(3-allyloxy-5-bromo-phenyl)methanol | 1367877-78-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (3-allyloxy-5-bromo-phenyl)methanol
• 英文别名: (3-Bromo-5-prop-2-enoxyphenyl)methanol；(3-bromo-5-prop-2-enoxyphenyl)methanol
• CAS: 1367877-78-8
• 化学式: C₁₀H₁₁BrO₂
• 分子量: 243.1
• InChiKey: KINIMEPAYZGJBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3-allyloxy-5-bromo-phenyl)methanol 在 吗啉 、 四(三苯基膦)钯 、 potassium carbonate 、 甲基磺酰氯 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 45.0h， 生成
  参考文献：
  名称：

  Discovery of Cyclic Sulfone Hydroxyethylamines as Potent and Selective β-Site APP-Cleaving Enzyme 1 (BACE1) Inhibitors: Structure-Based Design and in Vivo Reduction of Amyloid β-Peptides

  摘要：

  Structure-based design of a series of cyclic hydroxyethylamine BACE1 inhibitors allowed the rational incorporation of prime- and nonprime-side fragments to a central core template without any amide functionality. The core scaffold selection and the structure activity relationship development were supported by molecular modeling studies and by X-ray analysis of BACE1 complexes with various ligands to expedite the optimization of the series. The direct extension from P1-aryl- and heteroaryl moieties into the S3 binding pocket allowed the enhancement of potency and selectivity over cathepsin D. Restraining the design and synthesis of compounds to a physicochemical property space consistent with central nervous system drugs led to inhibitors with improved blood brain barrier permeability. Guided by structure-based optimization, we were able to obtain highly potent compounds such as 60p with enzymatic and cellular IC50 values of 2 and 50 nM, respectively, and with >200-fold selectivity over cathepsin D. Pharmacodynamic studies in APPS1/16 transgenic mice at oral doses of 180 mu mol/kg demonstrated significant reduction of brain A beta levels.

  DOI：

  10.1021/jm300069y
• 作为产物：
  描述：

  1,3-二溴-5-氟苯 在 sodium tetrahydroborate 、 正丁基锂 、 potassium tert-butylate 作用下， 以 乙醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.83h， 生成 (3-allyloxy-5-bromo-phenyl)methanol
  参考文献：
  名称：

  Discovery of Cyclic Sulfone Hydroxyethylamines as Potent and Selective β-Site APP-Cleaving Enzyme 1 (BACE1) Inhibitors: Structure-Based Design and in Vivo Reduction of Amyloid β-Peptides

  摘要：

  Structure-based design of a series of cyclic hydroxyethylamine BACE1 inhibitors allowed the rational incorporation of prime- and nonprime-side fragments to a central core template without any amide functionality. The core scaffold selection and the structure activity relationship development were supported by molecular modeling studies and by X-ray analysis of BACE1 complexes with various ligands to expedite the optimization of the series. The direct extension from P1-aryl- and heteroaryl moieties into the S3 binding pocket allowed the enhancement of potency and selectivity over cathepsin D. Restraining the design and synthesis of compounds to a physicochemical property space consistent with central nervous system drugs led to inhibitors with improved blood brain barrier permeability. Guided by structure-based optimization, we were able to obtain highly potent compounds such as 60p with enzymatic and cellular IC50 values of 2 and 50 nM, respectively, and with >200-fold selectivity over cathepsin D. Pharmacodynamic studies in APPS1/16 transgenic mice at oral doses of 180 mu mol/kg demonstrated significant reduction of brain A beta levels.

  DOI：

  10.1021/jm300069y

文献信息

• Versatile Bottom-up Approach to Stapled π-Conjugated Helical Scaffolds: Synthesis and Chiroptical Properties of Cyclic<i>o</i>-Phenylene Ethynylene Oligomers
  作者：Noelia Fuentes、Ana Martin-Lasanta、Luis Alvarez de Cienfuegos、Rafael Robles、Duane Choquesillo-Lazarte、Juan M. García-Ruiz、Lara Martínez-Fernández、Inés Corral、María Ribagorda、Antonio J. Mota、Diego J. Cárdenas、M. Carmen Carreño、Juan M. Cuerva

  DOI：10.1002/anie.201206259

  日期：2012.12.21

  loaded: The smallest members of a family of carbon nanocoils (CNCs), adopting a fixed helical structure, have been synthesized by introduction of one or two staples in o‐phenylene ethynylene oligomers. The chiroptical responses of the systems having enantiopure L‐tartrate‐derived staples confirmed the induced helicity. Theoretical studies suggest that these CNCs are pseudoelastic.

  弹簧加载：采用固定螺旋结构的碳纳米线圈（CNC）家族的最小成员，是通过在邻苯撑亚乙炔低聚物中引入一种或两种短钉而合成的。具有对映体纯的酒石酸L-酒石酸酯的钉书钉的系统的整脊反应证实了诱导的螺旋度。理论研究表明，这些CNC是伪弹性的。
• Discovery of Cyclic Sulfone Hydroxyethylamines as Potent and Selective β-Site APP-Cleaving Enzyme 1 (BACE1) Inhibitors: Structure-Based Design and in Vivo Reduction of Amyloid β-Peptides
  作者：Heinrich Rueeger、Rainer Lueoend、Olivier Rogel、Jean-Michel Rondeau、Henrik Möbitz、Rainer Machauer、Laura Jacobson、Matthias Staufenbiel、Sandrine Desrayaud、Ulf Neumann

  DOI：10.1021/jm300069y

  日期：2012.4.12

  Structure-based design of a series of cyclic hydroxyethylamine BACE1 inhibitors allowed the rational incorporation of prime- and nonprime-side fragments to a central core template without any amide functionality. The core scaffold selection and the structure activity relationship development were supported by molecular modeling studies and by X-ray analysis of BACE1 complexes with various ligands to expedite the optimization of the series. The direct extension from P1-aryl- and heteroaryl moieties into the S3 binding pocket allowed the enhancement of potency and selectivity over cathepsin D. Restraining the design and synthesis of compounds to a physicochemical property space consistent with central nervous system drugs led to inhibitors with improved blood brain barrier permeability. Guided by structure-based optimization, we were able to obtain highly potent compounds such as 60p with enzymatic and cellular IC50 values of 2 and 50 nM, respectively, and with >200-fold selectivity over cathepsin D. Pharmacodynamic studies in APPS1/16 transgenic mice at oral doses of 180 mu mol/kg demonstrated significant reduction of brain A beta levels.