5-p-tolyl-3,5-dihydro-2H-imidazo[2,1-a]isoindol-5-ol | 33184-37-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 5-p-tolyl-3,5-dihydro-2H-imidazo[2,1-a]isoindol-5-ol
• 英文别名: 5-p-tolyl-2,5-dihydro-3H-imidazo[2,1-a]isoindol-5-ol；5-(p-Tolyl)-5-hydroxy-2,3-dihydro-5H-imidazo<2,1-a>isoindol；2,3-Dihydro-5-(4-tolyl)-5H-imidazo<2,1-a>isoindol-5-ol；5-p-Tolyl-2,5-dihydro-3H-imidazo[2,1-a]isoindol-5-ol；5-(4-methylphenyl)-2,3-dihydroimidazo[1,2-b]isoindol-5-ol
• CAS: 33184-37-1
• 化学式: C₁₇H₁₆N₂O
• 分子量: 264.327
• InChiKey: OZANMDDPBVRVJW-UHFFFAOYSA-N

物化性质

• 熔点：
  208-209 °C (decomp)(Solv: N,N-dimethylformamide (68-12-2))
• 沸点：
  446.2±55.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  35.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  对甲基苯甲酸甲酯 、 2-苯基咪唑啉 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 9.0h， 以46%的产率得到5-p-tolyl-3,5-dihydro-2H-imidazo[2,1-a]isoindol-5-ol
  参考文献：
  名称：

  Mazindol Analogues as Potential Inhibitors of the Cocaine Binding Site at the Dopamine Transporter

  摘要：

  A series of mazindol. (2) and homomazindol (3) analogues with a variety of electron-donating and electron-withdrawing groups in the pendant aryl group and the benzo ring C, as well as H, methoxy, and alkyl groups replacing the hydroxyl group were synthesized, and their binding affinities at the dopamine transporter (DAT) on rat or guinea pig striatal. membranes were determined. Several active analogues were also evaluated for their ability to block uptake of DA, 5-HT, and NE and inhibit binding of [I-125] RTI-55 at HEK-hDAT, HEK-hSERT, and HEK-hNET cells. Mazindane (26) was found to be a pro-drug, oxidizing (5-H --> 5-OH) to mazindol on rat striatal membranes and HEk-hDAT cells. The 4',7,8-trichloro analogue (38) of mazindol was the I most potent and selective ligand. for HEK-hDAT cells (DAT K-i = 1.1 nM; SERT/DAT 1283 and NET/DAT = 38). Experimental results strongly favor the cyclic or ol tautomers of 2 and 3 to bind more, tightly at the DAT than the corresponding keto tautomers.

  DOI：

  10.1021/jm010302r

文献信息

• Binding of Mazindol and Analogs to the Human Serotonin and Dopamine Transporters
  作者：Kasper Severinsen、Heidi Koldsø、Katrine Almind Vinberg Thorup、Christina Schjøth-Eskesen、Pernille Thornild Møller、Ove Wiborg、Henrik Helligsø Jensen、Steffen Sinning、Birgit Schiøtt

  DOI：10.1124/mol.113.088922

  日期：2014.2

  dopamine transporter mutants with respect to a series of mazindol analogs has allowed us to determine the orientation of mazindol within the central binding site. We find that mazindol binds in the central substrate binding site, and that the transporter selectivity can be modulated through mutations of a few residues in the binding pocket. Mazindol is most likely to bind as the R-enantiomer. Tyrosines

  已经研究了Mazindol作为可卡因成瘾药物治疗的可能药物。四环化合物同时抑制多巴胺转运蛋白和5-羟色胺转运蛋白，简单的化学修饰大大改变了目标选择性。因此，对于了解5-羟色胺/多巴胺转运蛋白选择性的分子决定因素以及开发新的药物滥用疗法，Mazindol是一个有吸引力的支架。使用分子模型和合理选择的5-羟色胺和多巴胺转运蛋白突变体相对于一系列mazindol类似物的药理谱分析，使我们能够确定mazindol在中央结合位点内的方向。我们发现，mazindol在中央底物结合位点结合，转运蛋白的选择性可以通过结合口袋中一些残基的突变来调节。Mazindol最有可能作为R对映体结合。人5-羟色胺转运蛋白中的酪氨酸95和175以及人多巴胺转运蛋白中的相应的苯丙氨酸75和155是mazindol选择性的主要决定因素。发现与人类5-羟色胺转运蛋白Tyr175和多巴胺转运蛋白Phe155一起操纵7位取代基的
• METHODS AND COMPOSITIONS FOR TREATING CANCER
  申请人：Globavir BioSciences, Inc.

  公开号：US20160361298A1

  公开（公告）日：2016-12-15

  Described are compositions and methods for treating cancer. Some methods comprise the administration of an effective amount of at least one inhibitor of tryptophan 2,3-dioxygenase (TDO) and/or indoleamine 2,3-dioxygenase (IDO), optionally combined with one or more additional anti-cancer agents.
• US3935218A
  申请人：——

  公开号：US3935218A

  公开（公告）日：1976-01-27
• US3966955A
  申请人：——

  公开号：US3966955A

  公开（公告）日：1976-06-29