(2R,3S,4S)-3-butyl-4-(2-hydroxytridecyl)oxetan-2-one | 1151391-99-9

• 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: (2R,3S,4S)-3-butyl-4-(2-hydroxytridecyl)oxetan-2-one
• 英文别名: (3S,4S)-3-butyl-4-[(2R)-2-hydroxytridecyl]oxetan-2-one
• CAS: 1151391-99-9
• 化学式: C₂₀H₃₈O₃
• 分子量: 326.52
• InChiKey: IVEJGUNVILJRTL-QYZOEREBSA-N

物化性质

• 沸点：
  441.8±18.0 °C(predicted)
• 密度：
  0.943±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  23
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-甲酰甘氨酸 、 (2R,3S,4S)-3-butyl-4-(2-hydroxytridecyl)oxetan-2-one 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69%的产率得到(R)-1-[((2S,3S)-3-butyl-4-oxooxetan-2-yl)tridecan-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
• 作为产物：
  描述：

  Tert-butyl-dimethyl-(1-pyridin-2-ylsulfanylhex-1-enoxy)silane 、 (R)-3-(tert-butyldimethylsiloxy)tetradecanal 在 zinc(II) chloride 、 氢氟酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 60.0h， 生成 (2R,3S,4S)-3-butyl-4-(2-hydroxytridecyl)oxetan-2-one 、
  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的化合物，或其药学上可接受的衍生物：其中R是烷基基团，R1包括至少一种从烷基、烯基、芳基、杂环、羟基、酯、酰胺、醛基和卤素组成的基团。
• US8258321B2
  申请人：——

  公开号：US8258321B2

  公开（公告）日：2012-09-04
• [EN] METHOD AND COMPOSITIONS FOR TREATING OBESITY AND INSULIN RESISTANCE<br/>[FR] MÉTHODE ET COMPOSITIONS DE TRAITEMENT DE L'OBÉSITÉ ET DE LA RÉSISTANCE À L'INSULINE
  申请人：OKLAHOMA MED RES FOUND

  公开号：WO2019112996A1

  公开（公告）日：2019-06-13

  The present invention provides a method of treating obesity in a patient by upregulation of mitochondrial chaperones comprising the steps of: providing a pharmaceutically effective amount of a cDNA composition encoding one or more cellular proteins to increase the one or more cellular proteins in the cell and reduced adiposity in the patient.
• 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.