2-methyl-5-(1-piperazinyl)quinoline | 698981-81-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-methyl-5-(1-piperazinyl)quinoline
• 英文别名: 2-methyl-5-piperazin-1-yl-quinoline；5-piperazine-2-methylquinoline；2-Me-5-(1-piperazinyl)quinoline；2-methyl-5-piperazin-1-ylquinoline
• CAS: 698981-81-6
• 化学式: C₁₄H₁₇N₃
• 分子量: 227.309
• InChiKey: PZNAAXFCMFHGNR-UHFFFAOYSA-N

物化性质

• 沸点：
  405.8±35.0 °C(Predicted)
• 密度：
  1.128±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  28.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-methyl-5-(1-piperazinyl)quinoline 在 sodium methylate 、 三乙酰氧基硼氢化钠 作用下， 以 甲醇 、 二氯甲烷 、 formamide 为溶剂， 反应 1.33h， 生成 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4H-imidazo[5,1-c][1,4]benzoxazin-3-carboxamide
  参考文献：
  名称：

  Development of an Efficient Large-Scale Synthesis for a 4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide Derivative for Depression and Anxiety

  摘要：

  The development and scale-up of an optimized synthesis for a novel drug candidate for depression and anxiety is presented. The updated synthesis represents a convergent and efficient four-stage approach to the API, overcoming high cost of goods (COG), general lack of convergence, and low yield of previous routes. A lower cost of goods resulted from using 3-nitrosalicylaldehyde as a starting material and introducing the expensive side chain (2-methyl-5-(piperazin-1-yl)quinoline) at a later stage. Green chemistry principles were applied when a direct amidation enabled a straightforward conversion of the 4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxylate to the corresponding amide in the last step. In addition, the total number of stages was reduced from seven to four, and solvent usage was greatly minimized. The modified synthesis NUS demonstrated on a kilogram pilot scale, allowing the isolation of the API in 17% overall yield with the required purity.

  DOI：

  10.1021/op100103v
• 作为产物：
  描述：

  1,1-dimethylethyl 4-(2-methyl-5-quinolinyl)-1-piperazinecarboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以96%的产率得到2-methyl-5-(1-piperazinyl)quinoline
  参考文献：
  名称：

  发现1-（3- {2- [4-（2-甲基-5-喹啉基）-1-哌嗪基]乙基}苯基）-2-咪唑啉酮（GSK163090），这是一种有效的，选择性的和口服活性的5-HT 1A / B / D受体拮抗剂

  摘要：

  为了鉴定5-HT 1自身受体的选择性药物如泛拮抗剂，进行了研究以阐明先前报道的双重作用的5-HT 1拮抗剂/ SSRI结构。鉴定出一系列新颖的化合物，它们显示出较低的内在活性和对5-HT 1A，5-HT 1B和5-HT 1D受体的有效亲和力以及对5-羟色胺转运蛋白的高选择性。在这些化合物中，1-（3- {2- [4-（2-甲基-5-喹啉基）-1-哌嗪基]乙基}苯基）-2-咪唑啉酮（36）被发现具有强大的体内活性和强大的临床前可开发性，并且在此基础上将其选择为候选药物，目的是评估其作为快速发作的抗抑郁药/抗焦虑药的潜力。

  DOI：

  10.1021/jm100714c
• 作为试剂：
  描述：

  2-methyl-5-(1-piperazinyl)quinoline 、 ethyl 6-(2-oxoethyl)-4H-imidazo[5,1-c][1,4]benzoxazin-3-carboxylate 在 2-methyl-5-(1-piperazinyl)quinoline 作用下， 以29的产率得到ethyl 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4H-[5,1-c][1,4]benzoxazin-3-carboxylate
  参考文献：
  名称：

  Organic Process Research and Development 2010, 14, 859-867

  摘要：

  DOI：

文献信息

• [EN] FUSED TRICYCLIC DERIVATIVES FOR THE TREATMENT OF PSYCHOTIC DISORDERS<br/>[FR] DERIVES TRICYCLIQUES ACCOLES POUR LE TRAITEMENT DE TROUBLES PSYCHOTIQUES
  申请人：GLAXO GROUP LTD

  公开号：WO2006024517A1

  公开（公告）日：2006-03-09

  Compounds of formula (I) wherein R1, R2, X, A, Y, B, Z1, Q, p, r and s are defined in the specification for treating inter alia psychotic disorders, depressive disorders, anxiety disorders and sexual dysfunctions.

