(R)-1-[((2S,3S)-3-hexyl-4-oxooxetan-2-yl)hept-5-en-2-yl] 2-methanamido ethanoate | 1057856-54-8

• 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: (R)-1-[((2S,3S)-3-hexyl-4-oxooxetan-2-yl)hept-5-en-2-yl] 2-methanamido ethanoate
• 英文别名: (R)-1-((2S,3S)-3-hexyl-4-oxooxetan-2-yl)hept-5-en-2-yl 2-methanamidoethanoate；[(2R)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]hept-5-en-2-yl] 2-formamidoacetate
• CAS: 1057856-54-8
• 化学式: C₁₉H₃₁NO₅
• 分子量: 353.459
• InChiKey: YEWKKVDDJYHYSQ-IKGGRYGDSA-N

物化性质

• 沸点：
  500.4±30.0 °C(Predicted)
• 密度：
  1.053±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (3S,4S)-3-hexyl-4-((2R,5E)-2-hydroxyhept-5-enyl)oxetan-2-one 、 N-甲酰甘氨酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 二氯甲烷 为溶剂， 反应 13.0h， 以57%的产率得到(R)-1-[((2S,3S)-3-hexyl-4-oxooxetan-2-yl)hept-5-en-2-yl] 2-methanamido ethanoate
  参考文献：
  名称：

  Synthesis of Novel β-Lactone Inhibitors of Fatty Acid Synthase

  摘要：

  Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report oil the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a beta-lactone as the central pharmacophore, 28 novel congeners were synthesized and examined. Structural features such as the length of the alpha- and beta-alkyl chains, their chemical composition, and arnino ester substitutions were altered and tile resulting compounds explored for inhibitory activity toward the thioesterase domain of FAS. Nineteen congeners show improved potency for FAS in biochemical assays relative to orlistat. Three of that subset, including the natural product valilactone, also display all increased potency in inducing tumor cell death and improved solubility compared to orlistat. These findings Support the idea that all orlistat congener can be optimized for use in a preclinical drug design and for clinical drug development.

  DOI：

  10.1021/jm800321h

文献信息

• BETA-LACTONE COMPOUNDS
  申请人：Smith Jeffrey W.

  公开号：US20090124681A1

  公开（公告）日：2009-05-14

  The present invention provides compounds having the general structure A, or a pharmaceutically acceptable derivatives thereof: wherein R is an alkyl group, and R 1 comprises at least one moiety selected from a group consisting of an alkyl, an alkenyl, an aryl, a heterocycle, hydroxyl, ester, amido, aldehyde, and a halogen.

  本发明提供具有一般结构A或其药学上可接受的衍生物的化合物：其中R是烷基，而R1包括至少一种从以下组中选择的基团：烷基，烯基，芳基，杂环，羟基，酯基，酰胺基，醛基和卤素。
• Beta-lactone compounds
  申请人：Burnham Institute for Medical Research

  公开号：US08258321B2

  公开（公告）日：2012-09-04

  The present invention provides compounds having the general structure A, or a pharmaceutically acceptable derivatives thereof: wherein R is an alkyl group, and R1 comprises at least one moiety selected from a group consisting of an alkyl, an alkenyl, an aryl, a heterocycle, hydroxyl, ester, amido, aldehyde, and a halogen.

  本发明提供具有一般结构A或其药学上可接受的衍生物的化合物：其中R为烷基，R1包括至少一种从烷基，烯基，芳基，杂环，羟基，酯，酰胺，醛和卤素组成的基团。
• Synthesis of Novel β-Lactone Inhibitors of Fatty Acid Synthase
  作者：Robyn D. Richardson、Gil Ma、Yatsandra Oyola、Manuel Zancanella、Lynn M. Knowles、Piotr Cieplak、Daniel Romo、Jeffrey W. Smith

  DOI：10.1021/jm800321h

  日期：2008.9.11

  Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report oil the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a beta-lactone as the central pharmacophore, 28 novel congeners were synthesized and examined. Structural features such as the length of the alpha- and beta-alkyl chains, their chemical composition, and arnino ester substitutions were altered and tile resulting compounds explored for inhibitory activity toward the thioesterase domain of FAS. Nineteen congeners show improved potency for FAS in biochemical assays relative to orlistat. Three of that subset, including the natural product valilactone, also display all increased potency in inducing tumor cell death and improved solubility compared to orlistat. These findings Support the idea that all orlistat congener can be optimized for use in a preclinical drug design and for clinical drug development.