N-(piperidine-4-yl-methyl)-2,3-dihydro-1,4-benzodioxine-5-carboxamide | 261767-15-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: N-(piperidine-4-yl-methyl)-2,3-dihydro-1,4-benzodioxine-5-carboxamide
• 英文别名: N-(4-piperidinyl)methyl-2,3-dihydro-1,4-benzodioxine-5-carboxamide；2,3-Dihydrobenzo[1,4]dioxine-5-carboxylic acid(piperidin-4-ylmethyl)amide；N-(piperidin-4-ylmethyl)-2,3-dihydro-1,4-benzodioxine-5-carboxamide
• CAS: 261767-15-1
• 化学式: C₁₅H₂₀N₂O₃
• 分子量: 276.335
• InChiKey: GPCGWBDMPPASTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  59.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(piperidine-4-yl-methyl)-2,3-dihydro-1,4-benzodioxine-5-carboxamide 在 TEA 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-[[1-[3-(4-propan-2-ylsulfonylpiperazin-1-yl)sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide
  参考文献：
  名称：

  Identification of a 5-HT4 receptor antagonist clinical candidate through side-chain modification

  摘要：

  Replacement of the N-butyl side-chain of lead 5-HT4 receptor antagonist 2 with propanesulfonylpiperidinyl, morpholinyl, and piperazinyl groups led to higher affinity analogs 4-6. In vitro drug metabolism screens and cassette pharmacokinetic studies in the dog led to identification of the N-methylpiperazinyl analog (6b), which displayed pharmacokinetic, selectivity, and safety parameters sufficient for advancement to the clinic for the treatment of urinary incontinence. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.039
• 作为产物：
  描述：

  2,3-二氢-1,4-苯并二恶烷-5-羰酰氯 在 TEA 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-(piperidine-4-yl-methyl)-2,3-dihydro-1,4-benzodioxine-5-carboxamide
  参考文献：
  名称：

  Identification of a 5-HT4 receptor antagonist clinical candidate through side-chain modification

  摘要：

  Replacement of the N-butyl side-chain of lead 5-HT4 receptor antagonist 2 with propanesulfonylpiperidinyl, morpholinyl, and piperazinyl groups led to higher affinity analogs 4-6. In vitro drug metabolism screens and cassette pharmacokinetic studies in the dog led to identification of the N-methylpiperazinyl analog (6b), which displayed pharmacokinetic, selectivity, and safety parameters sufficient for advancement to the clinic for the treatment of urinary incontinence. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.039

文献信息

• Discovery and pharmacological profile of new hydrophilic 5-HT 4 receptor antagonists
  作者：Bjarne Brudeli、Mirusha Navaratnarajah、Kjetil Wessel Andressen、Ornella Manfra、Lise Román Moltzau、Nils Olav Nilsen、Finn Olav Levy、Jo Klaveness

  DOI：10.1016/j.bmcl.2014.06.083

  日期：2014.9

  The synthesis and pharmacological data of some new and potent hydrophilic 5-HT4 receptor antagonists are described. Propanediol derivative 25 was identified as a potent antagonist with low affinity for the hERG potassium channel and promising pharmacokinetics.

  描述了一些新的和有效的亲水性5-HT 4受体拮抗剂的合成和药理学数据。丙二醇衍生物25被确定为对hERG钾通道的低亲和力和有希望的药代动力学的强效拮抗剂。
• 由2-重氮-1,3-二羰基化合物作为酰化试剂制 备酰胺化合物的方法
  申请人：山西师范大学

  公开号：CN106554290B

  公开（公告）日：2018-09-25

  本发明提供一种由2‑重氮‑1,3‑二羰基化合物作为酰化试剂在非金属催化、中性条件下制备酰胺化合物的方法。该方法以2‑重氮‑1,3‑二羰基化合物为原料，对不同的氨基化合物进行不同的苯甲酰基保护，从而制备一些列酰胺化合物。该方法在中性条件下进行，避免了传统的碱性条件对反应底物的局限性。反应条件温和，反应效率高、操作简单，为一些酰胺类化合物的制备以及氨基的保护提供了一种全新的、更便捷的方法，可应用于化学医药、生物、材料等领域。
• 5-HTX MODULATORS
  申请人：Klaveness Jo

  公开号：US20090029979A1

  公开（公告）日：2009-01-29

  This invention relates to compounds which bind to serotonin receptors inside or outside the central nervous system, in particular compounds which bind to the 5-HT 2 or 5-HT 7 receptors, their preparation and use, compositions containing them, and methods of treatment using them.

  本发明涉及与中枢神经系统内或外的血清素受体结合的化合物，特别是与5-HT2或5-HT7受体结合的化合物，其制备和使用，包含它们的组合物以及使用它们的治疗方法。
• Modulators of Preripheral 5-Ht Receptors
  申请人：Klaveness Jo

  公开号：US20070254874A1

  公开（公告）日：2007-11-01

  Novel modulators of 5-HT4 receptors have been developed which have a selectivity for peripheral receptors rather than those of the central nervous systems. Theses include novel derivatives of known modulators as well as entirely novel entities. Surprisingly, the derivatised compounds of the known modulators maintain a high binding affinity to 5-HT4 receptors, despite the presence of an acidic moiety at the end of an optional chain. The entirely novel entities also exhibit good binding affinity to 5-HT4 receptors. All of the compounds of the invention have a common motif which includes a basic nitrogen moiety and an acidic moiety. The compounds of the invention, due at least in part to their high ionisation potential at physiological pH, have the unique properties of selectively for peripheral 5HT4 receptors over those of the CNS, good binding affinity, and selectively of 5HT4 receptors over other serotonin receptors.

  已经开发出了5-HT4受体的新型调节剂，其选择性针对的是外周受体而非中枢神经系统受体。其中包括已知调节剂的新型衍生物以及全新的实体。令人惊讶的是，已知调节剂的衍生物化合物尽管在可选链的末端存在酸性基团，但仍保持对5-HT4受体的高结合亲和力。全新的实体也表现出良好的5-HT4受体结合亲和力。发明中的所有化合物都具有一个共同的基团，其中包括一种碱性氮基团和一种酸性基团。该发明中的化合物，至少部分原因是由于它们在生理pH值下具有高离化电位，具有选择性地作用于外周5-HT4受体而非中枢神经系统受体，具有良好的结合亲和力，并且对5-HT4受体的选择性高于其他血清素受体。
• US06172062B2
  申请人：——

  公开号：——

  公开（公告）日：——