2-O-methyl 8-O-(2,2,2-trichloroethyl) (1R,2S,3S,5S)-3-(4-iodophenyl)-8-azabicyclo[3.2.1]octane-2,8-dicarboxylate | 156496-01-4

• 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: 2-O-methyl 8-O-(2,2,2-trichloroethyl) (1R,2S,3S,5S)-3-(4-iodophenyl)-8-azabicyclo[3.2.1]octane-2,8-dicarboxylate
• CAS: 156496-01-4
• 化学式: C₁₈H₁₉Cl₃INO₄
• 分子量: 546.617
• InChiKey: BFMDMAQBDWQNTF-YJNKXOJESA-N

物化性质

• 沸点：
  528.2±50.0 °C(Predicted)
• 密度：
  1.675±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-O-methyl 8-O-(2,2,2-trichloroethyl) (1R,2S,3S,5S)-3-(4-iodophenyl)-8-azabicyclo[3.2.1]octane-2,8-dicarboxylate 在 bis-triphenylphosphine-palladium(II) chloride 、 正丁基锂 、 溶剂黄146 、 zinc(II) chloride 、 锌 作用下， 反应 26.0h， 生成 (1R,2S,3S,5S)-3-(4-Isopropenyl-phenyl)-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis and Transporter Binding Properties of 3β-(4‘-Alkyl-, 4‘-alkenyl-, and 4‘-alkynylphenyl)nortropane-2β-carboxylic Acid Methyl Esters:  Serotonin Transporter Selective Analogs

  摘要：

  New methods for the synthesis of 3 beta-(4'-alkyl-, 4'-alkenyl-, and 4'-alkynylphenyl)nortropane-2 beta-carboxylic acid methyl esters 2-4, respectively, were developed. These methods involved coupling of the appropriate organometallic reagents to 3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (6a, RTI-55) or to an N-protected derivative of 6a followed by N-demethylation or removal of the protecting group. Some analogs were prepared by catalytic reduction of the alkene and alkyne analogs 3 and 4 or by isomerization of the alkenes 3. The analogs 2-4 were evaluated for inhibition of radioligand binding to the serotonin (5-HT), dopamine (DA), and norepinephrine (NE) transporters. 3 beta-(4'-Isopropenyl- and 4'-cis-propenylphenyl)nortropane-2 beta-carboxylic acid methyl esters (3b,d), which possessed IC50 values of 0.6 and 1.15 nM, respectively, were the most potent analogs at the 5-HT transporter, and with NE/5-HT IC50 ratios of 240 and 128 nM, respectively, they were selective for the 5-HT relative to the NE transporter. Since interaction with the serotonin transporter may modulate the pharmacological effects resulting from binding to the dopamine transporter, 3 beta-(4'-isopropenylphenyl)tropane-2 beta-carboxylic acid methyl ester (11b) which has good affinity for both the 5-HT and DA transporters but low affinity at the NE transporter may be useful for studying this interaction.

  DOI：

  10.1021/jm960409s
• 作为产物：
  描述：

  生成 2-O-methyl 8-O-(2,2,2-trichloroethyl) (1R,2S,3S,5S)-3-(4-iodophenyl)-8-azabicyclo[3.2.1]octane-2,8-dicarboxylate
  参考文献：
  名称：

  Chen; Kilts; Camp, Journal of labelled compounds and radiopharmaceuticals, 1999, vol. 42, # SUPPL. 1, p. S400-S402

  摘要：

  DOI：

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。
• Synthesis and monoamine transporter affinity of new 2β-carbomethoxy-3β-[aryl or heteroaryl]phenyltropanes
  作者：Gilles Tamagnan、David Alagille、Xing Fu、Nora S. Kula、Ross J. Baldessarini、Robert B. Innis、Ronald M. Baldwin

  DOI：10.1016/j.bmcl.2005.09.016

  日期：2006.1

  A series of 16 new 2 beta-carbomethoxy-3 beta-[aryl or heteroaryl]phenyltropane derivatives was synthesized and evaluated for binding to monoamine transporters. Most of the compounds exhibited nanomolar affinity for the serotonin transporter (SERT). Four compounds (29, 14, 11, and 10) presented a particularly attractive pharmacological profile, with very high SERT affinity (K-i 0.15-0.5 nM) and selectivity versus the dopamine transporter of 25- to 77-fold. (c) 2005 Elsevier Ltd. All rights reserved.
• Synthesis and monoamine transporter affinity of new 2β-carbomethoxy-3β-[4-(substituted thiophenyl)]phenyltropanes: discovery of a selective SERT antagonist with picomolar potency
  作者：Gilles Tamagnan、David Alagille、Xing Fu、Nora S. Kula、Ross J. Baldessarini、Robert B. Innis、Ronald M. Baldwin

  DOI：10.1016/j.bmcl.2004.12.014

  日期：2005.2

  Preparation of cocaine analogues has been aimed largely at development of stable compounds with high affinity and selectivity for the dopamine transporter (DAT). We now report the synthesis and monoamine transporter affinity of 10 new 2beta-carbomethoxy-3p-[4-(substituted thiophenyl)]phenyltropanes. Among these, compound 4b exhibited very high affinity for the serotonin transporter (SERT: K-i = 17 pM) and good selectivity over dopamine (DAT: 710-fold) and norepinephrine transporters (NET: 11,100-fold). (C) 2004 Elsevier Ltd. All rights reserved.
• 3β-(4-Ethyl-3-iodophenyl)nortropane-2β- carboxylic Acid Methyl Ester as a High-Affinity Selective Ligand for the Serotonin Transporter
  作者：Bruce E. Blough、Philip Abraham、Andrew C. Mills、Anita H. Lewin、John W. Boja、Ursula Scheffel、Michael J. Kuhar、F. Ivy Carroll

  DOI：10.1021/jm970492z

  日期：1997.11.1