4-(3-(4-aminopiperidin-1-yl)propyl)-2H-benzo[b][1,4]oxazin-3(4H)-one | 1186230-36-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 4-(3-(4-aminopiperidin-1-yl)propyl)-2H-benzo[b][1,4]oxazin-3(4H)-one
• 英文别名: 4-[3-(4-aminopiperidin-1-yl)propyl]-4H-benzo[1,4]oxazin-3-one；4-[3-(4-amino-piperidin-1-yl)-propyl]-4H-benzo[1,4]oxazin-3-one；4-[3-(4-Aminopiperidin-1-yl)propyl]-1,4-benzoxazin-3-one
• CAS: 1186230-36-3
• 化学式: C₁₆H₂₃N₃O₂
• 分子量: 289.378
• InChiKey: WLKDZVMRFQBGBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  58.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(3-(4-aminopiperidin-1-yl)propyl)-2H-benzo[b][1,4]oxazin-3(4H)-one 、 苯乙酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以64%的产率得到Lu AE51090
  参考文献：
  名称：

  [EN] NOVEL HETEROCYCLIC CARBOXAMIDES AS M1 AGONISTS
  [FR] NOUVEAUX CARBOXAMIDES HÉTÉROCYCLIQUES COMME AGONISTES DE M1

  摘要：

  本发明涉及式(I)的新型M1激动化合物及其在治疗与精神分裂症等疾病相关的认知障碍以及在治疗其他通过胆碱能M1受体介导的疾病中的应用。

  公开号：

  WO2009106534A1
• 作为产物：
  描述：

  4-(3-bromopropyl)-2H-benzo[b][1,4]oxazin-3(4H)-one 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 4-(3-(4-aminopiperidin-1-yl)propyl)-2H-benzo[b][1,4]oxazin-3(4H)-one
  参考文献：
  名称：

  Proof of Concept Study for Designed Multiple Ligands Targeting the Dopamine D₂, Serotonin 5-HT_2A, and Muscarinic M₁ Acetylcholine Receptors

  摘要：

  Herein we describe the hybridization of a benzoxazinone M-1 scaffold with D-2 privileged structures derived from putative and clinically relevant antipsychotics to develop designed multiple ligands. The M-1 mAChR is an attractive target for the cognitive deficits in key CNS disorders. Moreover, activity at D-2 and 5-HT2A receptors has proven useful for antipsychotic efficacy. We identified 9 which retained functional activity at the target M-1 mAChR and D2R and demonstrated high affinity for the 5-HT2AR.

  DOI：

  10.1021/jm5013243

文献信息

• Discovery of <i>N</i>-{1-[3-(3-Oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): An Allosteric Muscarinic M₁ Receptor Agonist with Unprecedented Selectivity and Procognitive Potential
  作者：Anette G. Sams、Morten Hentzer、Gitte K. Mikkelsen、Krestian Larsen、Christoffer Bundgaard、Niels Plath、Claus T. Christoffersen、Benny Bang-Andersen

  DOI：10.1021/jm100697g

  日期：2010.9.9

  The discovery and structure activity relationship (SAR) of a series of allosteric muscarinic M, receptor agonists are described. Compound 17 (Lu AE51090) was identified as a representative compound from the series, based on its high selectivity as an agonist at the muscarinic M-1 receptor across a panel of muscarinic receptor subtypes. Furthermore, 17 displayed a high degree of selectivity when tested in a broad panel of G-protein-coupled receptors, ion channels, transporters, and enzymes, and 17 showed an acceptable pharmacokinetic profile and sufficient brain exposure in rodents in order to characterize the compound in vivo. Hence, in a rodent model of learning and memory, 17 reversed delay-induced natural forgetting, suggesting a procognitive potential of 17.