3-(4-(dimethylamino)phenyl)-1-(pyridin-2-yl)propan-1-one | 1327143-07-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-(4-(dimethylamino)phenyl)-1-(pyridin-2-yl)propan-1-one
• 英文别名: 3-[4-(Dimethylamino)phenyl]-1-pyridin-2-ylpropan-1-one；3-[4-(dimethylamino)phenyl]-1-pyridin-2-ylpropan-1-one
• CAS: 1327143-07-6
• 化学式: C₁₆H₁₈N₂O
• 分子量: 254.332
• InChiKey: SSRPHKROFVPXHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (E)-3-(4-(dimethylamino)phenyl)-1-(pyridin-2-yl)prop-2-en-1-one 在 二苯硫醚 、 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以51%的产率得到3-(4-(dimethylamino)phenyl)-1-(pyridin-2-yl)propan-1-one
  参考文献：
  名称：

  Tuning Reactivity of Diphenylpropynone Derivatives with Metal-Associated Amyloid-β Species via Structural Modifications

  摘要：

  A diphenylpropynone derivative, DPP2, has been recently demonstrated to target metal-associated amyloid-beta (metal-A beta) species implicated in Alzheimer's disease (AD). DPP2 was shown to interact with metal-A beta species and subsequently control A beta aggregation (reactivity) in vitro; however, its cytotoxicity has limited further biological applications. In order to improve reactivity toward A beta species and lower cytotoxicity, along with gaining an understanding of a structure-reactivity-cytotoxicity relationship, we designed, prepared, and characterized a series of small molecules (C1/C2, P1/P2, and PA1/PA2) as structurally modified DPP2 analogues. A similar metal binding site to that of DPP2 was contained in these compounds while their structures were varied to afford different interactions and reactivities with metal ions, A beta species, and metal-A beta species. Distinct reactivities of our chemical family toward in vitro A beta aggregation in the absence and presence of metal ions were observed. Among our chemical series, the compound (C2) with a relatively rigid backbone and a dimethylamino group was observed to noticeably regulate both metal-free and metal-mediated A beta aggregation to different extents. Using our compounds, cell viability was significantly improved, compared to that with DPP2. Lastly, modifications on the DPP framework maintained the structural properties for potential blood-brain barrier (BBB) permeability. Overall, our studies demonstrated that structural variations adjacent to the metal binding site of DPP2 could govern different metal binding properties, interactions with A beta and metal-A beta species, reactivity toward metal-free and metal-induced A beta aggregation, and cytotoxicity of the compounds, establishing a structure-reactivity-cytotoxicity relationship. This information could help gain insight into structural optimization for developing nontoxic chemical reagents toward targeting metal-A beta species and modulating their reactivity in biological systems.

  DOI：

  10.1021/ic400851w

文献信息

• Tuning Reactivity of Diphenylpropynone Derivatives with Metal-Associated Amyloid-β Species via Structural Modifications
  作者：Yuzhong Liu、Akiko Kochi、Amit S. Pithadia、Sanghyun Lee、Younwoo Nam、Michael W. Beck、Xiaoming He、Dongkuk Lee、Mi Hee Lim

  DOI：10.1021/ic400851w

  日期：2013.7.15

  A diphenylpropynone derivative, DPP2, has been recently demonstrated to target metal-associated amyloid-beta (metal-A beta) species implicated in Alzheimer's disease (AD). DPP2 was shown to interact with metal-A beta species and subsequently control A beta aggregation (reactivity) in vitro; however, its cytotoxicity has limited further biological applications. In order to improve reactivity toward A beta species and lower cytotoxicity, along with gaining an understanding of a structure-reactivity-cytotoxicity relationship, we designed, prepared, and characterized a series of small molecules (C1/C2, P1/P2, and PA1/PA2) as structurally modified DPP2 analogues. A similar metal binding site to that of DPP2 was contained in these compounds while their structures were varied to afford different interactions and reactivities with metal ions, A beta species, and metal-A beta species. Distinct reactivities of our chemical family toward in vitro A beta aggregation in the absence and presence of metal ions were observed. Among our chemical series, the compound (C2) with a relatively rigid backbone and a dimethylamino group was observed to noticeably regulate both metal-free and metal-mediated A beta aggregation to different extents. Using our compounds, cell viability was significantly improved, compared to that with DPP2. Lastly, modifications on the DPP framework maintained the structural properties for potential blood-brain barrier (BBB) permeability. Overall, our studies demonstrated that structural variations adjacent to the metal binding site of DPP2 could govern different metal binding properties, interactions with A beta and metal-A beta species, reactivity toward metal-free and metal-induced A beta aggregation, and cytotoxicity of the compounds, establishing a structure-reactivity-cytotoxicity relationship. This information could help gain insight into structural optimization for developing nontoxic chemical reagents toward targeting metal-A beta species and modulating their reactivity in biological systems.