S-methyl 5-(2-(7-phenylheptanoyl)oxazol-5-yl)pentanethioate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: S-methyl 5-(2-(7-phenylheptanoyl)oxazol-5-yl)pentanethioate
• 化学式: C₂₂H₂₉NO₃S
• 分子量: 387.543
• InChiKey: XRLYGLZYTDVTOA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.65
• 重原子数：
  27.0
• 可旋转键数：
  13.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  60.17
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  戊-4-炔酸甲酯 在 copper(l) iodide 、 N-羟基-7-氮杂苯并三氮唑 、 trans-bis(triphenylphosphine)palladium dichloride 、 palladium 10% on activated carbon 、 四丁基氟化铵 、 氢气 、 戴斯-马丁氧化剂 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 S-methyl 5-(2-(7-phenylheptanoyl)oxazol-5-yl)pentanethioate
  参考文献：
  名称：

  Design, Synthesis, and Characterization of α-Ketoheterocycles That Additionally Target the Cytosolic Port Cys269 of Fatty Acid Amide Hydrolase

  摘要：

  A series of alpha-ketooxazoles incorporating electrophiles at the C5 position of the pyridyl ring of 2 (OL-135) and related compounds were prepared and examined as inhibitors of fatty acid amide hydrolase (FAAH) that additionally target the cytosolic port Cys269. From this series, a subset of the candidate inhibitors exhibited time-dependent FAAH inhibition and noncompetitive irreversible inactivation of the enzyme, consistent with the targeted Cys269 covalent alkylation or addition, and maintained or enhanced the intrinsic selectivity for FAAH versus other serine hydrolases. A preliminary in vivo assessment demonstrates that these inhibitors raise endogenous brain levels of anandamide and other FAAH substrates upon intraperitoneal (i.p.) administration to mice, with peak levels achieved within 1.5-3 h, and that the elevations of the signaling lipids were maintained >6 h, indicating that the inhibitors effectively reach and remain active in the brain, inhibiting FAAH for a sustained period.

  DOI：

  10.1021/jm401820q