methyl 6-(2-(6-phenyl-1,2,3,4-tetrahydronaphthalene-2-carbonyl)oxazol-5-yl)picolinate | 1289561-39-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl 6-(2-(6-phenyl-1,2,3,4-tetrahydronaphthalene-2-carbonyl)oxazol-5-yl)picolinate
• 英文别名: methyl (S)-6-(2-(6-phenyl-1,2,3,4-tetrahydronaphthalen-2-carbonyl)oxazol-5-yl)picolinate；(S)-methyl 6-(2-(6-phenyl-1,2,3,4-tetrahydronaphthalene-2-carbonyl)oxazol-5-yl)picolinate；methyl 6-[2-[(2S)-6-phenyl-1,2,3,4-tetrahydronaphthalene-2-carbonyl]-1,3-oxazol-5-yl]pyridine-2-carboxylate
• CAS: 1289561-39-2
• 化学式: C₂₇H₂₂N₂O₄
• 分子量: 438.483
• InChiKey: XCJYQTBTCKPUDK-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  82.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 6-(2-(6-phenyl-1,2,3,4-tetrahydronaphthalene-2-carbonyl)oxazol-5-yl)picolinate 在 三甲基氢氧化锡 、 potassium hydrogensulfate 作用下， 以 1,2-二氯乙烷 、 水 、 乙酸乙酯 为溶剂， 反应 16.0h， 生成 6-(2-(6-phenyl-1,2,3,4-tetrahydronaphthalene-2-carbonyl)oxazol-5-yl)picolinic acid
  参考文献：
  名称：

  [EN] ALPHA-KETOHETEROCYCLES AND METHODS OF MAKING AND USING
  [FR] ALPHA-CÉTOHÉTÉROCYCLES ET LEURS PROCÉDÉS DE FABRICATION ET D'UTILISATION

  摘要：

  抑制脂肪酸酰胺水解酶的有效化合物已被披露，该酶负责代谢内源大麻素如阿南胺。这些化合物可用作镇痛化合物和诱导睡眠的化合物，可经口服给药，并具有相对较长的作用持续时间。还提供了这些化合物的制备方法。这些化合物是杂环酮的构象约束类似物，如噁唑基酮。

  公开号：

  WO2012106569A1
• 作为产物：
  描述：

  1,2,3,4-四氢-6-羟基-2-萘羧酸 在 吡啶 、 咪唑 、 lithium aluminium tetrahydride 、 四(三苯基膦)钯 、 正丁基锂 、 硼烷四氢呋喃络合物 、 硫酸 、 四丁基氟化铵 、 sodium carbonate 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.75h， 生成 methyl 6-(2-(6-phenyl-1,2,3,4-tetrahydronaphthalene-2-carbonyl)oxazol-5-yl)picolinate
  参考文献：
  名称：

  Reversible Competitive α-Ketoheterocycle Inhibitors of Fatty Acid Amide Hydrolase Containing Additional Conformational Constraints in the Acyl Side Chain: Orally Active, Long-Acting Analgesics

  摘要：

  A series of alpha-ketooxazoles containing conformational constraints in the C2 acyl side chain of 2 (OL-135) were examined as inhibitors of fatty acid amide hydrolase (FAAH). Only one of the two possible enantiomers displayed potent FAAH inhibition (S vs R enantiomer), and their potency is comparable or improved relative to 2, indicating that the conformational restriction in the C2 acyl side chain is achievable. A cocrystal X-ray structure of the alpha-ketoheterocycle 12 bound to a humanized variant of rat FAAH revealed its binding details, confirmed that the (S)-enantiomer is the bound active inhibitor, shed light on the origin of the enantiomeric selectivity, and confirmed that the catalytic Ser241 is covalently bound to the electrophilic carbonyl as a deprotonated hemiketal. Preliminary in vivo characterization of the inhibitors 12 and 14 is reported demonstrating that they raise brain anandamide levels following either intraperitoneal (ip) or oral (po) administration indicative of effective in vivo FAAH inhibition. Significantly, the oral administration of 12 caused dramatic accumulation of anandamide in the brain, with peak levels achieved between 1.5 and 3 h, and these elevations were maintained over 9 h. Additional studies of these two representative members of the series (12 and 14) in models of thermal hyperalgesia and neuropathic pain are reported, including the demonstration that 12 administered orally significantly attenuated mechanical (> 6 h) and cold (> 9 h) allodynia for sustained periods consistent with its long-acting effects in raising the endogenous concentration of anandamide.

  DOI：

  10.1021/jm101597x