3-Naphthalen-2-yl-bicyclo[3.2.1]oct-2-ene-2-carboxylic acid methyl ester | 269064-10-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 3-Naphthalen-2-yl-bicyclo[3.2.1]oct-2-ene-2-carboxylic acid methyl ester
• 英文别名: methyl 3-naphthalen-2-ylbicyclo[3.2.1]oct-2-ene-2-carboxylate
• CAS: 269064-10-0
• 化学式: C₂₀H₂₀O₂
• 分子量: 292.378
• InChiKey: IAFRIOJGEFDYRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-Naphthalen-2-yl-bicyclo[3.2.1]oct-2-ene-2-carboxylic acid methyl ester 在 10percent Pd/C 氢气 作用下， 以 甲醇 为溶剂， 以70 mg的产率得到2α-carbomethoxy-3α-(2-naphthyl)bicyclo[3.2.1]octane
  参考文献：
  名称：

  2-Carbomethoxy-3-aryl-8-bicyclo[3.2.1]octanes:  Potent Non-Nitrogen Inhibitors of Monoamine Transporters

  摘要：

  Cocaine is a potent central nervous system stimulant with severe addiction liability. Its reinforcing and stimulant properties derive from inhibition of monoamine transport systems, in particular the dopamine transporter (DAT). This inhibition results in an increase in synaptic dopamine with subsequent stimulation of postsynaptic dopamine receptors. A wide variety of ligands manifest potent inhibition of the DAT, and these ligands include 3-aryltropane as well as 8-oxa-3-aryltropane analogues of cocaine. There has been considerable effort to determine structure-activity relationships of cocaine and congeners, and it is becoming clear that these inhibitors do not all interact with the DAT in the same manner. The functional role of the 8-heteroatom is the focus of this study. We describe the preparation and biology of a series of 2-carbomethoxy-3-arylbicyclo[3.2.1]octane analogues. Results show that methylene substitution of the amine or ether function of the 8-hetero-2-carbomethoxy-3-arylbicyclo[3.2.1]octanes yields potent inhibitors of monoamine transport. Therefore neither nitrogen nor oxygen are prerequisites for binding of tropane-like ligands to monoamine transporters.

  DOI：

  10.1021/jm000191g
• 作为产物：
  描述：

  双环[3,2,1]辛烷-3-酮 在 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium hexamethyldisilazane 、 sodium carbonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 7.5h， 生成 3-Naphthalen-2-yl-bicyclo[3.2.1]oct-2-ene-2-carboxylic acid methyl ester
  参考文献：
  名称：

  2-Carbomethoxy-3-aryl-8-bicyclo[3.2.1]octanes:  Potent Non-Nitrogen Inhibitors of Monoamine Transporters

  摘要：

  Cocaine is a potent central nervous system stimulant with severe addiction liability. Its reinforcing and stimulant properties derive from inhibition of monoamine transport systems, in particular the dopamine transporter (DAT). This inhibition results in an increase in synaptic dopamine with subsequent stimulation of postsynaptic dopamine receptors. A wide variety of ligands manifest potent inhibition of the DAT, and these ligands include 3-aryltropane as well as 8-oxa-3-aryltropane analogues of cocaine. There has been considerable effort to determine structure-activity relationships of cocaine and congeners, and it is becoming clear that these inhibitors do not all interact with the DAT in the same manner. The functional role of the 8-heteroatom is the focus of this study. We describe the preparation and biology of a series of 2-carbomethoxy-3-arylbicyclo[3.2.1]octane analogues. Results show that methylene substitution of the amine or ether function of the 8-hetero-2-carbomethoxy-3-arylbicyclo[3.2.1]octanes yields potent inhibitors of monoamine transport. Therefore neither nitrogen nor oxygen are prerequisites for binding of tropane-like ligands to monoamine transporters.

  DOI：

  10.1021/jm000191g

文献信息

• 3-Aryl-2-carbomethoxybicyclo[3.2.1]oct-2-enes inhibit WIN 35,428 binding potently and selectively at the dopamine transporter
  作者：Peter C. Meltzer、Paul Blundell、Hong Huang、Shanghao Liu、Yaw F. Yong、Bertha K. Madras

  DOI：10.1016/s0968-0896(99)00322-3

  日期：2000.3

  design of potential cocaine antagonists or cocaine substitutes which interact at the dopamine transporter of mammalian systems. This manuscript describes the synthesis and biological evaluation of 8-substituted 2-carbomethoxy-3-arylbicyclo[3.2.1]oct-2-enes. These compounds prove potent and selective inhibitors of the dopamine transporter. Their selectivity results primarily from a reduced inhibitory potency

  寻找可卡因滥用的药物的重点在于设计在哺乳动物系统多巴胺转运蛋白上相互作用的潜在可卡因拮抗剂或可卡因替代品。该手稿描述了8-取代的2-碳甲氧基-3-芳基双环[3.2.1]辛-2-烯的合成及生物学评估。这些化合物证明是多巴胺转运蛋白的有效和选择性抑制剂。它们的选择性主要是由于降低了对5-羟色胺转运蛋白的抑制能力。这项工作支持这样的观点，即在双环[3.2.1]辛烷体系中3-芳基环的取向对这些分子与5-羟色胺转运蛋白的相互作用的影响远比对与多巴胺转运蛋白的相互作用的影响更显着。
• 2-Carbomethoxy-3-aryl-8-bicyclo[3.2.1]octanes:  Potent Non-Nitrogen Inhibitors of Monoamine Transporters
  作者：Peter C. Meltzer、Paul Blundell、Yaw F. Yong、Zhengming Chen、Clifford George、Mario D. Gonzalez、Bertha K. Madras

  DOI：10.1021/jm000191g

  日期：2000.8.1

  Cocaine is a potent central nervous system stimulant with severe addiction liability. Its reinforcing and stimulant properties derive from inhibition of monoamine transport systems, in particular the dopamine transporter (DAT). This inhibition results in an increase in synaptic dopamine with subsequent stimulation of postsynaptic dopamine receptors. A wide variety of ligands manifest potent inhibition of the DAT, and these ligands include 3-aryltropane as well as 8-oxa-3-aryltropane analogues of cocaine. There has been considerable effort to determine structure-activity relationships of cocaine and congeners, and it is becoming clear that these inhibitors do not all interact with the DAT in the same manner. The functional role of the 8-heteroatom is the focus of this study. We describe the preparation and biology of a series of 2-carbomethoxy-3-arylbicyclo[3.2.1]octane analogues. Results show that methylene substitution of the amine or ether function of the 8-hetero-2-carbomethoxy-3-arylbicyclo[3.2.1]octanes yields potent inhibitors of monoamine transport. Therefore neither nitrogen nor oxygen are prerequisites for binding of tropane-like ligands to monoamine transporters.