77-LH-28-1 | 560085-11-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 77-LH-28-1
• 英文别名: 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one；1-[3-(4-butylpiperidin-1-yl)-propyl]-3,4-dihydro-1H-quinolin-2-one；1-[3-(4-butyl-1-piperidinyl)propyl]-3,4-dihydro-2(1H)-quinolinone；1-[3-(4-Butyl-piperidin-1-yl)-propyl]-3,4-dihydro-1H-quinolin-2-one；1-[3-(4-Butylpiperidin-1-yl)propyl]-3,4-dihydroquinolin-2-one
• CAS: 560085-11-2
• 化学式: C₂₁H₃₂N₂O
• 分子量: 328.498
• InChiKey: PHMGZAICAOYEAF-UHFFFAOYSA-N

物化性质

• 沸点：
  515.8±50.0 °C(Predicted)
• 密度：
  1.020±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  77-LH-28-1 、 草酸 以 丙酮 为溶剂， 生成 1-[3-(4-butylpiperidin-1-yl)-propyl]-3,4-dihydro-1H-quinolin-2-one oxalate
  参考文献：
  名称：

  Tetrahydroquinoline analogues as muscarinic agonists

  摘要：

  本发明涉及四氢喹啉化合物作为肌气镇剂受体激动剂；包含该化合物的组合物；使用该化合物抑制肌气镇剂受体活性的方法；使用该化合物治疗与肌气镇剂受体相关的疾病状况的方法；以及使用该化合物鉴定适合治疗的受试者的方法。

  公开号：

  US09522906B2
• 作为产物：
  描述：

  3,4-二氢-2(1H)-喹啉酮 在 sodium hydride 、 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 19.0h， 生成 77-LH-28-1
  参考文献：
  名称：

  Tetrahydroquinoline analogues as muscarinic agonists

  摘要：

  本发明涉及四氢喹啉化合物作为肌气镇剂受体激动剂；包含该化合物的组合物；使用该化合物抑制肌气镇剂受体活性的方法；使用该化合物治疗与肌气镇剂受体相关的疾病状况的方法；以及使用该化合物鉴定适合治疗的受试者的方法。

  公开号：

  US09522906B2

文献信息

• Muscarinic agonists
  申请人：Skjaerbaek Niels

  公开号：US20060199810A1

  公开（公告）日：2006-09-07

  The present invention relates to tetrahydroquinoline compounds as muscarinic receptor agonists; compositions comprising the same; methods of inhibiting an activity of a muscarinic receptor with said compounds; methods of treating a disease condition associated with a muscarinic receptor using said compounds; and methods for identifying a subject suitable for treatment using said compounds.

  本发明涉及四氢喹啉化合物作为毒蕈碱受体激动剂；包含该化合物的组合物；使用该化合物抑制毒蕈碱受体活性的方法；使用该化合物治疗与毒蕈碱受体相关的疾病条件的方法；以及使用该化合物识别适合使用该化合物治疗的受试者的方法。
• TETRAHYDROQUINOLINE ANALOGUES AS MUSCARINIC AGONISTS
  申请人：Skjaerback Niels

  公开号：US20090239903A1

  公开（公告）日：2009-09-24

  The present invention relates to tetrahydroquinoline compounds as muscarinic receptor agonists; compositions comprising the same; methods of inhibiting an activity of a muscarinic receptor with said compounds; methods of treating a disease condition associated with a muscarinic receptor using said compounds; and methods for identifying a subject suitable for treatment using said compounds.

  本发明涉及四氢喹啉化合物作为肌肉型乙酰胆碱受体激动剂；包含该化合物的组合物；使用该化合物抑制肌肉型乙酰胆碱受体活性的方法；使用该化合物治疗与肌肉型乙酰胆碱受体有关的疾病状态的方法；以及使用该化合物识别适合接受治疗的受试者的方法。
• Characterization of a CNS penetrant, selective M₁muscarinic receptor agonist, 77-LH-28-1
  作者：C J Langmead、N E Austin、C L Branch、J T Brown、K A Buchanan、C H Davies、I T Forbes、V A H Fry、J J Hagan、H J Herdon、G A Jones、R Jeggo、J N C Kew、A Mazzali、R Melarange、N Patel、J Pardoe、A D Randall、C Roberts、A Roopun、K R Starr、A Teriakidis、M D Wood、M Whittington、Z Wu、J Watson

  DOI：10.1038/bjp.2008.152

  日期：2008.7

  Background and purpose:M1muscarinic ACh receptors (mAChRs) represent an attractive drug target for the treatment of cognitive deficits associated with diseases such as Alzheimer's disease and schizophrenia. However, the discovery of subtype‐selective mAChR agonists has been hampered by the high degree of conservation of the orthosteric ACh‐binding site among mAChR subtypes. The advent of functional screening assays has enabled the identification of agonists such as AC‐42 (4‐n‐butyl‐1‐[4‐(2‐methylphenyl)‐4‐oxo‐1‐butyl]‐piperidine), which bind to an allosteric site and selectively activate the M1mAChR subtype. However, studies with this compound have been limited to recombinantly expressed mAChRs.Experimental approach:In this study, we have compared the pharmacological profile of AC‐42 and a close structural analogue, 77‐LH‐28‐1 (1‐[3‐(4‐butyl‐1‐piperidinyl)propyl]‐3,4‐dihydro‐2(1H)‐quinolinone) at human recombinant, and rat native, mAChRs by calcium mobilization, inositol phosphate accumulation and bothin vitroandin vivoelectrophysiology.Key results:Calcium mobilization and inositol phosphate accumulation assays revealed that both AC‐42 and 77‐LH‐28‐1 display high selectivity to activate the M1mAChR over other mAChR subtypes. Furthermore, 77‐LH‐28‐1, but not AC‐42, acted as an agonist at rat hippocampal M1receptors, as demonstrated by its ability to increase cell firing and initiate gamma frequency network oscillations. Finally, 77‐LH‐28‐1 stimulated cell firing in the rat hippocampusin vivofollowing subcutaneous administration.Conclusions and implications:These data suggest that 77‐LH‐28‐1 is a potent, selective, bioavailable and brain‐penetrant agonist at the M1mAChR and therefore that it represents a better tool than AC‐42, with which to study the pharmacology of the M1mAChR.British Journal of Pharmacology(2008)154, 1104–1115; doi:10.1038/bjp.2008.152; published online 5 May 2008
• IMPROVED DIFFERENTIATION METHOD
  申请人：Koninklijke Nederlandse Akademie van Wetenschappen

  公开号：EP3423565A1

  公开（公告）日：2019-01-09
• ENABLING METHODS TO IDENTIFY ALLOSTERIC MODULATORS OF RECEPTOR ACTIVITY
  申请人：Spalding Tracy A

  公开号：US20090209525A1

  公开（公告）日：2009-08-20

  A method developed to identify receptor modulators, involving providing a mutant receptor, wherein said mutant receptor has a mutation that alters the activity of said mutant receptor compared to a wild type receptor; contacting said mutant receptor with a candidate compound; and determining whether said candidate compound modulates the activity of said mutant receptor.