(S)-alloecgonine methyl ester | 149110-83-8

• 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: (S)-alloecgonine methyl ester
• CAS: 149110-83-8
• 化学式: C₁₀H₁₇NO₃
• 分子量: 199.25
• InChiKey: QIQNNBXHAYSQRY-XGEHTFHBSA-N

物化性质

• 沸点：
  305.8±37.0 °C(Predicted)
• 密度：
  1.181±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.0
• 重原子数：
  14.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  49.77
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (S)-alloecgonine methyl ester 在 三氯氧磷 作用下， 生成 (+/-)-Win 35140
  参考文献：
  名称：

  可卡因识别位点的对映选择性：（1S）-和（1R）-2 beta-carbomethoxy-3 beta-（4-iophenylphenyl）tropane（beta-CIT）与单胺转运蛋白的结合。

  摘要：

  DOI：

  10.1021/jm00065a014
• 作为产物：
  描述：

  托品酮 在 platinum(IV) oxide 盐酸 、 正丁基锂 、 水 、 氢气 、 (R)-(-)-N-新戊基-1-苯基-2-(1-吡啶烷)乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 为溶剂， -78.0~20.0 ℃ 、344.74 kPa 条件下， 反应 117.0h， 生成 (S)-alloecgonine methyl ester
  参考文献：
  名称：

  Structure−Activity Relationship Comparison of (S)-2β-Substituted 3α-(Bis[4-fluorophenyl]methoxy)tropanes and (R)-2β-Substituted 3β-(3,4-Dichlorophenyl)tropanes at the Dopamine Transporter

  摘要：

  Extensive structure-activity relationships at the dopamine transporter (DAT) have been developed around two classes of tropane-based ligands. Opposing stereoselectivity and divergent structural requirements for optimal DAT binding suggest that these tropane-based DAT inhibitors may not access identical binding domains. To further investigate this hypothesis, a series of (S)-2beta-carboalkoxy-3alpha-(bis[4-fluorophenyl]methoxy)tropanes (11a-f, 13-16) and their identically (R)-2beta-substituted 3beta-(3,4-dichlorophenyl)tropanes (3, 5a-d) were prepared and evaluated for binding at the DAT and for inhibition of [H-3]dopamine uptake in rat brain. These studies showed that most of the identically 2-carboalkoxy-substituted analogues, within the two classes of compounds, bind with high affinity to DAT (K-i = 5.5 - 100 nM), albeit with opposite stereochemistry. However, the larger azido- (15) and isothiocyanato- (16) (S)-2beta-carbophenylethoxy-3alpha-(bis [4-fluorophenyl] methoxy)tropanes demonstrated a significant decrease in DAT binding potency (IC50 = 210 and 537 nM, respectively), suggesting that the DAT does not tolerate 2-position steric bulk in the benztropine class, as it does with the 2-substituted 3-aryltropanes. In addition, binding affinities at the serotonin transporter, norepinephrine transporter, and muscarinic receptors were evaluated and compared for compounds 2, 3, 11a-e, and 13. Together, the binding profiles across these systems demonstrated significant differences between these two classes of tropane-based ligands, which may be exploited toward the discovery of a cocaine-abuse pharmacotherapeutic.

  DOI：

  10.1021/jm0300375

文献信息

• Synthesis and ligand binding of cocaine isomers at the cocaine receptor
  作者：F. Ivy Carroll、Anita H. Lewin、Philip Abraham、Karol Parham、John W. Boja、Michael J. Kuhar

  DOI：10.1021/jm00107a003

  日期：1991.3

  transporter has been found to be stereoselective. Thus, the seven possible stereoisomers of (-)-cocaine have been synthesized and found to inhibit [3H]-2 beta-carbomethoxy-3 beta-(4-fluoro-phenyl)tropane [( 3H]WIN 35,428) with potencies ranging from 1/60 to 1/600 of that of (-)-cocaine. The synthesis and characterization of all new compounds is presented.

