tert-butyl (R)-3-((S)-4-benzyl-2-oxooxazolidine-3-carbonyl)heptanoate | 200866-59-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: tert-butyl (R)-3-((S)-4-benzyl-2-oxooxazolidine-3-carbonyl)heptanoate
• 英文别名: tert-butyl (3R)-3-[(4S)-4-benzyl-2-oxo-1,3-oxazolidine-3-carbonyl]heptanoate
• CAS: 200866-59-7
• 化学式: C₂₂H₃₁NO₅
• 分子量: 389.492
• InChiKey: SFBTXSZQAURIJE-MSOLQXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (R)-3-((S)-4-benzyl-2-oxooxazolidine-3-carbonyl)heptanoate 在 lithium hydroxide 、 双氧水 、 三乙胺 、 N,N'-羰基二咪唑 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 (3R)-3-[[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]carbamoyl]heptanoic acid
  参考文献：
  名称：

  Matrix Metalloproteinase Inhibitors:  A Structure−Activity Study

  摘要：

  Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids in addition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (1) Two key hydrogen bonds must be present between the enzyme and potent substrates. (2) Potent inhibitors must possess strong zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustrated by its ability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.

  DOI：

  10.1021/jm970494j
• 作为产物：
  描述：

  (S)-4-苄基-2-唑烷酮 在 4-二甲氨基吡啶 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 tert-butyl (R)-3-((S)-4-benzyl-2-oxooxazolidine-3-carbonyl)heptanoate
  参考文献：
  名称：

  新型肌动蛋白衍生物作为HsPDF抑制剂的合成及其抗癌活性。

  摘要：

  人线粒体肽去甲酰基化酶（HsPDF）负责从新合成的线粒体蛋白的N末端甲酰基甲硫氨酸中去除甲酰基，并在维持线粒体功能中发挥重要作用。它在各种癌症中过表达，并已被提议作为一种新型治疗靶标。肌动蛋白是一种天然的拟肽HsPDF抑制剂，据报道在体外能抑制多种人类癌细胞的增殖。但是，其功效和药代动力学特性需要显着改善以达到治疗目的。为了获得作为抗癌治疗剂的HsPDF抑制剂，我们筛选了肌动蛋白衍生物的内部集合，并发现了两个具有抗增殖活性的初始产物。沿拟肽骨架的进一步优化导致包含取代的苯基部分的两个系列的化合物。它们是有效的HsPDF抑制剂，在选定的癌细胞系中表现出极大的抗增殖活性。最后，复合15m在异种移植动物模型中显着抑制了人类结肠癌的生长。

  DOI：

  10.1021/acs.jmedchem.0c00079

文献信息

• Peptide deformylase inhibitors of Mycobacterium tuberculosis: Synthesis, structural investigations, and biological results
  作者：Arkadius Pichota、Jeyaraj Duraiswamy、Zheng Yin、Thomas H. Keller、Jenefer Alam、Sarah Liung、Gladys Lee、Mei Ding、Gang Wang、Wai Ling Chan、Mark Schreiber、Ida Ma、David Beer、Xinyi Ngew、Kakoli Mukherjee、Mahesh Nanjundappa、Jeanette W.P. Teo、Pamela Thayalan、Amelia Yap、Thomas Dick、Wuyi Meng、Mei Xu、James Koehn、Shi-Hao Pan、Kirk Clark、Xiaoling Xie、Carolyn Shoen、Michael Cynamon

  DOI：10.1016/j.bmcl.2008.10.040

  日期：2008.12

  Bacterial peptide deformylase (PDF) belongs to a subfamily of metalloproteases catalyzing the removal of the N-terminal formyl group from newly synthesized proteins. We report the synthesis and biological activity of highly potent inhibitors of Mycobacterium tuberculosis (Mtb) PDF enzyme as well as the first X-ray crystal structure of Mtb PDF. Structure-activity relationship and crystallographic data clarified the structural requirements for high enzyme potency and cell based potency. Activities against single and multi-drug-resistant Mtb strains are also reported.
• Matrix Metalloproteinase Inhibitors:  A Structure−Activity Study
  作者：Daniel E. Levy、France Lapierre、Weisheng Liang、Wenqing Ye、Christopher W. Lange、Xiaoyuan Li、Damian Grobelny、Marie Casabonne、David Tyrrell、Kevin Holme、Alex Nadzan、Richard E. Galardy

  DOI：10.1021/jm970494j

  日期：1998.1.1

  Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids in addition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (1) Two key hydrogen bonds must be present between the enzyme and potent substrates. (2) Potent inhibitors must possess strong zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustrated by its ability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.
• Synthesis and Anticancer Activity of Novel Actinonin Derivatives as HsPDF Inhibitors
  作者：Liu Hu、Xing Cai、Suzhen Dong、Yongjia Zhen、Jidi Hu、Shenjun Wang、Jingwen Jiang、Jiawu Huang、Yuqiao Han、Yu Qian、Yanqiu Yuan、Wenhao Hu

  DOI：10.1021/acs.jmedchem.0c00079

  日期：2020.7.9

  various cancers and has been proposed as a novel therapeutic target. Actinonin, a naturally occurring peptidomimetic HsPDF inhibitor, was reported to inhibit the proliferation of a broad spectrum of human cancer cells in vitro. However, its efficacy and pharmacokinetic profile requires significant improvement for therapeutic purposes. To obtain HsPDF inhibitors as anticancer therapeutics, we screened

  人线粒体肽去甲酰基化酶（HsPDF）负责从新合成的线粒体蛋白的N末端甲酰基甲硫氨酸中去除甲酰基，并在维持线粒体功能中发挥重要作用。它在各种癌症中过表达，并已被提议作为一种新型治疗靶标。肌动蛋白是一种天然的拟肽HsPDF抑制剂，据报道在体外能抑制多种人类癌细胞的增殖。但是，其功效和药代动力学特性需要显着改善以达到治疗目的。为了获得作为抗癌治疗剂的HsPDF抑制剂，我们筛选了肌动蛋白衍生物的内部集合，并发现了两个具有抗增殖活性的初始产物。沿拟肽骨架的进一步优化导致包含取代的苯基部分的两个系列的化合物。它们是有效的HsPDF抑制剂，在选定的癌细胞系中表现出极大的抗增殖活性。最后，复合15m在异种移植动物模型中显着抑制了人类结肠癌的生长。