5-(4-bromophenyl)-2,3-dihydro-5-hydroxy-5H-imidazo<2,1-a>isoindole | 50800-56-1

• 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-(4-bromophenyl)-2,3-dihydro-5-hydroxy-5H-imidazo<2,1-a>isoindole
• 英文别名: 5-(4-bromo-phenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindol-5-ol；5-(4-bromophenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindol-5-ol；5-(4-Bromo-phenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindol-5-ol；5-(4-bromophenyl)-2,3-dihydroimidazo[1,2-b]isoindol-5-ol
• CAS: 50800-56-1
• 化学式: C₁₆H₁₃BrN₂O
• 分子量: 329.196
• InChiKey: RAZRHYOBZPAGEG-UHFFFAOYSA-N

物化性质

• 沸点：
  469.5±55.0 °C(Predicted)
• 密度：
  1.59±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  35.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(4-bromophenyl)-2,3-dihydro-5-hydroxy-5H-imidazo<2,1-a>isoindole 在 氮 、 乙酸乙酯 、 碳酸氢钠 、 Brine 、 Sodium sulfate-III 作用下， 以 溶剂黄146 为溶剂， 反应 6.5h， 生成 5-(4-bromophenyl)-5H-imidazo[2,1-a]isoindole
  参考文献：
  名称：

  Imidazoisoindole neuropeptide S receptor antagonists

  摘要：

  本发明涉及咪唑异异喹啉化合物，其为神经肽S受体拮抗剂，可用于治疗或预防神经系统和精神疾病，以及与神经肽S受体有关的疾病。本发明还涉及包含这些化合物的制药组合物以及这些化合物和组合物在预防或治疗神经肽S受体相关疾病中的使用。

  公开号：

  US08541595B2
• 作为产物：
  描述：

  2-苯基咪唑啉 、 对溴苯甲酸甲酯 在 正丁基锂 作用下， 生成 5-(4-bromophenyl)-2,3-dihydro-5-hydroxy-5H-imidazo<2,1-a>isoindole
  参考文献：
  名称：

  卤化的mazindol类似物可作为多巴胺转运蛋白上可卡因结合位点的潜在抑制剂。

  摘要：

  制备了一系列mazindol的卤代（F，Cl，Br，I），嘧啶基和二氮杂环庚烷同系物，并评估了它们在大鼠纹状体中取代[3H] WIN 35,428结合并抑制[3H]多巴胺（DA）吸收的能力。组织。除马嗪醇的2'-氯（6）和2'-溴（16）类似物外，所有化合物都比[R]-可卡因更能取代[3H] WIN 35,428的结合并更有效地抑制[3H] DA的吸收。结构活性研究表明，在咪唑系列中，使用在游离苯基的3'-或4'-位包含一个或两个Cl或Br原子的化合物，对[3H] WIN 35,428的结合产生了最佳抑制作用。用嘧啶环或二氮杂环庚烷环取代咪唑环可增强结合抑制作用。最有效的[3H] WIN 35,428结合和[3H] DA吸收抑制剂是6-（3'-氯苯基）-2,3,4，6-四氢嘧啶[2,1-α-异吲哚醇-6-醇（23; IC50 1.0 nM; 8 x mazindol）和7-（3'，4'-二氯苯基）-2

  DOI：

  10.1021/jm960288w

文献信息

• [EN] IMIDAZOISOINDOLE NEUROPEPTIDE S RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES IMIDAZOISOINDOLES DES RÉCEPTEURS DU NEUROPEPTIDE S
  申请人：MERCK SHARP & DOHME

  公开号：WO2010056567A1

  公开（公告）日：2010-05-20

  The present invention is directed to imidazoisoindole compounds which are antagonists of neuropeptide S receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which the neuropeptide S receptor is involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the neuropeptide S receptor is involved.

  本发明涉及嘌呤并异噁唑烷酮类化合物，这些化合物是神经肽S受体拮抗剂，可用于治疗或预防涉及神经肽S受体的神经和精神疾病。该发明还涉及含有这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及神经肽S受体的疾病中的用途。
• Imidazoisoindole Neuropeptide S Receptor Antagonists
  申请人：Manley Peter J.

  公开号：US20110212941A1

  公开（公告）日：2011-09-01

  The present invention is directed to imidazoisoindole compounds which are antagonists of neuropeptide S receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which the neuropeptide S receptor is involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the neuropeptide S receptor is involved.

