2β-carbomethoxy-3β-(3-iodophenyl)tropane | 143966-02-3

• 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-iodophenyl)tropane
• 英文别名: 3β-(3'-iodophenyl)tropane-2β-carboxylic acid methyl ester；RTI 92；methyl (1R,2S,3S,5S)-3-(3-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 143966-02-3
• 化学式: C₁₆H₂₀INO₂
• 分子量: 385.245
• InChiKey: XUBVUMLIQBPHGD-YJNKXOJESA-N

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-iodophenyl)tropane 在 1-氯乙基氯甲酸酯 、 甲醇 作用下， 以 1,2-二氯乙烷 为溶剂， 以62%的产率得到YP 256
  参考文献：
  名称：

  Synthesis and monoamine transporter affinity of 3′-analogs of 2-β-carbomethoxy-3-β-(4′-iodophenyl)tropane (β-CIT)

  摘要：

  The 3'-iodo positional isomer of 2-beta-carbomethoxy-3-beta-(4'-iodophenyl)tropane (beta-CIT) and other 3'-substituted analogs were synthesized and evaluated for binding to momoamine transporters in rat forebrain and membranes of cell lines selectively expressing human transporter genes. All 3'-substituted compounds displayed affinity for both serotonin (SERT) and dopamine (DAT), but much less for norepinephrine transporters (NET), with selectivity for rat (r) or human (h) SERT over NET, but only 3'-iodo-substituted phenyltropanes showed selectivity for SERT versus DAT. The 3'-iodo, N-methyl analog of beta-CIT (7) displayed 9-fold selectivity and high affinity for hSERT (K-i = 9.6 nM) over hDAT (K-i = 279 nM), and its nor-congener (8) showed even higher hSERT potency (K-i = 1.2 nM) and selectivity over DAT (415-fold). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.02.043
• 作为产物：
  描述：

  (1R,2S,3S,5S)-8-Methyl-3-(3-trimethylsilanyl-phenyl)-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester 在 silver tetrafluoroborate 、 碘 作用下， 以 甲醇 为溶剂， 以60%的产率得到2β-carbomethoxy-3β-(3-iodophenyl)tropane
  参考文献：
  名称：

  Synthesis and monoamine transporter affinity of 3′-analogs of 2-β-carbomethoxy-3-β-(4′-iodophenyl)tropane (β-CIT)

  摘要：

  The 3'-iodo positional isomer of 2-beta-carbomethoxy-3-beta-(4'-iodophenyl)tropane (beta-CIT) and other 3'-substituted analogs were synthesized and evaluated for binding to momoamine transporters in rat forebrain and membranes of cell lines selectively expressing human transporter genes. All 3'-substituted compounds displayed affinity for both serotonin (SERT) and dopamine (DAT), but much less for norepinephrine transporters (NET), with selectivity for rat (r) or human (h) SERT over NET, but only 3'-iodo-substituted phenyltropanes showed selectivity for SERT versus DAT. The 3'-iodo, N-methyl analog of beta-CIT (7) displayed 9-fold selectivity and high affinity for hSERT (K-i = 9.6 nM) over hDAT (K-i = 279 nM), and its nor-congener (8) showed even higher hSERT potency (K-i = 1.2 nM) and selectivity over DAT (415-fold). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.02.043

文献信息

• Synthesis, Ligand Binding, and QSAR (CoMFA and Classical) Study of 3.beta.-(3'-Substituted phenyl)-, 3.beta.-(4'-Substituted phenyl)-, and 3.beta.-(3',4'-Disubstituted phenyl)tropane-2.beta.-carboxylic Acid Methyl Esters
  作者：F. Ivy Carroll、S. Wayne Mascarella、Michael A. Kuzemko、Yigong Gao、Philip Abraham、Anita H. Lewin、John W. Boja、Michael J. Kuhar

  DOI：10.1021/jm00044a007

  日期：1994.9

  Several new 3 beta-(4'-substituted phenyl)-, 3-beta-(3'-substituted phenyl)-, and 3 beta-(3',4'-disubstituted phenyl)tropane-2 beta-carboxylic acid methyl esters were prepared and assayed for inhibition of [3H]WIN 35,428 binding to the dopamine transporter. The 3 beta-(3',4'-dichloro) and 3 beta-(4'-chloro-3'-methyl) analogues (2w and 2y; RTI-111 and RTI-112, respectively) with IC50 values of 0.79

  几种新的3β-（4'-取代的苯基）-，3-β-（3'-取代的苯基）-和3β-（3'，4'-二取代的苯基）tropane-2β-羧酸甲酯制备并测定对[3H] WIN 35,428与多巴胺转运蛋白结合的抑制作用。3个beta-（3'，4'-dichloro）和3个beta-（4'-chloro-3'-methyl）类似物（分别为2w和2y; RTI-111和RTI-112），IC50值为0.79和0.81 nM显示最高亲和力。研究了从经典和比较分子场分析（CoMFA）方法获得的定量构效关系（QSAR）模型对合理药物设计的贡献。CoMFA模型是使用具有SYBYL默认值的空间和静电势导出的，而经典模型是根据pi和MR参数导出的。使用12个化合物的训练集，两个模型都用于预测训练集内外的化合物的结合亲和力。CoMFA研究为影响与DA转运蛋白结合的空间和静电因素提供了新的见解，并为我们最初的发现提供了额
• 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.
• 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.