1-chloropropyl-4-pyrimidin-2-yl-piperazine | 99012-90-5

• 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: 1-chloropropyl-4-pyrimidin-2-yl-piperazine
• 英文别名: 1-(3-chlorophenyl)-4-(2-pyrimidinyl)piperazine；1-(3-chloropropyl)-4-(2-pyrimidinyl)piperazine；2-(4-(3-chloropropyl)piperazin-1-yl)pyrimidine；1-(3-chloropropyl)-4-(2-pyrimidyl)piperazine；3-[4-(2-Pyrimidinyl)piperazinyl]propyl chloride；2-[4-(3-chloropropyl)piperazin-1-yl]pyrimidine
• CAS: 99012-90-5
• 化学式: C₁₁H₁₇ClN₄
• 分子量: 240.736
• InChiKey: SIAOZTGWWPNJOD-UHFFFAOYSA-N

物化性质

• 熔点：
  59-61 °C
• 沸点：
  392.9±52.0 °C(Predicted)
• 密度：
  1.176±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  32.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-chloropropyl-4-pyrimidin-2-yl-piperazine 在 copper(l) iodide 、 sodium azide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 11-((1-(3-(4-pyrimidin-2-ylpiperazin-1-yl)propyl)-1H-1,2,3-triazol-4-yl)methoxy)-N-propylnoraporphine
  参考文献：
  名称：

  Further SAR study on 11-O-substituted aporphine analogues: Identification of highly potent dopamine D3 receptor ligands

  摘要：

  A series of new aporphine analogues (aporlogues) were prepared from appropriate aporphine precursors and arylpiperazines using the Click reaction protocol. These compounds displayed good to high affinity at the D-3 receptor, low or no affinity at the D-1 and D-2 receptors. Compounds 7f and 11c stood out as the most potent at the D-3 receptor among our newly synthesized aporlogues with K-i values of 2.67 and 1.14 nM, respectively. Further assay at the 5-HT1A receptor revealed that aporlogues 7f and 11c also showed high affinity at this receptor with K-i values of 9.68 and 7.59 nM, respectively. They were 3.6- and 6.6-fold more potent at the D-3 over 5-HT1A receptors. Such D-3/5-HT1A dual property of these compounds may be useful in the treatment of several brain disorders. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.053
• 作为产物：
  描述：

  1-(2-嘧啶基)哌嗪 、 1-溴-3-氯丙烷 在 sodium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 生成 1-chloropropyl-4-pyrimidin-2-yl-piperazine
  参考文献：
  名称：

  多巴胺D 3受体配体的新苯并内酰胺衍生物的合成，结合亲和性和SAR

  摘要：

  合成了一系列新的苯并内酰胺衍生物，并评估了它们在多巴胺D 1，D 2和D 3受体上的亲和力。这些化合物中的一些显示出比D 1受体更高的D 2和/或D 3亲和力和选择性。这些化合物的SAR研究揭示了决定性地影响其D 2和D 3亲和力的结构特征。该系列一些最具代表性的化合物与D 2和D 3之间的配合物的结构模型获得受体的目的是使观察到的实验结果合理化。此外，选定的化合物对5-HT 2A表现出中等的结合亲和力，这可能有助于减少作为潜在抗精神病药的锥体束外副作用的发生。

  DOI：

  10.1016/j.bmcl.2009.01.067

文献信息

• N-(substituted piperazinyl) alkylbicyclic succinimide derivatives
  申请人：Sumitomo Chemical Company, Limited

  公开号：US04598078A1

  公开（公告）日：1986-07-01

  A succinimide derivative of the formula: ##STR1## wherein A is straight or branched C.sub.2 -C.sub.6 alkylene or alkenylene, B is straight or branched C.sub.3 -C.sub.5 alkylene, D is straight or branched C.sub.2 -C.sub.3 alkylene, E is straight or branched C.sub.2 -C.sub.3 alkylene, R.sup.1 and R.sup.2 are each hydrogen or C.sub.1 -C.sub.4 alkyl, or they may form a single bond and R.sup.3 is a phenyl group optionally substituted with C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halogen and/or trifluoromethyl, a 2-pyridyl group optionally substituted with halogen, a 2-pyrimidyl group optionally substituted with halogen, a group of the formula: ##STR2## (in which R.sup.4 is hydrogen or phenyl), a group of the formula: CO--R.sup.5 (in which R.sup.5 is adamantyl or furyl) or hydroxy (C.sub.2 -C.sub.4) alkyl, and an acid addition salt thereof, which are useful as anti-anxiety drugs and/or anti-allergic drugs.