  本发明涉及咪唑异异吲哚化合物，其为神经肽S受体的拮抗剂，并且在预防或治疗涉及神经肽S受体的神经和精神障碍和疾病方面是有用的。本发明还涉及包含这些化合物的制药组合物以及在预防或治疗涉及神经肽S受体的这种疾病方面使用这些化合物和组合物。
• Radiolabelling optimization of 5-(4-[125I]-iodophenyl)-2,3 dihydro-5-hydroxy-5H-imidazo[2,1-a]isoindole or [125I]-iodo mazindol : A potential tool for spect explorations
  作者：E. Galinier、J. E. Ombetta、Y. Frangin、J. Mertens、J. C. Besnard、D. Guilloteau

  DOI：10.1002/jlcr.2580340512

  日期：1994.5

  The radiolabelling of an iodinated analog of mazindol, 5-(4-[125I]-iodophenyl)-2,3-dihydro-5-hydroxy-5H-imidazo[2,1-a]isoindole, was performed in order to develop a potential tool for SPECT exploration of the presynaptic dopamine transporter in the human brain. Radiosynthesis was performed by iodide for bromide nucleophilic exchange from a brominated precursor. The reaction was carried out in the presence

  对马吲哚的碘化类似物 5-(4-[125I]-iodophenyl)-2,3-dihydro-5-hydroxy-5H-imidazo[2,1-a]isoindole 进行放射性标记，以开发SPECT 探索人脑中突触前多巴胺转运蛋白的潜在工具。放射性合成是通过碘化物进行的，用于溴化前体的溴化物亲核交换。该反应在铜Ⅰ催化剂以及还原剂和络合剂的存在下进行。在这些放射性标记条件下，[125I] iodomazindol 表现出互变异构平衡。因此，为了获得最佳标记条件，我们研究了反应中涉及的诸如铜 I 催化剂和溴化前体浓度、反应温度和加热时间等变量。这种动力学研究可以用作其他化合物的放射合成模式，这些化合物在特定条件下可以以互变异构平衡存在。事实上，我们描述了在最佳放射性标记条件下获得具有高放射化学纯度的每种互变异构形式的便捷程序。
• Tricyclic imidazole antagonists of the Neuropeptide S Receptor
  作者：B. Wesley Trotter、Kausik K. Nanda、Peter J. Manley、Victor N. Uebele、Cindra L. Condra、Anthony L. Gotter、Karsten Menzel、Martin Henault、Rino Stocco、John J. Renger、George D. Hartman、Mark T. Bilodeau

  DOI：10.1016/j.bmcl.2010.04.016

  日期：2010.8

  A new structural class of potent antagonists of the Neuropeptide S Receptor (NPSR) is reported. High-throughput screening identified a tricyclic imidazole antagonist of NPSR, and medicinal chemistry optimization of this structure was undertaken to improve potency against the receptor as well as CNS penetration. Detailed herein are synthetic and medicinal chemistry studies that led to the identification of antagonists 15 and NPSR-PI1, which demonstrate potent in vitro NPSR antagonism and central exposure in vivo. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis of halogenated analogs of 5-(4-chlorophenyl)-2,3-dihydro-5-hydroxy-5H-imidazo[2,1-a]-isoindole or mazindol for exploration of the dopamine transporter
  作者：E Galinier、L Garreau、AM Dognon、JE Ombetta-Goka、Y Frangin、S Chalon、JC Besnard、D Guilloteau

  DOI：10.1016/0223-5234(93)90047-i

  日期：1993.1

  In order to study the presynaptic dopamine transporter in the human brain by single photon emission tomography (SPET) or positron emission tomography (PET) we have developed new halogenated mazindol derivatives using a pathway involving a reaction between a dilithio derivative of 2-phenyl-2-imidazoline and appropriate methyl or ethyl halogenobenzoates. After HPLC purification and chemical characterization, the affinity for the dopamine transporter was studied in vitro with [H-3]-GBR 12935 and compared to mazindol and nomifensine. Affinity potencies were determined as follow:- mazindol > brominated derivatives > iodinated derivatives > nomifensine > fluorinated derivatives. The properties were related tot eh structure of these compounds and showed the importance of the nature of the substituent on the primary phenyl ring of mazindol for affinity to the dopamine transporter.