5-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)nicotinonitrile | 1272354-22-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)nicotinonitrile
• 英文别名: 5-[5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-carbonitrile
• CAS: 1272354-22-9
• 化学式: C₂₆H₁₈N₆
• 分子量: 414.469
• InChiKey: GZTPXCYZUKETMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  87.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)nicotinonitrile 在 盐酸羟胺 、 potassium carbonate 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 35.5h， 生成 tert-butyl 1-(3-(5-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)pyridin-3-yl)-1,2,4-oxadiazole-5-carbonyl)piperidin-4-ylcarbamate
  参考文献：
  名称：

  [EN] QUINAZOLINES AS POTASSIUM ION CHANNEL INHIBITORS
  [FR] QUINAZOLINES COMME INHIBITEURS DES CANAUX IONIQUES POTASSIQUES

  摘要：

  其中A、X、Y、Z、R1和R24如所述的(I)式化合物。这些化合物作为钾通道功能的抑制剂以及用于治疗和预防心律不齐、IKur相关疾病和其他由离子通道功能介导的疾病是有用的。

  公开号：

  WO2011028741A1
• 作为产物：
  描述：

  3-氰基吡啶-5-硼酸频哪醇酯 、 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以79.2%的产率得到5-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)nicotinonitrile
  参考文献：
  名称：

  Selective I_Kur Inhibitors for the Potential Treatment of Atrial Fibrillation: Optimization of the Phenyl Quinazoline Series Leading to Clinical Candidate 5-[5-Phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide

  摘要：

  We have recently disclosed 5-phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine 1 as a potent I-Kur current blocker with selectivity versus hERG, Na and Ca channels, and an acceptable preclinical PK profile. Upon further characterization in vivo, compound 1 demonstrated an unacceptable level of brain penetration. In an effort to reduce the level of brain penetration while maintaining the overall profile, SAR was developed at the C2' position for a series of close analogues by employing hydrogen bond donors. As a result, 5-[5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide (25) was identified as the lead compound in this series. Compound 25 showed robust effects in rabbit and canine pharmacodynamic models and an acceptable cross-species pharmacokinetic profile and was advanced as the clinical candidate. Further optimization of 25 to mitigate pH-dependent absorption resulted in identification of the corresponding phosphoramide prodrug (29) with an improved solubility and pharmacokinetic profile.

  DOI：

  10.1021/acs.jmedchem.6b01889

文献信息

• QUINAZOLINES AS POTASSIUM ION CHANNEL INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：US20140031345A1

  公开（公告）日：2014-01-30

  A compound of formula I wherein A, X, Y, Z, R 1 and R 24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, I Kur -associated disorders, and other disorders mediated by ion channel function.

  化合物I的化学式如下，其中A，X，Y，Z，R1和R24的描述在此处。这些化合物可用作钾通道功能的抑制剂，并用于治疗和预防心律失常，IKur相关疾病以及其他离子通道功能介导的疾病。
• Quinazolines as potassium ion channel inhibitors
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US10676460B2

  公开（公告）日：2020-06-09

  A compound of formula I wherein A, X, Y, Z, R1 and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

  式 I 的化合物 其中 A、X、Y、Z、R1 和 R24 如本文所述。这些化合物可作为钾离子通道功能的抑制剂，用于治疗和预防心律失常、IKur 相关性疾病和其他由离子通道功能介导的疾病。
• US8575184B2
  申请人：——

  公开号：US8575184B2

  公开（公告）日：2013-11-05
• US9458114B2
  申请人：——

  公开号：US9458114B2

  公开（公告）日：2016-10-04
• US9822096B2
  申请人：——

  公开号：US9822096B2

  公开（公告）日：2017-11-21