaryl, C 8-22 alkylheteroaryl, or halo.

  提供一种具有以下化学式I的化合物，用于抑制组蛋白去乙酰化酶：或其药用可接受的盐或水合物，其中R为烷基，C6-18芳基，C5-18杂环芳基，C8-22烷基芳基，C8-22烷基杂环芳基或卤素。
• Structural requirements of histone deacetylase inhibitors: C4-modified SAHA analogs display dual HDAC6/HDAC8 selectivity
  申请人：WAYNE STATE UNIVERSITY

  公开号：US10259779B2

  公开（公告）日：2019-04-16

  A compound having formula I for histone deacetylase inhibition is provided: or a pharmaceutically acceptable salt or hydrate thereof wherein R is alkyl, C6-18 aryl, C5-18 heteroaryl, C8-22 alkylaryl, C8-22 alkylheteroaryl, or halo.

  提供了一种具有式 I 的化合物，用于抑制组蛋白去乙酰化酶： 或其药学上可接受的盐或水合物，其中 R 是烷基、C6-18 芳基、C5-18 杂芳基、C8-22 烷芳基、C8-22 烷基杂芳基或卤素。
• The structural requirements of histone deacetylase inhibitors: C4-modified SAHA analogs display dual HDAC6/HDAC8 selectivity
  作者：Ahmed T. Negmeldin、Joseph R. Knoff、Mary Kay H. Pflum

  DOI：10.1016/j.ejmech.2017.10.076

  日期：2018.1

  Histone deacetylase (HDAC) enzymes govern the post-translational acetylation state of lysine residues on protein substrates, leading to regulatory changes in cell function. Due to their role in cancers, HDAC proteins have emerged as promising targets for cancer treatment. Four HDAC inhibitors have been approved as anti-cancer therapeutics, including SAHA (Suberoylanilide hydroxamic acid, Vorinostat, Zolinza). SAHA is a nonselective HDAC inhibitor that targets most of the eleven HDAC isoforms. The nonselectivity of SAHA might account for its clinical side effects, but certainly limits its use as a chemical tool to study cancer-related HDAC cell biology. Herein, the nonselective HDAC inhibitor SAHA Was modified at the C4 position of the linker to explore activity and selectivity. Several C4-modified SAHA analogs exhibited dual HDAC6/8 selectivity. Interestingly, (R)-C4-benzyl SAHA displayed 520- to 1300-fold selectivity for HDAC6 and HDAC8 over HDAC1, 2, and 3, with IC50 values of 48 and 27 nM with HDAC6 and 8, respectively. In cellulo testing of the inhibitors was consistent with the observed in vitro selectivity. Docking studies provided a structural rationale for selectivity. The C4-SAHA analogs represent useful chemical tools to understand the role of HDAC6 and HDAC8 in cancer biology and exciting lead compounds for targeting of both HDAC6 and HDAC8 in various cancers. (C) 2017 Elsevier Masson SAS. All rights reserved.
• Stereochemistry in enzyme inhibition: synthesis and evaluation of enantiomerically pure 2-benzyl-3-formylpropanoic acids as inhibitors of carboxypeptidase A
  作者：Dong H. Kim、Suhman Chung

  DOI：10.1016/s0957-4166(99)00421-8

  日期：1999.9

  Both enantiomers of 2-benzyl-3-formylpropanoic acid were synthesized in five steps starting with hydrocinnamic acid and each enantiomer assayed for inhibitory activity against carboxypeptidase A to find that the (R)-form is 674-fold more potent than its enantiomer. The finding that the (R)-form which belongs to the L-series is mostly responsible for the inhibitory activity accords with the explanation that the present inhibitor is a transition state analog inhibitor because, as such, its stereochemistry should belong to the same series as that of the substrate, i.e., the L-series. The gem-diol form of the inhibitor generated in situ mimics the transition state in the catalytic process.