(1R)-3α-phenyl-2β-(3-methyl-[1,2,4]oxadiazole-5-yl)tropane | 146726-47-8

• 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: (1R)-3α-phenyl-2β-(3-methyl-[1,2,4]oxadiazole-5-yl)tropane
• 英文别名: 3α-phenyl-2β-(3'-methyl-1',2',4'-oxadiazol-5'-yl)tropane；3α-phenyl-2β-(3'-methyl-1,2,4-oxadiazole-5'-yl)tropane；3-methyl-5-[(1R,2S,3R,5S)-8-methyl-3-phenyl-8-azabicyclo[3.2.1]octan-2-yl]-1,2,4-oxadiazole
• CAS: 146726-47-8
• 化学式: C₁₇H₂₁N₃O
• 分子量: 283.373
• InChiKey: QSHBOMWRGOGQOF-JONQDZQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R)-3α-phenyl-2β-(3-methyl-[1,2,4]oxadiazole-5-yl)tropane 在 盐酸 、 nickel boride 、 碘 、 silver trifluoromethanesulfonate 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 生成 3α-(4-iodophenyl)tropane-2β-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis and biological evaluation of 2β,3α-(substituted phenyl)nortropanes as potential norepinephrine transporter imaging agents

  摘要：

  A series of 2 beta,3 alpha-(substituted phenyl)nortropanes was synthesized and evaluated in vitro for human monoamine transporters. All compounds studied in this series exhibited nanomolar potency for the norepinephrine transporter (NET). Radiolabeling and nonhuman primate microPET brain imaging studies were performed with the most promising compound, [C-11]1, to determine its utility as a NET imaging agent. Despite high in vitro affinity for the human NET, the high uptake of [C-11]1 in the caudate and putamen excludes its use as an in vivo PET imaging agent for the NET. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.056
• 作为产物：
  描述：

  RTI 87 在 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 (1R)-3α-phenyl-2β-(3-methyl-[1,2,4]oxadiazole-5-yl)tropane
  参考文献：
  名称：

  Synthesis and cocaine receptor affinities of 3-phenyl-2-(3′-methyl-1,2,4-oxadiazole-5′-yl)tropane isomers

  摘要：

  本研究报告了从天然（−）可卡因衍生的所有四个异构体3-苯基-2-(3-甲基-1,2,4-噻唑-5-基)托烷的合成及其在可卡因受体的结合亲和力。

  DOI：

  10.1039/c39930000044

文献信息

• Dopamine transporter imaging ligand
  申请人：Research Triangle Institute

  公开号：US06358492B1

  公开（公告）日：2002-03-19

  The 3&agr; isomer of RTI-55, RTI-352, is an effective in vivo binding ligand that reflects greater selectivity for the dopamine transporter than is observed with RTI-55. In addition, there is also a more rapid achievement of apparent equilibrium in the striatal-to-cerebellar ratio (compared to RTI-55) as the ratio peaks at about 30 min and is maintained for about 20 min thereafter. Such apparent equilibrium is useful in developing an approach to measuring the number of dopamine transporters present in tissues. Moreover, these results indicate that the utilization of 3&agr; isomers of a variety of 3&bgr;-(substituted phenyl)tropanes will result in greater selectivity for dopamine transporters and a more rapid of achievement of apparent equilibrium.

  RTI-55的3α异构体RTI-352是一种有效的体内结合配体，反映出对多巴胺转运体的更大选择性，这种选择性比RTI-55观察到的要高。此外，与RTI-55相比，在纹状体与小脑比率中也更快地达到明显的平衡状态，比率在约30分钟时达到峰值，此后约维持20分钟。这种明显的平衡状态有助于开发一种测量组织中多巴胺转运体数量的方法。此外，这些结果表明，利用各种3β-(取代苯基)曲梯酮的3α异构体将导致更高的多巴胺转运体选择性和更快的明显平衡状态的实现。
• 3-Aryl-2-(3'-substituted-1',2',4'-oxadiazol-5'-yl)tropane analogs of cocaine: affinities at the cocaine binding site at the dopamine, serotonin, and norepinephrine transporters
  作者：F. Ivy Carroll、Jeffrey L. Gray、Philip Abraham、Michael A. Kuzemko、Anita H. Lewin、John W. Boja、Michael J. Kuhar

  DOI：10.1021/jm00072a007

  日期：1993.10

  Previous studies have shown that 3 beta-(substituted phenyl)tropan-2 beta-carboxylic acid esters possess high affinity for the cocaine binding site on the dopamine transporter both in vitro and in vivo and inhibit dopamine uptake in vitro. Since 1,2,4-oxadiazoles are excellent bioisosteres of ester groups, we have prepared several 3 beta-(substituted phenyl)-2 beta-(3-substituted 1',2',4'-oxadiazol-5'-yl)tropanes

