(1-(3-(tert-butyldimethylsilyloxy)-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(6-fluoropyridin-3-yl)methanone

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (1-(3-(tert-butyldimethylsilyloxy)-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(6-fluoropyridin-3-yl)methanone
• 英文别名: [1-[(2S,3S)-3-[tert-butyl(dimethyl)silyl]oxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-yl]-(6-fluoropyridin-3-yl)methanone
• 化学式: C₂₇H₃₇FN₂O₂Si
• 分子量: 468.687
• InChiKey: CRSBNFADUYXOHW-ZEQRLZLVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.67
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1-(3-(tert-butyldimethylsilyloxy)-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(6-fluoropyridin-3-yl)methanone 在 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以79%的产率得到(6-fluoropyridin-3-yl)(1-(3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)methanone
  参考文献：
  名称：

  Heteroaromatic and Aniline Derivatives of Piperidines As Potent Ligands for Vesicular Acetylcholine Transporter

  摘要：

  To identify suitable lipophilic compounds having high potency and selectivity for vesicular acetylcholine transporter (VAChT), a heteroaromatic ring or a phenyl group was introduced into the carbonyl-containing scaffold for VAChT ligands. Twenty new compounds with ALogD values between 0.53 and 3.2 were synthesized, and their in vitro binding affinities were assayed. Six of them (19a, 19e, 19g, 19k, and 24a-b) displayed high affinity for VAChT (K-i = 0.93-18 nM for racemates) and moderate to high selectivity for VAChT over sigma(1) and sigma(2) receptors (K-i = 44-4400-fold). These compounds have a methyl or a fluoro substitution that provides the position for incorporating PET radioisotopes C-11 or F-18. Compound (-)-[C-11]24b (K-i = 0.78 nM for VAChT, 1200-fold over sigma receptors) was successfully synthesized and evaluated in vivo in rats and nonhuman primates. The data revealed that (-)-[C-11]24b has highest binding in striatum and has favorable pharmacokinetics in the brain.

  DOI：

  10.1021/jm400664x
• 作为产物：
  描述：

  1-Boc-4-[甲氧基(甲基)氨基甲酰]哌嗪 在 咪唑 、 正丁基锂 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 44.75h， 生成 (1-(3-(tert-butyldimethylsilyloxy)-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(6-fluoropyridin-3-yl)methanone
  参考文献：
  名称：

  Heteroaromatic and Aniline Derivatives of Piperidines As Potent Ligands for Vesicular Acetylcholine Transporter

  摘要：

  To identify suitable lipophilic compounds having high potency and selectivity for vesicular acetylcholine transporter (VAChT), a heteroaromatic ring or a phenyl group was introduced into the carbonyl-containing scaffold for VAChT ligands. Twenty new compounds with ALogD values between 0.53 and 3.2 were synthesized, and their in vitro binding affinities were assayed. Six of them (19a, 19e, 19g, 19k, and 24a-b) displayed high affinity for VAChT (K-i = 0.93-18 nM for racemates) and moderate to high selectivity for VAChT over sigma(1) and sigma(2) receptors (K-i = 44-4400-fold). These compounds have a methyl or a fluoro substitution that provides the position for incorporating PET radioisotopes C-11 or F-18. Compound (-)-[C-11]24b (K-i = 0.78 nM for VAChT, 1200-fold over sigma receptors) was successfully synthesized and evaluated in vivo in rats and nonhuman primates. The data revealed that (-)-[C-11]24b has highest binding in striatum and has favorable pharmacokinetics in the brain.

  DOI：

  10.1021/jm400664x