3-Quinolineacryloyl chloride | 767260-77-5

• 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: 3-Quinolineacryloyl chloride
• 英文别名: 3-quinolin-3-ylprop-2-enoyl chloride
• CAS: 767260-77-5
• 化学式: C₁₂H₈ClNO
• 分子量: 217.655
• InChiKey: KXPUPIICYPCPLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-Quinolineacryloyl chloride 在 palladium on activated charcoal 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 dichlorormethane 为溶剂， 反应 3.17h， 生成 N-cyclohexyl-N-methyl-3-quinolin-3-ylpropanamide
  参考文献：
  名称：

  From Fragment Screening to In Vivo Efficacy: Optimization of a Series of 2-Aminoquinolines as Potent Inhibitors of Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1)

  摘要：

  Using fragment-based screening of a focused fragment library, 2-aminoquinoline I was identified as an initial hit for BACE1. Further SAR development was supported by X-ray structures of BACE1 cocrystallized with various ligands and molecular modeling studies to expedite the discovery of potent compounds. These strategies enabled us to integrate the C-3 side chain on 2-aminoquinoline 1 extending deep into the P2' binding pocket of BACE1 and enhancing the ligand's potency. We were able to improve the BACE1 potency to subnanomolar range, over 10(6)-fold more potent than the initial hit (900 mu M). Further elaboration of the physical properties of the lead compounds to those more consistent with good blood-brain barrier permeability led to inhibitors with greatly improved cellular activity and permeability. Compound 59 showed an IC50 value of 11 nM on BACE1 and cellular activity of 80 nM, This compound was advanced into rat pharmacokinetic and pharmacodynamic studies and demonstrated significant reduction of A beta levels in cerebrospinal fluid (CSF).

  DOI：

  10.1021/jm200544q
• 作为产物：
  描述：

  3-(quinolin-3-yl)acrylic acid 在 氯化亚砜 作用下， 反应 1.5h， 生成 3-Quinolineacryloyl chloride
  参考文献：
  名称：

  From Fragment Screening to In Vivo Efficacy: Optimization of a Series of 2-Aminoquinolines as Potent Inhibitors of Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1)

  摘要：

  Using fragment-based screening of a focused fragment library, 2-aminoquinoline I was identified as an initial hit for BACE1. Further SAR development was supported by X-ray structures of BACE1 cocrystallized with various ligands and molecular modeling studies to expedite the discovery of potent compounds. These strategies enabled us to integrate the C-3 side chain on 2-aminoquinoline 1 extending deep into the P2' binding pocket of BACE1 and enhancing the ligand's potency. We were able to improve the BACE1 potency to subnanomolar range, over 10(6)-fold more potent than the initial hit (900 mu M). Further elaboration of the physical properties of the lead compounds to those more consistent with good blood-brain barrier permeability led to inhibitors with greatly improved cellular activity and permeability. Compound 59 showed an IC50 value of 11 nM on BACE1 and cellular activity of 80 nM, This compound was advanced into rat pharmacokinetic and pharmacodynamic studies and demonstrated significant reduction of A beta levels in cerebrospinal fluid (CSF).

  DOI：

  10.1021/jm200544q

文献信息

• Pyridine derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05246948A1

  公开（公告）日：1993-09-21

  There is disclosed a pharmaceutical composition for providing antiinflammatory, antipyretic, analgesic, antiallergic, immunosuppressing or immunomodulating activity which comprises a pyridine derivative of the formula (I): ##STR1## wherein R is an optionally substituted pyridine ring, X is a oxygen atom or --S(O)n--, wherein n is 0, 1 or 2, A is a bivalent C.sub.1-15 hydrocarbon residue whose branched moiety may have a substituent, Y is an oxygen or sulfur atom, R.sub.3 is a hydrogen atom or an optionally substituted hydrocarbon residue, R.sub.4 is an optionally substituted hydrocarbon residue or an optionally substituted monocyclic or bicyclic heterocyclic group, R.sub.3 and R.sub.4 may be joined together with the carbamoyl group or the thiocarbamoyl group to which they are attached to form an optionally substituted heterocyclic group, or R.sub.3 or R.sub.4 may be independently attached to A to form a ring, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier or diluent.

  本发明揭示了一种药物组合物，用于提供抗炎、退热、镇痛、抗过敏、免疫抑制或免疫调节活性，其包含式（I）的吡啶衍生物：##STR1## 其中，R是可选取代的吡啶环，X是氧原子或--S（O）n--，其中n为0、1或2，A是二价的C.sub.1-15烃基残基，其支链部分可能有取代基，Y是氧或硫原子，R.sub.3是氢原子或可选取代的烃基残基，R.sub.4是可选取代的烃基残基或可选取代的单环或双环杂环基，R.sub.3和R.sub.4可与它们附着的氨基甲酰基或硫氨基甲酰基结合在一起，形成可选取代的杂环基，或R.sub.3或R.sub.4可独立地附着在A上形成环，或其药学上可接受的盐或溶剂，以及药学上可接受的载体或稀释剂。