3β-[(2'-hydroxybenzoyl)oxy]-1R-(exo,exo)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid isopropyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3β-[(2'-hydroxybenzoyl)oxy]-1R-(exo,exo)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid isopropyl ester
• 英文别名: propan-2-yl (1R,2R,3S,5S)-3-(2-hydroxybenzoyl)oxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• 化学式: C₁₉H₂₅NO₅
• 分子量: 347.411
• InChiKey: LIJBSQOBIXLKCG-JSQNDZKTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  古卡因 在 盐酸 、 三乙胺 作用下， 以 异丙醇 、 苯 为溶剂， 反应 48.0h， 生成 3β-[(2'-hydroxybenzoyl)oxy]-1R-(exo,exo)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid isopropyl ester
  参考文献：
  名称：

  Synthesis and dopamine transporter binding of 2β-isopropyl ester analogs of cocaine

  摘要：

  A series of 2beta-isopropyl ester analogs of cocaine (7-11) was synthesised and evaluated in an in vitro dopamine transporter (DAT) binding assays. Ecgonine HCl (5) was obtained from (-)-cocaine (1) by hydrolysis using I N HCl. Acid catalysed esterification of 5 using 2-propanol and HCl gas afforded 2beta-isopropyl ecgonine (6). Compounds 7-9 were obtained via esterification of the 3beta-hydroxyl group of 6 using the appropriate acid chloride. Compound 10 was obtained via selective hydrolysis and re-esterification of 7 using 2-propanol and HCl gas. Compound I I was obtained by reduction of 9 using H-2/Pd-C. Compounds 7, 10 and I I showed high binding affinity to the DAT (as indicated from the inhibition of the binding of [H-3]WIN 35,428 (3)) with IC50 values (mean +/- S.E.M.) 208.5 +/- 9.5, 47.43 +/- 1.79 and 11.25 +/- 3.37 nM, respectively). Compound 7 is comparatively as active as cocaine, 10 is ca. fivefold more active than cocaine and 11 is ca. 20-fold more active than cocaine and even twice more active than the radioligand 3. Compound It, like its methyl ester analog (2' aminococaine), exhibited the highest affinity to the DAT. These results, along with previous results, emphasise the importance of a hydrogen-bond donor group at the T-position of cocaine and its isopropyl ester analogs to enhance binding affinity to the DAT. (C) 2002 Published by Editions scientifiques et medicalcs Elsevier SAS.

  DOI：

  10.1016/s0223-5234(01)01314-9

文献信息

• Synthesis and dopamine transporter binding of 2β-isopropyl ester analogs of cocaine
  作者：T El-Moselhy

  DOI：10.1016/s0223-5234(01)01314-9

  日期：2002.2

  A series of 2beta-isopropyl ester analogs of cocaine (7-11) was synthesised and evaluated in an in vitro dopamine transporter (DAT) binding assays. Ecgonine HCl (5) was obtained from (-)-cocaine (1) by hydrolysis using I N HCl. Acid catalysed esterification of 5 using 2-propanol and HCl gas afforded 2beta-isopropyl ecgonine (6). Compounds 7-9 were obtained via esterification of the 3beta-hydroxyl group of 6 using the appropriate acid chloride. Compound 10 was obtained via selective hydrolysis and re-esterification of 7 using 2-propanol and HCl gas. Compound I I was obtained by reduction of 9 using H-2/Pd-C. Compounds 7, 10 and I I showed high binding affinity to the DAT (as indicated from the inhibition of the binding of [H-3]WIN 35,428 (3)) with IC50 values (mean +/- S.E.M.) 208.5 +/- 9.5, 47.43 +/- 1.79 and 11.25 +/- 3.37 nM, respectively). Compound 7 is comparatively as active as cocaine, 10 is ca. fivefold more active than cocaine and 11 is ca. 20-fold more active than cocaine and even twice more active than the radioligand 3. Compound It, like its methyl ester analog (2' aminococaine), exhibited the highest affinity to the DAT. These results, along with previous results, emphasise the importance of a hydrogen-bond donor group at the T-position of cocaine and its isopropyl ester analogs to enhance binding affinity to the DAT. (C) 2002 Published by Editions scientifiques et medicalcs Elsevier SAS.