2-carbomethoxy-3-(4-fluorophenyl)-8-oxabicyclo(3.2.1)-2-octene | 192460-75-6

• 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: 2-carbomethoxy-3-(4-fluorophenyl)-8-oxabicyclo(3.2.1)-2-octene
• 英文别名: 2-carbomethoxy-3-(4-fluorophenyl)-8-oxabicyclo[3.2.1]-2-octene；3-(4-Fluoro-phenyl)-8-oxa-bicyclo[3.2.1]oct-2-ene-2-carboxylic acid methyl ester；methyl 3-(4-fluorophenyl)-8-oxabicyclo[3.2.1]oct-2-ene-2-carboxylate
• CAS: 192460-75-6
• 化学式: C₁₅H₁₅FO₃
• 分子量: 262.281
• InChiKey: AQYGKZKOQFVRAD-UHFFFAOYSA-N

物化性质

• 沸点：
  363.3±42.0 °C(Predicted)
• 密度：
  1.253±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-carbomethoxy-3-(4-fluorophenyl)-8-oxabicyclo(3.2.1)-2-octene 在 SmI₂ 作用下， 以 四氢呋喃 为溶剂， 以834 mg (62%)的产率得到(1R,1S)-2β-Carbomethoxy-3β-(4-fluorophenyl)-8-oxabicyclo(3.2.1)octane
  参考文献：
  名称：

  Tropane analogs and methods for inhibition of monoamine transport

  摘要：

  描述了结合到单胺转运体的新的曲普烷类似物，特别是具有6-或7-取代基的8-aza、8carbo和8-oxo曲普烷。本发明的化合物可以是外消旋体、纯R-对映体或纯S-对映体。本发明的某些优选化合物对DAT与SERT具有高选择性。还描述了包含所述化合物的制药治疗组合物，该组合物在药学上可接受的载体中配制，并且通过将所述单胺转运体与本发明的化合物的5-羟色胺再摄取抑制量接触的方法来抑制单胺转运体的5-羟色胺再摄取。本发明实施中的优选单胺转运体包括多巴胺转运体、5-羟色胺转运体和去甲肾上腺素转运体。

  公开号：

  US05948933A1
• 作为产物：
  描述：

  (1S,2S,5R)-3-Oxo-8-oxa-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester 在 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium hexamethyldisilazane 、 sodium carbonate 、 lithium chloride 作用下， 以 various solvent(s) 为溶剂， 反应 1.5h， 生成 2-carbomethoxy-3-(4-fluorophenyl)-8-oxabicyclo(3.2.1)-2-octene
  参考文献：
  名称：

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

  摘要：

  Cocaine is a potent stimulant of the mammalian central nervous system. Its reinforcing and stimulant properties have been associated with its propensity to bind to monoamine transporter systems. It has generally been assumed t;hat the amino function on monoamines is a requirement for binding to monoamine transporters. In particular, the 8-amino function on the tropane skeleton of cocaine and cocaine analogs has been assumed to provide an ionic bond to the aspartic acid residue on the dopamine transporter(DAT). We have prepared the first 8-oxa analogs of the 3-aryltropanes (WIN compounds) and have found that the 3 beta-(3,4-dichlorophenyl) (6g) and 3 alpha-(3,4-dichlorophenyl) (7g) analogs are particularly potent (IC50 = 3.27 and 2.34 nM, respectively) inhibitors of the dopamine transporter. We now describe the synthesis and biology of the family of 2-carbomethoxy-3-aryl-8-oxabicyclo[3.2.1]octanes and demonstrate that an amino nitrogen is not required for binding to the DAT.

  DOI：

  10.1021/jm9703045

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。
• Bridge-substituted tropanes for methods of imaging and therapy
  申请人：Organix, Inc.

  公开号：US05770180A1

  公开（公告）日：1998-06-23

  Disclosed are bridge-substituted analogs of tropanes and benztropines as well as methods for: imaging of cocaine receptors; treatment of cocaine abuse; and imaging and treatment of Parkinson's disease.

  揭示了替桥式的托帕酮和苯托品的类似物，以及用于：可卡因受体成像；治疗可卡因滥用；以及帕金森病的成像和治疗的方法。
• Tropane analogs and methods for inhibition of monoamine
  申请人：——

  公开号：US20030069269A1

  公开（公告）日：2003-04-10

  New tropane analogs that bind to monoamine transporters are described, particularly, 8-aza, 8carbo and 8-oxo tropanes having 6- or 7- substituents. The compounds of the present invention can be racemic, pure R-enantiomers, or pure S-enantiomers Certain preferred compounds of the present invention have a high selectivity for the DAT versus the SERT. Also described are pharmaceutical therapeutic compositions comprising the compounds formulated in a pharmaceutically acceptable carrier and a method for inhibiting 5-hydroxy-tryptamine reuptake of a monoamine transporter by contacting the monoamine transporter with a 5-hydroxytryptamine reuptake inhibiting amount of a compound of the present invention. Preferred monoamine transporters for the practice of the present invention include the dopamine transporter, the serotonin transporter and the norepinephrine transporter.

  本文描述了能够结合单胺转运体的新的范围内的替罗巴因类似物，特别是具有6-或7-取代基的8-氮杂、8-碳基和8-氧杂替罗巴因。本发明的化合物可以是外消旋体、纯R对映体或纯S对映体。本发明的某些优选化合物具有高选择性，能够选择性地结合到多巴胺转运体而不是选择性地结合到血清素转运体。此外，本文还描述了制备药物治疗组合物的方法，该组合物包括以药学可接受的载体为基础的化合物，并通过将本发明的化合物与单胺转运体接触来抑制5-羟色胺的再摄取。本发明实施的优选单胺转运体包括多巴胺转运体、血清素转运体和去甲肾上腺素转运体。
• TROPANE ANALOGS AND METHODS FOR INHIBITION OF MONOAMINE TRANSPORT
  申请人：ORGANIX, INC.

  公开号：EP0996619A1

  公开（公告）日：2000-05-03
• US5948933A
  申请人：——

  公开号：US5948933A

  公开（公告）日：1999-09-07