N-(2,2,2-trichloroethylcarbamoyl)-2β-carbomethoxy-3β-(4'-fluorophenyl)nortropane | 303733-95-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: N-(2,2,2-trichloroethylcarbamoyl)-2β-carbomethoxy-3β-(4'-fluorophenyl)nortropane
• CAS: 303733-95-1
• 化学式: C₁₈H₁₉Cl₃FNO₄
• 分子量: 438.711
• InChiKey: QIMOUGBFGPXSKV-YJNKXOJESA-N

物化性质

• 沸点：
  480.3±45.0 °C(Predicted)
• 密度：
  1.422±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.44
• 重原子数：
  27.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.84
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-(2,2,2-trichloroethylcarbamoyl)-2β-carbomethoxy-3β-(4'-fluorophenyl)nortropane 在 溶剂黄146 、 potassium iodide 、 锌 作用下， 以 乙醇 为溶剂， 反应 32.0h， 生成 甲基(1R,2S,3S,5S)-3-(4-氟苯基)-8-丙-2-烯基-8-氮杂双环[3.2.1]辛烷-2-羧酸酯
  参考文献：
  名称：

  Synthesis and receptor binding of N-substituted tropane derivatives. High-affinity ligands for the cocaine receptor

  摘要：

  The synthesis and pharmacological characterization of a series of N-substituted 3-(4-fluorophenyl)tropane derivatives is reported. The compounds displayed binding characteristics that paralleled those of cocaine, and several had substantially higher affinity at cocaine recognition sites. Conjugate addition of 4-fluorophenyl magnesium bromide to anhydroecgonine methyl ester gave 2-beta-(carbomethoxy)-3-beta-(4-fluorophenyl)tropane (4a, designated CFT, also known as WIN 35,428) after flash chromatography. N demethylation of 4a was effected by Zn/HOAc reduction of the corresponding 2,2,2-trichloroethyl carbamate to give 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)nortropane (5), which was alkylated with allyl bromide to afford the N-allyl analogue, 6. The N-propyl analogue, 7, was prepared by catalytic reduction (Pd/C) of 6. The most potent analogue, 4a, was tritiated at a specific activity of 81.3 Ci/mmol. [H-3]4a bound rapidly and reversibly to caudate putamen membranes; the two-component binding curve typical of cocaine analogues was observed. Equilibrium was achieved within 2 h and was stable for at least 4 h. High- and low-affinity K(d) values observed for [H-3]4a (4.7 and 60 nM, respectively) were more than 4 times lower than those for [H-3]cocaine, and the density of binding sites (B(max) = 50 pmol/g, high, and 290 pmol/g, low) for the two drugs were comparable. Nonspecific binding of [H-3]4a was 5-10% of total binding.

  DOI：

  10.1021/jm00109a029
• 作为产物：
  描述：

  4-氟苯基溴化镁 以 乙醚 、 甲苯 为溶剂， 反应 2.0h， 生成 N-(2,2,2-trichloroethylcarbamoyl)-2β-carbomethoxy-3β-(4'-fluorophenyl)nortropane
  参考文献：
  名称：

  Synthesis and receptor binding of N-substituted tropane derivatives. High-affinity ligands for the cocaine receptor

  摘要：

  The synthesis and pharmacological characterization of a series of N-substituted 3-(4-fluorophenyl)tropane derivatives is reported. The compounds displayed binding characteristics that paralleled those of cocaine, and several had substantially higher affinity at cocaine recognition sites. Conjugate addition of 4-fluorophenyl magnesium bromide to anhydroecgonine methyl ester gave 2-beta-(carbomethoxy)-3-beta-(4-fluorophenyl)tropane (4a, designated CFT, also known as WIN 35,428) after flash chromatography. N demethylation of 4a was effected by Zn/HOAc reduction of the corresponding 2,2,2-trichloroethyl carbamate to give 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)nortropane (5), which was alkylated with allyl bromide to afford the N-allyl analogue, 6. The N-propyl analogue, 7, was prepared by catalytic reduction (Pd/C) of 6. The most potent analogue, 4a, was tritiated at a specific activity of 81.3 Ci/mmol. [H-3]4a bound rapidly and reversibly to caudate putamen membranes; the two-component binding curve typical of cocaine analogues was observed. Equilibrium was achieved within 2 h and was stable for at least 4 h. High- and low-affinity K(d) values observed for [H-3]4a (4.7 and 60 nM, respectively) were more than 4 times lower than those for [H-3]cocaine, and the density of binding sites (B(max) = 50 pmol/g, high, and 290 pmol/g, low) for the two drugs were comparable. Nonspecific binding of [H-3]4a was 5-10% of total binding.

  DOI：

  10.1021/jm00109a029

文献信息

• Fluoralkenyl nortropanes
  申请人：Emory University

  公开号：US06344179B1

  公开（公告）日：2002-02-05

  Provided are compounds of the following formula: wherein R is C2-C6 mono- or multi-unsaturated hydrocarbon having one or more ethylene, acetylene or allene groups, A is 18 or 19, and X is H or halogen. The compounds of the invention bind to dopamine transporter with high affinity and selectivity and are thus useful as diagnostic and therapeutic agents for diseases associated with dopamine transporter dysfunction. The radiolabeled compounds are useful as imaging agents for visualizing the location and density of dopamine transporter by PET imaging.

  提供的化合物具有以下公式：其中R是具有一个或多个乙烯、乙炔或戊二烯基团的C2-C6单烯烃或多烯烃碳氢化合物，A为18或19，X为H或卤素。该发明的化合物具有高亲和力和选择性地结合多巴胺转运蛋白，因此可用作与多巴胺转运蛋白功能障碍相关的疾病的诊断和治疗药物。放射标记的化合物可用作PET成像来可视化多巴胺转运蛋白的位置和密度。