3-(4-Fluorobenzoyl)pyridine-2-carbonyl chloride | 168543-08-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(4-Fluorobenzoyl)pyridine-2-carbonyl chloride
• CAS: 168543-08-6
• 化学式: C₁₃H₇ClFNO₂
• 分子量: 263.655
• InChiKey: AHIGTFNBPSNDOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  47
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-Fluorobenzoyl)pyridine-2-carbonyl chloride 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 12.0h， 生成 benzyl 5-(4-fluorophenyl)-7,8-dihydro-7-methyl-8-oxo-6-pyrido<3,4-b>pyridinecarboxylate
  参考文献：
  名称：

  Novel, Potent, and Orally Active Substance P Antagonists: Synthesis and Antagonist Activity of N-Benzylcarboxamide Derivatives of Pyrido[3,4-b]pyridine

  摘要：

  A series of 4-phenylisoquinolone derivatives were synthesized and evaluated for NK1 (substance P) antagonist activity. Highly potent antagonists, 4-phenyl-3-isoquinolone-N-benzylcarboxamides (11), were discovered from the structure-activity relationship studies on the isoquinolone-urea lead la. Optimization of the activity in this series resulted in the development of 5-phenyl-6-pyrido[3,4-b]pyridine-N-benzylcarboxamides (30) which are highly potent orally active NK1 antagonists. Among the compounds synthesized, N-[3,5-bis(trifluoromethyl)benzyl]7,8-dihydro-N, 7-dimethyl-8-oxo-5-(substituted phenyl)6-pyrido[3,4-b]pyridinecarboxamides (30a,f,g) showed excellent antagonist activities with IC50 values (in vitro inhibition of [I-125]- BH-SP binding in human IM-9 cells) of 0.21-0.34 nM and ED(50) values (in vivo inhibition of capsaicin-induced plasma extravasation in guinea-pig trachea, iv) of 0.017-0.030 mg/kg. These compounds exhibited significantly potent activity upon oral administration with ED(50) values of 0.068-0.17 mg/kg. Conformational studies on 30g indicated that the two stable conformers of 30g are quite similar to those of CP-99,994.

  DOI：

  10.1021/jm00016a014
• 作为产物：
  描述：

  2,3-吡啶二羧酸酐 在 三氯化铝 、 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 3-(4-Fluorobenzoyl)pyridine-2-carbonyl chloride
  参考文献：
  名称：

  Novel, Potent, and Orally Active Substance P Antagonists: Synthesis and Antagonist Activity of N-Benzylcarboxamide Derivatives of Pyrido[3,4-b]pyridine

  摘要：

  A series of 4-phenylisoquinolone derivatives were synthesized and evaluated for NK1 (substance P) antagonist activity. Highly potent antagonists, 4-phenyl-3-isoquinolone-N-benzylcarboxamides (11), were discovered from the structure-activity relationship studies on the isoquinolone-urea lead la. Optimization of the activity in this series resulted in the development of 5-phenyl-6-pyrido[3,4-b]pyridine-N-benzylcarboxamides (30) which are highly potent orally active NK1 antagonists. Among the compounds synthesized, N-[3,5-bis(trifluoromethyl)benzyl]7,8-dihydro-N, 7-dimethyl-8-oxo-5-(substituted phenyl)6-pyrido[3,4-b]pyridinecarboxamides (30a,f,g) showed excellent antagonist activities with IC50 values (in vitro inhibition of [I-125]- BH-SP binding in human IM-9 cells) of 0.21-0.34 nM and ED(50) values (in vivo inhibition of capsaicin-induced plasma extravasation in guinea-pig trachea, iv) of 0.017-0.030 mg/kg. These compounds exhibited significantly potent activity upon oral administration with ED(50) values of 0.068-0.17 mg/kg. Conformational studies on 30g indicated that the two stable conformers of 30g are quite similar to those of CP-99,994.

  DOI：

  10.1021/jm00016a014

文献信息

• Novel, Potent, and Orally Active Substance P Antagonists: Synthesis and Antagonist Activity of N-Benzylcarboxamide Derivatives of Pyrido[3,4-b]pyridine
  作者：Hideaki Natsugari、Yoshinori Ikeura、Yutaka Kiyota、Yuji Ishichi、Takenori Ishimaru、Osamu Saga、Hideo Shirafuji、Toshimasa Tanaka、Izumi Kamo

  DOI：10.1021/jm00016a014

  日期：1995.8

  A series of 4-phenylisoquinolone derivatives were synthesized and evaluated for NK1 (substance P) antagonist activity. Highly potent antagonists, 4-phenyl-3-isoquinolone-N-benzylcarboxamides (11), were discovered from the structure-activity relationship studies on the isoquinolone-urea lead la. Optimization of the activity in this series resulted in the development of 5-phenyl-6-pyrido[3,4-b]pyridine-N-benzylcarboxamides (30) which are highly potent orally active NK1 antagonists. Among the compounds synthesized, N-[3,5-bis(trifluoromethyl)benzyl]7,8-dihydro-N, 7-dimethyl-8-oxo-5-(substituted phenyl)6-pyrido[3,4-b]pyridinecarboxamides (30a,f,g) showed excellent antagonist activities with IC50 values (in vitro inhibition of [I-125]- BH-SP binding in human IM-9 cells) of 0.21-0.34 nM and ED(50) values (in vivo inhibition of capsaicin-induced plasma extravasation in guinea-pig trachea, iv) of 0.017-0.030 mg/kg. These compounds exhibited significantly potent activity upon oral administration with ED(50) values of 0.068-0.17 mg/kg. Conformational studies on 30g indicated that the two stable conformers of 30g are quite similar to those of CP-99,994.