5-chloro-7-(phenyl(pyridin-2-ylamino)methyl)quinolin-8-ol | 1203331-37-6

• 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: 5-chloro-7-(phenyl(pyridin-2-ylamino)methyl)quinolin-8-ol
• 英文别名: 5-Chloro-7-[phenyl(2-pyridinylamino)methyl]-8-quinolinol；5-chloro-7-[phenyl-(pyridin-2-ylamino)methyl]quinolin-8-ol
• CAS: 1203331-37-6
• 化学式: C₂₁H₁₆ClN₃O
• 分子量: 361.831
• InChiKey: LQXDDYGFBJHSFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  58
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-chloro-7-(phenyl(pyridin-2-ylamino)methyl)quinolin-8-ol 在 Chiralcel OD column 作用下， 生成 5-chloro-7-[(R)-phenyl-(pyridin-2-ylamino)methyl]quinolin-8-ol 、 5-chloro-7-[(S)-phenyl-(pyridin-2-ylamino)methyl]quinolin-8-ol
  参考文献：
  名称：

  Separation of Betti Reaction Product Enantiomers: Absolute Configuration and Inhibition of Botulinum Neurotoxin A

  摘要：

  The racemic product of the Betti reaction of 5-chloro-8-hydroxyquinoline, benzaldehyde, and 2-aminopyridine was separated by chiral HPLC to determine which enantiomer inhibited botulinurn neurotoxin serotype A. When the enantiomers unexpectedly proved to have comparable activity, the absolute structures of (+)-(R)-1 and ()-(S)-1 were determined by comparison of calculated and observed circular dichroism spectra. Molecular modeling studies were undertaken in an effort to understand the observed bioactivity and revealed different ensembles of binding modes, with roughly equal binding energies, for the two enantiomers.

  DOI：

  10.1021/ml200028z
• 作为产物：
  描述：

  2-氨基吡啶 、 苯甲醛 、 5-氯-8-羟基喹啉 以 乙醇 为溶剂， 以63%的产率得到5-chloro-7-(phenyl(pyridin-2-ylamino)methyl)quinolin-8-ol
  参考文献：
  名称：

  肉毒杆菌神经毒素血清型A的喹啉醇抑制剂的以基质为中心的结构活性和结合位点柔性研究

  摘要：

  我们最初发现的BoNT / A的8-羟基喹啉抑制剂和其中一种活性较高的对映体的对映异构体的分离/测试表明，其结合位点具有相当大的灵活性。我们设计了一项有限的研究来调查这种灵活性并探讨结构与活性之间的关系。利用Betti反应，使用三种8-羟基喹啉，三种杂芳族胺和四种取代的苯甲醛开发了一种36种喹啉基BoNT / A LC抑制剂的化合物基质。这项研究揭示了迄今为止一些最有效的基于喹啉醇的BoNT / A抑制剂，在离体测定中，有7种化合物的IC 50值⩽1μM和11种在⩽2μM时有效。

  DOI：

  10.1016/j.bmcl.2016.11.019

文献信息

• METHODS OF TREATING CREATINE TRANSPORTER DEFICIENCY
  申请人：Jnana Therapeutics, Inc.

  公开号：US20210299070A1

  公开（公告）日：2021-09-30

  Disclosed are methods of treating creatine transporter deficiency, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound that increases transport of a substrate by a mutant or wild-type creatine transporter. Also disclosed are methods of increasing transport of guanidinoacetic acid or a salt thereof across the blood-brain barrier of a mammal, and methods of decreasing accumulation or the concentration of guanidinoacetic acid or a salt thereof in a mammalian cell.

  揭示了治疗肌酸转运蛋白缺乏症的方法，包括向需要的哺乳动物施用增加突变型或野生型肌酸转运蛋白对底物转运的化合物的治疗有效量。还披露了增加鸟氨酸乙酸或其盐跨越哺乳动物血脑屏障的方法，以及减少哺乳动物细胞中鸟氨酸乙酸或其盐的积累或浓度的方法。
• SMALL MOLECULES TARGETING MUTANT MAMMALIAN PROTEINS
  申请人：Jnana Therapeutics, Inc.

  公开号：US20210300898A1

  公开（公告）日：2021-09-30

  Disclosed are compounds, compositions, and methods useful for treating or preventing a disease or disorder associated with a mutation in a protein.

  揭示了用于治疗或预防与蛋白质突变相关的疾病或紊乱的化合物、组合物和方法。
• A matrix-focused structure-activity and binding site flexibility study of quinolinol inhibitors of botulinum neurotoxin serotype A
  作者：William A. Harrell、Rebecca C. Vieira、Susan M. Ensel、Vicki Montgomery、Rebecca Guernieri、Vanessa S. Eccard、Yvette Campbell、Virginia Roxas-Duncan、John H. Cardellina、Robert P. Webb、Leonard A. Smith

  DOI：10.1016/j.bmcl.2016.11.019

  日期：2017.2

  considerable flexibility in the binding site. We designed a limited study to investigate this flexibility and probe structure-activity relationships; utilizing the Betti reaction, a 36 compound matrix of quinolinol BoNT/A LC inhibitors was developed using three 8-hydroxyquinolines, three heteroaromatic amines, and four substituted benzaldehydes. This study has revealed some of the most effective quinolinol-based

  我们最初发现的BoNT / A的8-羟基喹啉抑制剂和其中一种活性较高的对映体的对映异构体的分离/测试表明，其结合位点具有相当大的灵活性。我们设计了一项有限的研究来调查这种灵活性并探讨结构与活性之间的关系。利用Betti反应，使用三种8-羟基喹啉，三种杂芳族胺和四种取代的苯甲醛开发了一种36种喹啉基BoNT / A LC抑制剂的化合物基质。这项研究揭示了迄今为止一些最有效的基于喹啉醇的BoNT / A抑制剂，在离体测定中，有7种化合物的IC 50值⩽1μM和11种在⩽2μM时有效。
• Separation of Betti Reaction Product Enantiomers: Absolute Configuration and Inhibition of Botulinum Neurotoxin A
  作者：John H. Cardellina、Rebecca C. Vieira、Vanessa Eccard、Janet Skerry、Vicki Montgomery、Yvette Campbell、Virginia Roxas-Duncan、William Leister、Christopher A. LeClair、David J. Maloney、Daniele Padula、Gennaro Pescitelli、Ilja Khavrutskii、Xin Hu、Anders Wallqvist、Leonard A. Smith

  DOI：10.1021/ml200028z

  日期：2011.5.12

  The racemic product of the Betti reaction of 5-chloro-8-hydroxyquinoline, benzaldehyde, and 2-aminopyridine was separated by chiral HPLC to determine which enantiomer inhibited botulinurn neurotoxin serotype A. When the enantiomers unexpectedly proved to have comparable activity, the absolute structures of (+)-(R)-1 and ()-(S)-1 were determined by comparison of calculated and observed circular dichroism spectra. Molecular modeling studies were undertaken in an effort to understand the observed bioactivity and revealed different ensembles of binding modes, with roughly equal binding energies, for the two enantiomers.