2β-carbomethoxy-3β-(3-bromophenyl)tropane | 146725-31-7

• 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: 2β-carbomethoxy-3β-(3-bromophenyl)tropane
• 英文别名: methyl (1R,2S,3S,5S)-3-(3-bromophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 146725-31-7
• 化学式: C₁₆H₂₀BrNO₂
• 分子量: 338.244
• InChiKey: ORJOVSLDGBGQAL-YJNKXOJESA-N

物化性质

• 沸点：
  389.1±42.0 °C(predicted)
• 密度：
  1.342±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2β-carbomethoxy-3β-(3-bromophenyl)tropane 在 1,4-二氧六环 、 水 作用下， 反应 16.0h， 以68%的产率得到3β-(3'-bromophenyl)tropane-2β-carboxylic acid
  参考文献：
  名称：

  氟 18 标记的 2beta-carbo(fluoroalkoxy)-3beta-(3'-((Z)-2-haloethenyl)phenyl)nortropanes 的合成、放射合成和生物学评价：用于血清素转运蛋白体内成像的候选放射性配体正电子发射断层扫描。

  摘要：

  间卤乙烯氟烷基酯去甲托烷 1-4 合成为血清素转运蛋白 (SERT) 的配体，用作正电子发射断层扫描 (PET) 成像剂。体外竞争结合测定表明 1-4 对 SERT 具有高亲和力（K(i) 值 = 0.3-0.4 nM），并且对多巴胺和去甲肾上腺素转运蛋白（DAT 和 NET）上的 SERT 具有选择性。[(18)F]1-[(18)F]4 麻醉食蟹猴的 MicroPET 成像表明，所有四种示踪剂的行为相似，在 45-55 分钟后达到富含 SERT 的大脑区域的峰值吸收，然后是稳定的冲刷。对 [(18)F]1 进行的清醒猴子研究表明，[(18)F]1 的摄取不受麻醉影响。用 SERT 配体 15 取代 [(18)F]1-[(18)F]4 的 Chase 研究，

  DOI：

  10.1021/jm800781a
• 作为产物：
  描述：

  古卡因 在 盐酸 、 三氯氧磷 作用下， 以 乙醚 为溶剂， 反应 2.0h， 生成 2β-carbomethoxy-3β-(3-bromophenyl)tropane
  参考文献：
  名称：

  Substituted 3-phenyltropane analogs of cocaine: synthesis, inhibition of binding at cocaine recognition sites, and positron emission tomography imaging

  摘要：

  It is now accepted that (-)-cocaine binds to specific recognition sites associated with monoamine transporters in the mammalian brain. In this study, several analogs of 3beta-phenyltropane-2beta-carboxylic acid methyl ester were prepared and their potency for inhibiting the binding of [H-3]-3beta-(4-fluorophenyl)tropane-2beta-carboxylic acid methyl ester to primate caudate-putamen was evaluated. The synthesis and binding affinity of 3beta-(3,4-dichlorophenyl)tropane-2beta-carboxylic acid methyl ester, one of the most potent cocaine congeners yet reported, is presented. The feasibility of synthesizing high-affinity ligands for cocaine recognition sites and their suitability as PET imaging ligands for cocaine receptors in vivo is demonstrated.

  DOI：

  10.1021/jm00059a010

文献信息

• Cocaine analogues and their use as cocaine drug therapies and
  申请人：President and Fellows of Harvard College

  公开号：US05506359A1

  公开（公告）日：1996-04-09

  Disclosed are benztropine and CFT analogs useful for imaging of cocaine receptors and treatment of cocaine abuse. Also disclosed are analogs useful for imaging and treatment of Parkinson's disease.