  一种琥珀酰亚胺衍生物的化学式：##STR1## 其中A是直链或支链的C.sub.2 -C.sub.6烷基或烯基，B是直链或支链的C.sub.3 -C.sub.5烷基，D是直链或支链的C.sub.2 -C.sub.3烷基，E是直链或支链的C.sub.2 -C.sub.3烷基，R.sup.1和R.sup.2分别是氢或C.sub.1 -C.sub.4烷基，或它们可以形成单键，R.sup.3是苯基，可选择地取代为C.sub.1 -C.sub.4烷基，C.sub.1 -C.sub.4烷氧基，卤素和/或三氟甲基，一个可选择地取代为卤素的2-吡啶基，一个可选择地取代为卤素的2-嘧啶基，一个化学式的基团：##STR2##（其中R.sup.4是氢或苯基），一个化学式的基团：CO--R.sup.5（其中R.sup.5是金刚烷基或呋喃基）或羟基（C.sub.2 -C.sub.4）烷基，以及其酸盐加合物，可用作抗焦虑药物和/或抗过敏药物。
• Design, synthesis, and biological evaluation of arylpiperazine–benzylpiperidines with dual serotonin and norepinephrine reuptake inhibitory activities
  作者：Suresh Paudel、Srijan Acharya、Kyeong-Man Kim、Seung Hoon Cheon

  DOI：10.1016/j.bmc.2016.03.044

  日期：2016.5

  The limitations of established serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) reuptake inhibitors necessitate the development of safer and more effective therapeutic agents. Based on the structures of 4-benzylpiperidine carboxamides and trazodone, arylpiperazine–benzylpiperidines with chemical scaffolds different from those of marketed drugs were designed, synthesized, and evaluated

  既定的5-羟色胺（5-羟色胺，5-HT）和去甲肾上腺素（NE）再摄取抑制剂的局限性需要开发更安全，更有效的治疗剂。根据4-苄基哌啶羧酰胺和曲唑酮的结构，设计，合成和评估化学支架与市售药物不同的芳基哌嗪-苄基哌啶，并评估其对神经递质再摄取的抑制活性。大多数合成化合物显示出比5-HT再摄取抑制更大的NE。其活性甚至大于标准药物盐酸文拉法辛。具有三碳连接基的衍生物表现出比具有二碳连接基的衍生物更好的活性。在新合成的化合物中，第2d表现出最强的神经递质再摄取抑制作用（ NE的IC 50 = 0.38μM，5-HT的IC 50 = 1.18μM）。生物学活性数据表明，芳基哌嗪-苄基哌啶具有开发作为治疗神经精神病和神经退行性疾病的新型治疗剂的潜力。
• Synthesis, 3D-QSAR, and Structural Modeling of Benzolactam Derivatives with Binding Affinity for the D2 and D3 Receptors
  作者：Laura López、Jana Selent、Raquel Ortega、Christian F. Masaguer、Eduardo Domínguez、Filipe Areias、José Brea、María Isabel Loza、Ferran Sanz、Manuel Pastor

  DOI：10.1002/cmdc.201000101

  日期：——

  series of 37 benzolactam derivatives were synthesized, and their respective affinities for the dopamine D2 and D3 receptors evaluated. The relationships between structures and binding affinities were investigated using both ligand‐based (3D‐QSAR) and receptor‐based methods. The results revealed the importance of diverse structural features in explaining the differences in the observed affinities, such as

