2,6,7-Trimethyl-1-oxo-4-phenylisoquinoline-3-carbonyl chloride | 1026233-53-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2,6,7-Trimethyl-1-oxo-4-phenylisoquinoline-3-carbonyl chloride
• CAS: 1026233-53-3
• 化学式: C₁₉H₁₆ClNO₂
• 分子量: 325.795
• InChiKey: LTKSKGIWPMSSQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,6,7-Trimethyl-1-oxo-4-phenylisoquinoline-3-carbonyl chloride 在 sodium tetrahydroborate 、 三乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 0.75h， 生成 1,2-Dihydro-3-methanesulfonyloxymethyl-2,6,7-trimethyl-1-oxo-4-phenylisoquinoline
  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-benzoyl-4,5-dimethylbenzoic acid 在 盐酸 、 (COCl₂)2 、 potassium carbonate 、 溶剂黄146 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 69.5h， 生成 2,6,7-Trimethyl-1-oxo-4-phenylisoquinoline-3-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.