(3,4-difluorophenyl)(2-methylamino-3-pyridinyl)methanone | 1477730-39-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3,4-difluorophenyl)(2-methylamino-3-pyridinyl)methanone
• 英文别名: (3,4-Difluorophenyl)-[2-(methylamino)pyridin-3-yl]methanone；(3,4-difluorophenyl)-[2-(methylamino)pyridin-3-yl]methanone
• CAS: 1477730-39-4
• 化学式: C₁₃H₁₀F₂N₂O
• 分子量: 248.232
• InChiKey: LRRDNMQZEMSEID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3,4-difluorophenyl)(2-methylamino-3-pyridinyl)methanone 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以613 mg的产率得到(5-bromo-2-methylamino-3-pyridinyl)(3,4-difluorophenyl)methanone
  参考文献：
  名称：

  Design, Synthesis, and Activity of a Series of Arylpyrid-3-ylmethanones as Type I Positive Allosteric Modulators of α7 Nicotinic Acetylcholine Receptors

  摘要：

  A series of novel arylpyrid-3-ylmethanones (7a-aa) were designed as modulators of alpha 7 nicotinic acetylcholine receptors (nAChRs). The methanones were found to be type I positive allosteric modulators (PAMs) of human alpha 7 nAChRs expressed in Xenopus ooctyes. Structure-activity relationship (SAR) studies resulted in the identification of compound 7v as a potent and efficacious type I PAM with maximum modulation of a nicotine EC5 response of 1200% and EC50 = 0.18 mu M. Compound 7z was active in reversing the effect of scopolamine in the novel object recognition (NOR) paradigm with a minimum effective ip dose of 1.0 mg/kg (2.7 mu mol/kg). This effect was blocked by the selective alpha 7 nAChR antagonist methyllycaconitine (MLA). These compounds are nAChRs that may have therapeutic value in restoring impaired sensory Alzheimer's disease. potent type I positive allosteric modulators of alpha 7 gating and cognitive deficits in schizophrenia and Alzheimer's disease.

  DOI：

  10.1021/jm400704g
• 作为产物：
  描述：

  3,4-二氟苯甲醛 在 sodium acetate 、 pyridinium chlorochromate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 环己烷 为溶剂， 反应 5.5h， 生成 (3,4-difluorophenyl)(2-methylamino-3-pyridinyl)methanone
  参考文献：
  名称：

  Design, Synthesis, and Activity of a Series of Arylpyrid-3-ylmethanones as Type I Positive Allosteric Modulators of α7 Nicotinic Acetylcholine Receptors

  摘要：

  A series of novel arylpyrid-3-ylmethanones (7a-aa) were designed as modulators of alpha 7 nicotinic acetylcholine receptors (nAChRs). The methanones were found to be type I positive allosteric modulators (PAMs) of human alpha 7 nAChRs expressed in Xenopus ooctyes. Structure-activity relationship (SAR) studies resulted in the identification of compound 7v as a potent and efficacious type I PAM with maximum modulation of a nicotine EC5 response of 1200% and EC50 = 0.18 mu M. Compound 7z was active in reversing the effect of scopolamine in the novel object recognition (NOR) paradigm with a minimum effective ip dose of 1.0 mg/kg (2.7 mu mol/kg). This effect was blocked by the selective alpha 7 nAChR antagonist methyllycaconitine (MLA). These compounds are nAChRs that may have therapeutic value in restoring impaired sensory Alzheimer's disease. potent type I positive allosteric modulators of alpha 7 gating and cognitive deficits in schizophrenia and Alzheimer's disease.

  DOI：

  10.1021/jm400704g

文献信息

• Design, Synthesis, and Activity of a Series of Arylpyrid-3-ylmethanones as Type I Positive Allosteric Modulators of α7 Nicotinic Acetylcholine Receptors
  作者：Derk J. Hogenkamp、Thomas A. Ford-Hutchinson、Wen-Yen Li、Edward R. Whittemore、Ryan F. Yoshimura、Minhtam B. Tran、Timothy B. C. Johnstone、Gavin D. Bascom、Hannah Rollins、Lena Lu、Kelvin W. Gee

  DOI：10.1021/jm400704g

  日期：2013.11.14

  A series of novel arylpyrid-3-ylmethanones (7a-aa) were designed as modulators of alpha 7 nicotinic acetylcholine receptors (nAChRs). The methanones were found to be type I positive allosteric modulators (PAMs) of human alpha 7 nAChRs expressed in Xenopus ooctyes. Structure-activity relationship (SAR) studies resulted in the identification of compound 7v as a potent and efficacious type I PAM with maximum modulation of a nicotine EC5 response of 1200% and EC50 = 0.18 mu M. Compound 7z was active in reversing the effect of scopolamine in the novel object recognition (NOR) paradigm with a minimum effective ip dose of 1.0 mg/kg (2.7 mu mol/kg). This effect was blocked by the selective alpha 7 nAChR antagonist methyllycaconitine (MLA). These compounds are nAChRs that may have therapeutic value in restoring impaired sensory Alzheimer's disease. potent type I positive allosteric modulators of alpha 7 gating and cognitive deficits in schizophrenia and Alzheimer's disease.