  已经发现多巴胺转运蛋白上的可卡因结合位点是立体选择性的。因此，已经合成了（-）-可卡因的七个可能的立体异构体，并发现其抑制[3H] -2β-羰甲氧基-3β-（4-氟-苯基）托烷[（3H] WIN 35,428）的能力范围为（-）-可卡因的1/60至1/600。介绍了所有新化合物的合成和表征。
• Structure−Activity Relationship Studies on a Novel Series of (<i>S</i>)-2β-Substituted 3α-[Bis(4-fluoro- or 4-chlorophenyl)methoxy]tropane Analogues for in Vivo Investigation
  作者：Mu-Fa Zou、Jianjing Cao、Theresa Kopajtic、Rajeev I. Desai、Jonathan L. Katz、Amy Hauck Newman

  DOI：10.1021/jm060762q

  日期：2006.10.1

  yet inhibition of dopamine uptake potency remained comparably high (IC(50) range = 1.5-2.5 nM). Interestingly, the 4'-Cl analogue (+/-)-6 substituted less in rats trained to discriminate cocaine than the 4'-F analogue (+/-)-5. These studies demonstrate that manipulation of the 2-, N-, and 3-position substituents in the 3alpha-(diphenylmethoxy)tropane class of dopamine uptake inhibitors can result in ligands

  通常，基于3α-​​（二苯甲氧基）托烷（苯并卓平）的多巴胺摄取抑制剂在精神兴奋剂滥用模型中未显示出可卡因样的药理活性，因此已被提议作为治疗可卡因成瘾的潜在药物。然而，发现一些（S）-2-碳烷氧基取代的3α-[双（4-氟苯基）甲氧基]托烷类似物可刺激运动能力并替代受过训练的可卡因识别对象，这表明了2-位取代基的作用。调解这些可卡因样的行为。在这里，我们描述了一系列新型的N和2-取代的3α-[双（4-氟-或4-氯苯基）甲氧基]托烷类似物的合成。这些类似物大多数都表现出与多巴胺转运蛋白的高亲和力结合（DAT； K（i）= 1.8-40 nM），和其他单胺转运蛋白和毒蕈碱M（1）受体的选择性。当（S）-2-羰基烷氧基取代基被（S）-2-乙烯基取代时，所得类似物11在该系列（K（i）= 1.81 nM）中显示出最高的DAT结合亲和力，其DAT选择性优于血清素转运蛋白（ SERT； 989倍），去甲肾上腺素转运蛋白（NET；
• The Three-Dimensional Structures of the Cocaines. II. Racemic Allococaine and Racemic Allopseudococaine
  作者：STEPHEN P. FINDLAY

  DOI：10.1021/jo01092a040

  日期：1959.10
• Enantioselective synthesis of S-(+)-2β-carboalkoxy-3α-[bis(4-fluorophenyl)methoxy]tropanes as novel probes for the dopamine transporter
  作者：Mu-Fa Zou、Gregory E Agoston、Yuri Belov、Theresa Kopajtic、Jonathan L Katz、Amy Hauck Newman

  DOI：10.1016/s0960-894x(02)00155-5

  日期：2002.5

  Synthesis of a series of pure S-(+)-2beta-carboalkoxy-3alpha-[bis(4-fluotophenyl)metlioxy]tropanes (>99% ee) was achieved by employing a chiral amine-induced asymmetric reaction of tropinone with methyl cyanoformate as the key step. In this series, all of the S-(+)-enantiomers were 2-fold more potent than their racemic mixtures and all displayed high-affinity binding for DAT (K-i - 13-40 nM). These data support previous findings of significant divergence in structural requirements for high-affinity DAT binding among tropane-based inhibitors. Furthermore, the 2-substituent in the 3alpha-[bis(4-fluorophenyl)methoxy]tropane series is well tolerated at the DAT but not at SERT (K-i = 690-2040 nM), or muscarinic M-1 receptors (K-i - 133-4380 nM) resulting in highly selective DAT ligands that may provide new leads toward a cocaine-abuse therapeutic. (C) 2002 Elsevier Science Ltd. All rights reserved.
• The Discovery of an Unusually Selective and Novel Cocaine Analog: Difluoropine. Synthesis and Inhibition of Binding at Cocaine Recognition Sites
  作者：Peter C. Meltzer、Anna. Y. Liang、Bertha. K. Madras

  DOI：10.1021/jm00039a014

  日期：1994.6

  Cocaine is a stimulant drug with a high abuse liability. Although it inhibits several monamine transporters in the mammalian brain, its primary mechanism of action has been ascribed to its inhibition of the dopamine transporter. The synthesis, characterization, and receptor binding properties of all eight isomers of a unique tropane analog, 2-carbomethoxy-3-[bis(4-fluorophenyl)methoxy]tropane is described. In addition, we report that the S-enantiomer, (S)-(+)-2 beta-carbomethoxy-3 alpha-[bis(4-fluorophenyl)methoxy]tropane, Difluoropine, is a potent (IC50 10.9 nM) and selective (324 [DA/5HT]) ligand for the dopamine transporter.