5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)quinazolin-2-yl)pyridin-3-ylsulfonylphosphoramidic acid

• 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-ylmethyl)amino)quinazolin-2-yl)pyridin-3-ylsulfonylphosphoramidic acid
• 英文别名: 5-(5-Phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)pyridin-3-ylsulfonylphosphoramidic acid；[[5-[5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridin-3-yl]sulfonylamino]phosphonic acid
• 化学式: C₂₅H₂₁N₆O₅PS
• 分子量: 548.519
• InChiKey: LGUOZMZOKGTZSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  176
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)quinazolin-2-yl)pyridin-3-ylsulfonylphosphoramidic acid 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以85%的产率得到trisodium (5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)quinazolin-2-yl)pyridin-3-yl)sulfonylphosphoramidate
  参考文献：
  名称：

  [EN] PHOSPHORAMIDIC ACID PRODRUGS OF 5 - [5 - PHENYL- 4 - (PYRIDIN- 2 - YLMETHYLAMINO) QUINAZOLIN- 2 - YL] PYRIDINE- 3 - SULFONAMIDE
  [FR] PROMÉDICAMENTS D'ACIDE PHOSPHORAMIDIQUE DE 5-[5-PHÉNYL-4-(PYRIDIN-2-YLMÉTHYLAMINO)QUINAZOLIN-2-YLE]PYRIDINE-3-SULFONAMIDE

  摘要：

  其中R是H或-PO3H或其药物可接受的盐形式的化合物结构式(I)。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：

  WO2013188254A1
• 作为产物：
  描述：

  5-(5-苯基-4-((吡啶-2-甲基)氨基)喹唑啉-2-基)吡啶-3-磺酰胺 在 N,N-二异丙基乙胺 、 三氯氧磷 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 5.33h， 以77%的产率得到5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)quinazolin-2-yl)pyridin-3-ylsulfonylphosphoramidic acid
  参考文献：
  名称：

  [EN] PHOSPHORAMIDIC ACID PRODRUGS OF 5 - [5 - PHENYL- 4 - (PYRIDIN- 2 - YLMETHYLAMINO) QUINAZOLIN- 2 - YL] PYRIDINE- 3 - SULFONAMIDE
  [FR] PROMÉDICAMENTS D'ACIDE PHOSPHORAMIDIQUE DE 5-[5-PHÉNYL-4-(PYRIDIN-2-YLMÉTHYLAMINO)QUINAZOLIN-2-YLE]PYRIDINE-3-SULFONAMIDE

  摘要：

  其中R是H或-PO3H或其药物可接受的盐形式的化合物结构式(I)。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：

  WO2013188254A1

文献信息

• PHOSPHORAMIDIC ACID PRODRUGS OF 5-[5-PHENYL-4-(PYRIDIN-2-YLMETHYLAMINO)QUINAZOLIN-2-YL]PYRIDINE-3-SULFONAMIDE
  申请人：Bristol-Myers Squibb Company

  公开号：US20150175641A1

  公开（公告）日：2015-06-25

  A compound of structural formula (I), wherein R is H or —PO3H or a pharmaceutically acceptable salt form thereof. 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.

  结构式（I）的化合物，其中R为H或—PO3H或其药学上可接受的盐形式。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相关疾病和其他离子通道功能介导的疾病。
• Phosphoramidic acid prodrugs of 5-[5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl] pyridine-3-sulfonamide
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US09238666B2

  公开（公告）日：2016-01-19

  A compound of structural formula (I), wherein R is H or —PO3H or a pharmaceutically acceptable salt form thereof. 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.

  一种结构式（I）的化合物，其中R是H或—PO3H或其药学上可接受的盐形式。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相关疾病和其他离子通道功能介导的疾病。
• Selective <i>I</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
  作者：Prashantha Gunaga、John Lloyd、Somanadham Mummadi、Abhisek Banerjee、Naveen Kumar Dhondi、James Hennan、Veena Subray、Ramya Jayaram、Nagendra Rajugowda、Kommuri Umamaheshwar Reddy、Duraimurugan Kumaraguru、Umasankar Mandal、Dasthagiri Beldona、Ashok Kumar Adisechen、Navnath Yadav、Jayakumar Warrier、James A. Johnson、Harinath Sale、Siva Prasad Putlur、Ajay Saxena、Anjaneya Chimalakonda、Sandhya Mandlekar、MaryLee Conder、Dezhi Xing、Arun Kumar Gupta、Anuradha Gupta、Richard Rampulla、Arvind Mathur、Paul Levesque、Ruth R. Wexler、Heather J. Finlay

  DOI：10.1021/acs.jmedchem.6b01889

  日期：2017.5.11

  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.
• PHOSPHORAMIDIC ACID PRODRUGS OF 5 - [5 - PHENYL- 4 - (PYRIDIN- 2 - YLMETHYLAMINO) QUINAZOLIN- 2 - YL]PYRIDINE- 3 - SULFONAMIDE
  申请人：Bristol-Myers Squibb Company

  公开号：EP2858987A1

  公开（公告）日：2015-04-15
• US9238666B2
  申请人：——

  公开号：US9238666B2

  公开（公告）日：2016-01-19