3-(6-bromohexyl)benzo[d]oxazol-2(3H)-one | 1016539-20-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: 3-(6-bromohexyl)benzo[d]oxazol-2(3H)-one
• 英文别名: 3-(6-Bromohexyl)-1,3-benzoxazol-2-one
• CAS: 1016539-20-0
• 化学式: C₁₃H₁₆BrNO₂
• 分子量: 298.18
• InChiKey: UWHIPFXLKJBTNE-UHFFFAOYSA-N

物化性质

• 熔点：
  55 °C
• 沸点：
  385.0±44.0 °C(Predicted)
• 密度：
  1.393±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-环己基哌嗪 、 3-(6-bromohexyl)benzo[d]oxazol-2(3H)-one 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以76%的产率得到3-[6-(4-Cyclohexylpiperazin-1-yl)hexyl]-1,3-benzoxazol-2-one
  参考文献：
  名称：

  Conversion of a Highly Selective Sigma-1 Receptor–Ligand to Sigma-2 Receptor Preferring Ligands with Anticocaine Activity

  摘要：

  Cocaine's toxicity can be mitigated by blocking its interaction with sigma-1 receptors. The involvement of sigma-2 receptors remains unclear. To investigate their potential role, we have designed compounds through a convergent synthesis utilizing a highly selective sigma-1 ligand and elements of a selective sigma-2 ligand. Among the synthesized compounds was produced a subnanomolar sigma-2 ligand with an 11-fold preference over sigma-1 receptors. These compounds may be useful in developing effective pharmacotherapies for cocaine toxicity.

  DOI：

  10.1021/jm701357m
• 作为产物：
  描述：

  2-苯并唑啉酮 、 1,6-二溴己烷 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 4.0h， 生成 3-(6-bromohexyl)benzo[d]oxazol-2(3H)-one
  参考文献：
  名称：

  新型芳基哌嗪基烷基2-苯并恶唑酮和2-苯并噻唑酮作为5-HT 7和5-HT 1A受体配体的结构-活性关系和分子建模研究

  摘要：

  一种新型系列arylpiperazinylalkyl 2- benzoxazolones和2- benzothiazolones的18 - 38被设计，合成和测试，以评估其对5-HT亲和力7和5-HT 1A受体。具有2-苯并噻唑酮核的化合物通常具有比相应的2-苯并恶唑酮化合物更高的亲和力值。特别地，在2-苯并噻唑酮和芳基哌嗪之间具有六或七个碳链接头的衍生物的K i值在5-HT 1A受体的亚纳摩尔范围内，而在5-HT 7的纳摩尔范围低。受体，表明它们可能是有趣的双重配体。分子建模研究表明，在5-HT 1A和5-HT 7受体的同源性模型中，所研究化合物的对接姿势不同，这说明了它们在实验上确定的亲和力和普遍的低选择性。此外，结构相互作用指纹分析确定了两个5-羟色胺受体结合口袋内长链芳基哌嗪的特异性相互作用的重要氨基酸残基。

  DOI：

  10.1016/j.ejmech.2014.08.023

文献信息

• Structure–activity relationships and molecular modeling studies of novel arylpiperazinylalkyl 2-benzoxazolones and 2-benzothiazolones as 5-HT7 and 5-HT1A receptor ligands
  作者：Loredana Salerno、Valeria Pittalà、Maria N. Modica、Maria A. Siracusa、Sebastiano Intagliata、Alfredo Cagnotto、Mario Salmona、Rafał Kurczab、Andrzej J. Bojarski、Giuseppe Romeo

  DOI：10.1016/j.ejmech.2014.08.023

  日期：2014.10

  5-HT7 and 5-HT1A receptors. Compounds with a 2-benzothiazolone nucleus generally had affinity values higher than the corresponding 2-benzoxazolone compounds. In particular, derivatives possessing a six or seven carbon chain linker between 2-benzothiazolone and arylpiperazine had Ki values in the subnanomolar range for the 5-HT1A receptor and in the low nanomolar range for the 5-HT7 receptor, indicating

