1-(4-(fluorosulfonyl)benzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 1613052-75-7

• 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: 1-(4-(fluorosulfonyl)benzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 1-[(4-Fluorosulfonylphenyl)methyl]-4-oxoquinoline-3-carboxylic acid；1-[(4-fluorosulfonylphenyl)methyl]-4-oxoquinoline-3-carboxylic acid
• CAS: 1613052-75-7
• 化学式: C₁₇H₁₂FNO₅S
• 分子量: 361.35
• InChiKey: KPHXSYJAFDOSRG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  对甲基苯磺酰氟 在 N-溴代丁二酰亚胺(NBS) 、 N,N-二异丙基乙胺 、 过氧化苯甲酰 作用下， 以 乙酸乙酯 、 乙腈 为溶剂， 反应 22.5h， 生成 1-(4-(fluorosulfonyl)benzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of Analogues of Benzyl Quinolone Carboxylic Acid (BQCA) Designed to Bind Irreversibly to an Allosteric Site of the M₁ Muscarinic Acetylcholine Receptor

  摘要：

  Activation of the M1 muscarinic acetylcholine receptor (mAChR) is a prospective treatment for alleviating cognitive decline experienced in central nervous system (CNS) disorders. Current therapeutics indiscriminately enhance the activity of the endogenous neurotransmitter ACh, leading to side effects. BQCA is a positive allosteric modulator and allosteric agonist at the M1 mAChR that has high subtype selectivity and is a promising template from which to generate higher affinity, more pharmacokinetically viable drug candidates. However, to efficiently guide rational drug design, the binding site of BQCA needs to be conclusively elucidated. We report the synthesis and pharmacological validation of BQCA analogues designed to bind irreversibly to the M1 mAChR. One analogue in particular, 11, can serve as a useful structural probe to confirm the location of the BQCA binding site; ideally, by co-crystallization with the M1 mAChR. Furthermore, this ligand may also be used as a pharmacological tool with a range of applications.

  DOI：

  10.1021/jm500556a

文献信息

• Synthesis and Pharmacological Evaluation of Analogues of Benzyl Quinolone Carboxylic Acid (BQCA) Designed to Bind Irreversibly to an Allosteric Site of the M₁ Muscarinic Acetylcholine Receptor
  作者：Briana J. Davie、Celine Valant、Jonathan M. White、Patrick M. Sexton、Ben Capuano、Arthur Christopoulos、Peter J. Scammells

  DOI：10.1021/jm500556a

  日期：2014.6.26

  Activation of the M1 muscarinic acetylcholine receptor (mAChR) is a prospective treatment for alleviating cognitive decline experienced in central nervous system (CNS) disorders. Current therapeutics indiscriminately enhance the activity of the endogenous neurotransmitter ACh, leading to side effects. BQCA is a positive allosteric modulator and allosteric agonist at the M1 mAChR that has high subtype selectivity and is a promising template from which to generate higher affinity, more pharmacokinetically viable drug candidates. However, to efficiently guide rational drug design, the binding site of BQCA needs to be conclusively elucidated. We report the synthesis and pharmacological validation of BQCA analogues designed to bind irreversibly to the M1 mAChR. One analogue in particular, 11, can serve as a useful structural probe to confirm the location of the BQCA binding site; ideally, by co-crystallization with the M1 mAChR. Furthermore, this ligand may also be used as a pharmacological tool with a range of applications.