  式中R1、R2、X、A、Y、B、Z1、Q、p、r和s在说明书中定义的用于治疗精神疾病、抑郁障碍、焦虑障碍和性功能障碍的(I)式化合物。
• 5-{2-[4-(2-Methyl-5-quinolinyl)-1-piperazinyl]ethyl}-2(1H)-quinolinones and 3,4-dihydro-2(1H)-quinolinones: Dual-acting 5-HT1 receptor antagonists and serotonin reuptake inhibitors. Part 3
  作者：Steven M. Bromidge、Roberto Arban、Barbara Bertani、Manuela Borriello、Anna-Maria Capelli、Romano Di-Fabio、Stefania Faedo、Massimo Gianotti、Laurie J. Gordon、Enrica Granci、Alessandra Pasquarello、Simone K. Spada、Angela Worby、Laura Zonzini、Valeria Zucchelli

  DOI：10.1016/j.bmcl.2010.09.085

  日期：2010.12

  5-2-[4-(2-Methyl-5-quinolinyl)-1-piperazinyl]ethyl}-2(1H)-quinolinones and 3,4-dihydro-2(1H)-quinolinones have been identified with different combinations of 5-HT1 autoreceptor antagonist and hSerT potencies and excellent rat PK profiles. The availability of tool compounds with a range of profiles at targets known to play a key role in the control of synaptic 5-HT levels will allow exploration of

  5- 2- [4-（2-甲基-5-喹啉基）-1-哌嗪基]乙基} -2（1 H）-喹啉酮和3,4-二氢-2（1 H）-喹啉酮已被鉴定为5-HT 1自体受体拮抗剂和hSerT效力的不同组合以及出色的大鼠PK谱。在已知在控制突触5-HT水平中起关键作用的靶标上具有一系列分布图的工具化合物的可用性将允许在一系列动物行为和疾病模型中探索不同的药理分布图。
• [EN] QUINOLINE AND QUINAZOLINE DERIVATIVES HAVING AFFINITY FOR 5HT1-TYPE RECEPTORS<br/>[FR] DERIVES DE QUINOLINE ET DE QUINAZOLINE PRESENTANT UNE AFFINITE VIS-A-VIS DES RECEPTEURS DU TYPE 5HT1
  申请人：GLAXO GROUP LTD

  公开号：WO2005014552A1

  公开（公告）日：2005-02-17

  Compounds of formula (I) and pharmaceutically acceptable salts thereof are provided: wherein R1, m, X, R2, n, W, p, Y, Z, R3, R4, R5 and q have the meanings as defined in the description. Methods of preparation and uses thereof in therapy, particularly for CNS disorders such as depression or anxiety, are also disclosed.

  提供了式(I)的化合物及其药用盐：其中R1、m、X、R2、n、W、p、Y、Z、R3、R4、R5和q的含义如描述中所定义。还公开了制备方法以及在治疗中的用途，特别是用于抑郁症或焦虑等中枢神经系统疾病。
• Novel 5-HT1A/1B/1D receptors antagonists with potent 5-HT reuptake inhibitory activity
  作者：Halina T. Serafinowska、Frank E. Blaney、Peter J. Lovell、Giancarlo G. Merlo、Claire M. Scott、Paul W. Smith、Kathryn R. Starr、Jeannette M. Watson

  DOI：10.1016/j.bmcl.2008.08.110

  日期：2008.10

  5-HT(1A/1B/1D) receptors coupled with potent 5-HT reuptake inhibitory activity have been discovered. This is the first report describing docking of the lead compound 6-2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-2H-1,4-benzoxazin-3(4H)-one 1, into a model of the 5-HT transporter and the 5-HT(1A) receptor model.

  新型2-甲基-5-喹啉基-1-哌嗪基烷基-3,4-二氢-2H-1,4-苯并恶嗪-3-酮对5-HT（1A / 1B / 1D）受体表现出高亲和力，并与强效5偶联已经发现了-HT再摄取抑制活性。这是描述铅化合物6- 2- [4-（2-（5-甲基-5-喹啉基）-1-哌嗪基]乙基} -2H-1,4-苯并恶嗪-3（4H）-对接的第一份报告如图1所示，将模型转换成5-HT转运蛋白和5-HT（1A）受体模型。
• 6-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones: Dual-acting 5-HT1 receptor antagonists and serotonin reuptake inhibitors
  作者：Steven M. Bromidge、Barbara Bertani、Manuela Borriello、Stefania Faedo、Laurie J. Gordon、Enrica Granci、Matthew Hill、Howard R. Marshall、Luigi P. Stasi、Valeria Zucchelli、Giancarlo Merlo、Alessia Vesentini、Jeannette M. Watson、Laura Zonzini

  DOI：10.1016/j.bmcl.2008.08.084

  日期：2008.10

  Investigation of a series 6-[2-(4-aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones has led to the discovery of potent 5-HT(1A/1B/1D) receptor antagonists with and without additional SerT affinity. Modulation of the different target activities gave compounds with a range of profiles suitable for further in vivo characterization.

  对一系列6- [2-（2-（4-芳基-1-哌嗪基）乙基] -2H-1,4-苯并恶嗪-3（4H）-的研究导致了有效的5-HT（1A / 1B / 1D）具有和不具有其他SerT亲和力的受体拮抗剂。对不同靶标活性的调节使化合物具有适合进一步体内表征的一系列特征。