  一种新型系列arylpiperazinylalkyl 2- benzoxazolones和2- benzothiazolones的18 - 38被设计，合成和测试，以评估其对5-HT亲和力7和5-HT 1A受体。具有2-苯并噻唑酮核的化合物通常具有比相应的2-苯并恶唑酮化合物更高的亲和力值。特别地，在2-苯并噻唑酮和芳基哌嗪之间具有六或七个碳链接头的衍生物的K i值在5-HT 1A受体的亚纳摩尔范围内，而在5-HT 7的纳摩尔范围低。受体，表明它们可能是有趣的双重配体。分子建模研究表明，在5-HT 1A和5-HT 7受体的同源性模型中，所研究化合物的对接姿势不同，这说明了它们在实验上确定的亲和力和普遍的低选择性。此外，结构相互作用指纹分析确定了两个5-羟色胺受体结合口袋内长链芳基哌嗪的特异性相互作用的重要氨基酸残基。
• Design, synthesis and biological evaluation of bivalent benzoxazolone and benzothiazolone ligands as potential anti-inflammatory/analgesic agents
  作者：Ahmed H. Abdelazeem、Shabana I. Khan、Stephen W. White、Kenneth J. Sufka、Christopher R. McCurdy

  DOI：10.1016/j.bmc.2015.04.057

  日期：2015.7

  Benzoxazolone and benzothiazolone were used as template blocks to develop two series of dimers as anti-inflammatory and analgesic agents based on the concept of bivalent ligands. The first series (I) involved varying the carbon chain lengths extending from the piperazine core to the nitrogen atom of the dibenzo[d]oxazol-2(3H)-one or dibenzo[d]thiazol-2(3H)-one. The second series (II) was designed by changing the attachment point. All compounds were screened for their in vitro anti-inflammatory activity in terms of the inhibition of inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-kappa B). Seventeen compounds inhibited both targets. Eleven of them exhibited IC50 values below 3 mu M while five compounds showed IC50 values of 1 mu M or below. Most of the compounds were found to be devoid of cytotoxicity against mammalian kidney and solid tumors cell lines up to 25 mu g/mL. In vivo anti-inflammatory and antinociceptive studies revealed that compounds 3j, 5t and 8b have significant anti-inflammatory and analgesic activity comparable to that of indomethacin and ketorolac, respectively. (C) 2015 Elsevier Ltd. All rights reserved.
• Conversion of a Highly Selective Sigma-1 Receptor–Ligand to Sigma-2 Receptor Preferring Ligands with Anticocaine Activity
  作者：Christophe Mésangeau、Sanju Narayanan、Andrea M. Green、Jamaluddin Shaikh、Nidhi Kaushal、Eddy Viard、Yan-Tong Xu、James A. Fishback、Jacques H. Poupaert、Rae R. Matsumoto、Christopher R. McCurdy

  DOI：10.1021/jm701357m

  日期：2008.3.13

  Cocaine's toxicity can be mitigated by blocking its interaction with sigma-1 receptors. The involvement of sigma-2 receptors remains unclear. To investigate their potential role, we have designed compounds through a convergent synthesis utilizing a highly selective sigma-1 ligand and elements of a selective sigma-2 ligand. Among the synthesized compounds was produced a subnanomolar sigma-2 ligand with an 11-fold preference over sigma-1 receptors. These compounds may be useful in developing effective pharmacotherapies for cocaine toxicity.
• Chemical puzzles in the search for new, flexible derivatives of lurasidone as antipsychotic drugs
  作者：Przemysław Zaręba、Anna K. Drabczyk、Jolanta Jaśkowska、Grzegorz Satała

  DOI：10.1016/j.bmc.2020.115459

  日期：2020.5

  D2, 5-HT1A, 5-HT2A receptors are among the most important receptor targets in the treatment of schizophrenia, but antagonism at 5-HT6 and 5-HT7 receptors may bring about additional improvement of cognitive functions. However, doubt exists regarding the importance of 5-HT7R in the pharmacotherapy. In 2010, lurasidone (with high affinity for D2, D3, 5-HT1A, 5-HT2A, 5-HT7 receptors) was approved for the

  在精神分裂症的药物治疗中，缺乏有效的药物，并且当前使用的药物引起大量的副作用。D2、5-HT1A，5-HT2A受体是精神分裂症治疗中最重要的受体靶标，但对5-HT6和5-HT7受体的拮抗作用可能会进一步改善认知功能。然而，对于5-HT7R在药物治疗中的重要性存在疑问。2010年，批准了卢拉西酮（对D2，D3、5-HT1A，5-HT2A，5-HT7受体具有高亲和力）用于治疗精神分裂症。由于上述药物的功效以及与5-HT7R的作用有关的疑问，我们决定获得具有与lurasidone相似的活性谱，但对5-HT7R的亲和力降低而对5-HT6R的亲和力提高的化合物。以此目的，我们选择了卢拉西酮的柔性己基衍生物（2-（6-（4-（苯并[d]异噻唑-3-基）哌嗪-1-基）己基）六氢-1H-4,7-甲基异吲哚-1,3（2H ）-第1a）条是命中结构。经过分子建模，我们使用在其他已知的CNS药物中发现的部分在芳