  揭示了对可卡因受体进行成像和治疗可卡因滥用有用的苯丙替品和CFT类似物。还揭示了对帕金森病进行成像和治疗有用的类似物。
• Synthesis, Radiosynthesis, and Biological Evaluation of Carbon-11 Labeled 2β-Carbomethoxy-3β-(3‘-((<i>Z</i>)-2-haloethenyl)phenyl)nortropanes:  Candidate Radioligands for in Vivo Imaging of the Serotonin Transporter with Positron Emission Tomography
  作者：Jeffrey S. Stehouwer、Nachwa Jarkas、Fanxing Zeng、Ronald J. Voll、Larry Williams、Michael J. Owens、John R. Votaw、Mark M. Goodman

  DOI：10.1021/jm060641q

  日期：2006.11.1

  '-((Z)-2-iodoethenyl)phenyl)nortropane (mZIENT, 1) and 2beta-carbomethoxy-3beta-(3'-((Z)-2-bromoethenyl)phenyl)nortropane (mZBrENT, 2) were synthesized and evaluated for binding to the human serotonin, dopamine, and norepinephrine transporters (SERT, DAT, and NET, respectively) using transfected cells. Both 1 and 2 have a high affinity for the SERT (Ki=0.2 nM) and are approximately 160 times more selective

  2beta-羰甲氧基-3beta-（3'-（（（Z）-2-碘乙烯基）苯基）降冰片烷（mZIENT，1）和2beta-羰甲氧基-3beta-（3'-（（（Z）-2-溴乙烯基）苯基） （mZBrENT，2）合成并使用转染的细胞评估与人血清素，多巴胺和去甲肾上腺素转运蛋白（分别为SERT，DAT和NET）的结合。1和2对SERT的亲和性都很高（Ki = 0.2 nM），对SERT的选择性是DAT的160倍左右。化合物2对NET的亲和力比1高得多，这可能是卤素原子的大小和电负性不同的结果。在具有[11C] 1和[11C] 2的非人类灵长类动物中的MicroPET成像表明，两种示踪剂在体内的行为相似，在富含SERT的大脑区域中观察到了高吸收，并且在注射后约55分钟内达到了峰值吸收。对西酞普兰和哌醋甲酯的追踪研究表明，这种摄取是优先结合SERT的结果。
• US5506359A
  申请人：——

  公开号：US5506359A

  公开（公告）日：1996-04-09
• [EN] COCAINE ANALOGUES AND THEIR USE AS COCAINE DRUG THERAPIES AND THERAPEUTIC AND IMAGING AGENTS FOR NEURODEGENERATIVE DISORDERS<br/>[FR] ANALOGUES DE COCAINE ET LEUR EMPLOI COMME THERAPIE ANTI-COCAINE ET AGENTS THERAPEUTIQUES ET D'IMAGERIE DE TROUBLES NEURODEGENERATIFS
  申请人：PRESIDENT AND FELLOWS OF HARVARD COLLEGE

  公开号：WO1994004146A1

  公开（公告）日：1994-03-03

  (EN) Disclosed are benztropine and CFT analogs useful for imaging of cocaine receptors and treatment of cocaine abuse. Also disclosed are analogs useful for imaging and treatment of Parkinson's disease.(FR) L'invention concerne des analogues de benztropine et de CFT (2$g(b)-carbométhoxy-3$g(b)-(4-fluorophényle)tropane) utiles dans l'imagerie de récepteurs de cocaïne et le traitement de la consommation de cocaïne. L'invention concerne également des analogues utiles dans l'imagerie et le traitement de la maladie de Parkinson.
• Substituted 3-phenyltropane analogs of cocaine: synthesis, inhibition of binding at cocaine recognition sites, and positron emission tomography imaging
  作者：P. C. Meltzer、A. Y. Liang、A. L. Brownell、D. R. Elmaleh、B. K. Madras

  DOI：10.1021/jm00059a010

  日期：1993.4

  It is now accepted that (-)-cocaine binds to specific recognition sites associated with monoamine transporters in the mammalian brain. In this study, several analogs of 3beta-phenyltropane-2beta-carboxylic acid methyl ester were prepared and their potency for inhibiting the binding of [H-3]-3beta-(4-fluorophenyl)tropane-2beta-carboxylic acid methyl ester to primate caudate-putamen was evaluated. The synthesis and binding affinity of 3beta-(3,4-dichlorophenyl)tropane-2beta-carboxylic acid methyl ester, one of the most potent cocaine congeners yet reported, is presented. The feasibility of synthesizing high-affinity ligands for cocaine recognition sites and their suitability as PET imaging ligands for cocaine receptors in vivo is demonstrated.