3β-(3'-iodo-4'-aminophenyl)tropane-2β-carboxylic acid methyl ester dihydrochloride | 140633-57-4

• 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: 3β-(3'-iodo-4'-aminophenyl)tropane-2β-carboxylic acid methyl ester dihydrochloride
• 英文别名: 3β-(3-iodo-4-aminophenyl)tropan-2β-carboxylic acid methyl ester dihydrochloride
• CAS: 140633-57-4
• 化学式: C₁₆H₂₁IN₂O₂*2ClH
• 分子量: 473.181
• InChiKey: LSTJCTNVHGJZAG-LZRDFDPJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.03
• 重原子数：
  22.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.56
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3β-(3'-iodo-4'-aminophenyl)tropane-2β-carboxylic acid methyl ester dihydrochloride 在 sodium azide 、 溶剂黄146 、 sodium nitrite 作用下， 生成 3β-(3-iodo-4-azidophenyl)tropan-2β-carboxylic acid methyl ester
  参考文献：
  名称：

  Probes for the cocaine receptor. Potentially irreversible ligands for the dopamine transporter

  摘要：

  Several potentially irreversible ligands (i.e., wash-resistant binding inhibitors) for the cocaine receptor site on the dopamine transporter, derived from (-)-cocaine or 3-beta-phenyltropan-2-beta-carboxylic acid methyl ester (WIN 35,065-2), were prepared and shown to produce wash-resistant inhibition of [H-3]-3-beta-(p-fluorophenyl)tropan-2-beta-carboxylic acid methyl ester ([H-3]WIN 35,428) binding. All the compounds prepared had the same absolute configuration as cocaine; they include analogues possessing chemically reactive groups such as the isothiocyanato and bromoacetamido as well as photoactive azido groups. The potentially irreversible ligands, as well as all the intermediates prepared in this study, were evaluated for their ability to inhibit the binding of [H-3]WIN 35,428 in coincubation experiments. Of the potentially irreversible ligands, 3-beta-(p-chlorophenyl)tropan-2-beta-carboxylic acid 2-[p-(bromoacetamido)phenyl]ethyl ester (6c) had the highest apparent potency. The potentially irreversible ligands were also preincubated, and inhibition of [H-3]WIN 35,428 binding was determined both before and after washing the ligand-exposed tissues. The most effective ligands in this regard were 3-beta-(3-iodo-4-azidophenyl)tropan-2-beta-carboxylic acid methyl ester (5) and 3-beta-(p-chlorophenyl)tropan-2-beta-carboxylic acid 2-(3-iodo-4-azidophenyl)ethyl ester (6d). The structure-activity relationships of these data are discussed.

  DOI：

  10.1021/jm00088a017
• 作为产物：
  描述：

  3β-[4'-aminophenyl]tropan-2β-carboxylic acid methyl ester 在 盐酸 作用下， 以 glacial AcOH 为溶剂， 以140 mg (29%)的产率得到3β-(3'-iodo-4'-aminophenyl)tropane-2β-carboxylic acid methyl ester dihydrochloride
  参考文献：
  名称：

  Cocaine receptor binding ligands

  摘要：

  具有高亲和力的化合物在大脑中特定可卡因受体合成中作为中间体有用，其化学式为##STR1##其中R为(CH.sub.2).sub.n CH.sub.2 Y，Y为H或F，X为药用可接受的阴离子，Sn(R.sup.1, R.sup.2, R.sup.3)为邻位、间位或对位，R.sup.1, R.sup.2, R.sup.3独立地为1-6个碳原子的烷基，n为0-5的整数。

  公开号：

  US05736123A1

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