  合成了一系列37种苯并内酰胺衍生物，并评估了它们各自对多巴胺D 2和D 3受体的亲和力。使用基于配体的方法（3D-QSAR）和基于受体的方法研究了结构与结合亲和力之间的关系。结果表明，在解释所观察到的亲和力方面的差异（例如苯并内酰胺羰基氧的位置或化合物的总长度）时，各种结构特征的重要性。对于D 2和D 3，此类配体性质的最佳值略有不同即使结合位点表现出非常高的同源性，受体也是如此。我们解释通过氢键网络的在d中存在这些差异2受体这是在d缺席3受体并限制了结合口袋的尺寸，造成在螺旋7个残基变得不那么访问。这些结果对设计更有效和选择性更高的苯并内酰胺衍生物的意义进行了介绍和讨论。
• Synthesis of New S-alkylated-3-mercapto-1,2,4-triazole Derivatives Bearing Cyclic Amine Moiety as Potent Anticancer Agents
  作者：M. S.R. Murty、Kesur R. Ram、Rayudu Venkateswara Rao、J. S. Yadav、Janapala Venkateswara Rao、L. R. Velatooru

  DOI：10.2174/157018012799129882

  日期：2012.3.1

  A series of 3-[3-[4-(Substituted)-1-cyclicamine]propyl]thio-5-substituted[1,2,4]triazoles (8a-j) were synthesized with good yields starting from corresponding carboxylic acids. The cytotoxicity studies of these derivatives were studied against five different human cancer cell lines. Three compounds had shown good anticancer activity. The triazole derivatives, 8i and 8j were most potent particularly against U937 and HL-60 cells. The cytotoxic potency of the compounds varied between the cell lines suggesting that a structural property of these compounds as possible determinants of their biological activity.

  一系列3-[3-[4-(取代)-1-环胺]丙基]硫-5-取代[1,2,4]三唑(8a-j)，从相应的羧酸出发，以良好的收率被合成。这些衍生物对五种不同的人类癌细胞系进行了细胞毒性研究。三种化合物显示出良好的抗癌活性。三唑衍生物，8i和8j，对U937和HL-60细胞尤其有效。化合物的细胞毒性效力在不同细胞系之间有所变化，这表明这些化合物的结构特性可能是其生物活性的可能决定因素。
• Synthesis of New Arylpiperazinylalkylthiobenzimidazole, Benzothiazole, or Benzoxazole Derivatives as Potent and Selective 5-HT_1A Serotonin Receptor Ligands
  作者：Maria A. Siracusa、Loredana Salerno、Maria N. Modica、Valeria Pittalà、Giuseppe Romeo、Maria E. Amato、Mateusz Nowak、Andrzej J. Bojarski、Ilario Mereghetti、Alfredo Cagnotto、Tiziana Mennini

  DOI：10.1021/jm800176x

  日期：2008.8.1

  A series of new compounds containing a benzimidazole, benzothiazole, or benzoxazole nucleus linked to an arylpiperazine by different thioalkyl chains was prepared. They were tested in radioligand binding experiments to evaluate their affinity for 5-HT 1A and 5-HT 2A serotonergic, alpha 1 adrenergic, D1, and D2 dopaminergic receptors. Many of tested compounds showed an interesting binding profile; in

  制备了一系列新化合物，其中包含通过不同的硫代烷基链与芳基哌嗪连接的苯并咪唑，苯并噻唑或苯并恶唑核。在放射性配体结合实验中对它们进行了测试，以评估它们对5-HT 1A和5-HT 2A血清素能，α1肾上腺素能，D1和D2多巴胺能受体的亲和力。许多测试化合物显示出有趣的结合特性；特别是，有36种化合物对5-HT 1A受体的亲和力和选择性高于所有其他研究受体。在功能测定中评估的选定化合物对5-HT 1A受体显示拮抗或部分激动活性。使用NMR和建模技术进行的广泛构象研究表明，在真空中，溶液中以及与5-HT 1A受体相互作用期间，扩展的构象占优势。最后，