  先前的研究表明，3种β-（取代的苯基）tropan-2β-羧酸酯在体外和体内对多巴胺转运蛋白上的可卡因结合位点均具有高亲和力，并在体外抑制多巴胺的摄取。由于1,2,4-恶二唑是优异的酯基生物等排体，我们制备了3个3-β-（取代的苯基）-2β-（3-取代的1'，2'，4'-恶二唑-5'-基）托烷（5b-h）和（1R，5S）-3苯基-2-（3-甲基-1'，2'，4'-恶二唑-5'-基）托烷的所有四个立体异构体（5a和6-8 ）。3苯基苯基-2-α-（3'-甲基-1'，2'，4'-恶二唑）异构体7是通过向（1R，5S）-2-（3'-甲基-1′，2′，4′-恶二唑-5-基）-8-甲基-8-氮杂双环[3.2.1]辛-2-烯（11）。获得了在多巴胺，5-羟色胺和去甲肾上腺素转运蛋白上5a-h和6-8的结合亲和力。通常，这些生物甾体对多巴胺转运蛋白的效力与其母体酯相似。3 beta-（4'-氯苯基）-2
• Monoamine Transporter Binding, Locomotor Activity, and Drug Discrimination Properties of 3-(4-Substituted-phenyl)tropane-2-carboxylic Acid Methyl Ester Isomers
  作者：F. Ivy Carroll、Scott P. Runyon、Philip Abraham、Hernan Navarro、Michael J. Kuhar、Gerald T. Pollard、James L. Howard

  DOI：10.1021/jm0401311

  日期：2004.12.1

  The monoamine transporter binding properties, gross behavior, and locomotor activity effects in mice and drug discrimination results in cocaine-trained rats of the 2beta3beta-, 2beta,3alpha-, 2alpha-,3beta-, and 2alpha-,3alpha-isomers of several 3-(4-substituted-phenyl)tropane carboxylic acid methyl esters were compared (2a-f, 3a-f, 4a-f, and 5b,c). The 2beta,3beta-isomer showed the highest affinity for the dopamine transporter (DAT), and the 2beta,3alpha-isomer showed the next highest affinity. The order of potency for the 2beta,3beta-isomer is 4'-chloro (2c) = 4'-iodo (2e) > 4'-bromo (2d) = 4'-methyl (2f) > 4'-fluoro (2b) > 4'-hydrogen (2a). In the case of the 2beta,3alpha-isomer, the order of affinity was 4'-bromo (3d) > 4'-iodo (3e) = 4'- chloro (3c) > 4'-methyl (3f) > 4'-fluoro (3b) > 4'-hydrogen (3a). The 4'-hydrogen, 4'-fluoro, and 4'-methyl 2alpha,3beta-isomers, 4a, 4b, and 4f, had the lowest affinity for the DAY While most of the compounds showed their highest affinity at the DAT, none were selective relative to the other two monoamine transporters. In general, the 2alpha,3alpha- and 2alpha,3beta-isomers were more toxic (death and convulsions) than the 2beta,3beta- and 2beta,3alpha-isomers. With the exception of the 2(x,3a-isomers, all compounds produced the locomotor activity stimulation typical of dopaminergic drugs. The ED50 ranges for the 2beta,3beta- (2a-f), 2beta,3alpha- (3a-f), and 2alpha,3alpha-isomers (4a-f) in the locomotor assay were 0.1-1.2, 6.6-21.8, and 2.4-11.7 mg/kg, respectively. With the exception of the 2a,3a-isomer, all compounds generalized to cocaine. The 2beta,3beta-isomers were at least 10-fold more potent than cocaine and the other three sets of isomers in this test.
• Synthesis and cocaine receptor affinities of 3-phenyl-2-(3′-methyl-1,2,4-oxadiazole-5′-yl)tropane isomers
  作者：F. Ivy Carroll、Philip Abraham、Michael A. Kuzemko、Jeffrey L. Gray、Anita H. Lewin、John W. Boja、Michael J. Kuhar

  DOI：10.1039/c39930000044

  日期：——

  This study reports the synthesis and binding affinities at the cocaine receptor of all four isomers of 3-phenyl-2-(3-methyl-1,2,4-oxadiazole-5-yl)tropane derivable from natural (–)-cocaine

  本研究报告了从天然（−）可卡因衍生的所有四个异构体3-苯基-2-(3-甲基-1,2,4-噻唑-5-基)托烷的合成及其在可卡因受体的结合亲和力。
• Synthesis and biological evaluation of 2β,3α-(substituted phenyl)nortropanes as potential norepinephrine transporter imaging agents
  作者：Fanxing Zeng、Jeffrey S. Stehouwer、Nachwa Jarkas、Ronald J. Voll、Larry Williams、Vernon M. Camp、John R. Votaw、Michael J. Owens、Clinton D. Kilts、Charles B. Nemeroff、Mark M. Goodman

  DOI：10.1016/j.bmcl.2007.03.056

  日期：2007.6

  A series of 2 beta,3 alpha-(substituted phenyl)nortropanes was synthesized and evaluated in vitro for human monoamine transporters. All compounds studied in this series exhibited nanomolar potency for the norepinephrine transporter (NET). Radiolabeling and nonhuman primate microPET brain imaging studies were performed with the most promising compound, [C-11]1, to determine its utility as a NET imaging agent. Despite high in vitro affinity for the human NET, the high uptake of [C-11]1 in the caudate and putamen excludes its use as an in vivo PET imaging agent for the NET. (C) 2007 Elsevier Ltd. All rights reserved.