benzyl 5-(4-fluorophenyl)-7,8-dihydro-7-methyl-8-oxo-6-pyrido<3,4-b>pyridinecarboxylate | 168541-95-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: benzyl 5-(4-fluorophenyl)-7,8-dihydro-7-methyl-8-oxo-6-pyrido<3,4-b>pyridinecarboxylate
• 英文别名: 5-(4-fluorophenyl)-7,8-dihydro-7-methyl-8-oxo-6-pyrido[3,4-b]pyridinecarboxylic acid benzyl ester；Benzyl 5-(4-fluorophenyl)-7-methyl-8-oxo-1,7-naphthyridine-6-carboxylate
• CAS: 168541-95-5
• 化学式: C₂₃H₁₇FN₂O₃
• 分子量: 388.398
• InChiKey: KJSQXLSJIIYZRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  59.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl 5-(4-fluorophenyl)-7,8-dihydro-7-methyl-8-oxo-6-pyrido<3,4-b>pyridinecarboxylate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以85%的产率得到5-(4-fluorophenyl)-7,8-dihydro-7-methyl-8-oxo-6-pyrido<3,4-b>pyridinecarboxylic acid
  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 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 17.0h， 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

文献信息

• Heterocyclic compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0652218A1

  公开（公告）日：1995-05-10

  A novel compound represented by the formula: wherein Ring A and Ring B respectively stands for an optionally substituted homo- or hetero-cyclic ring, and at least one of them stands for an optionally substituted heterocyclic ring stand; Ring C stands for an optionally substituted benzene ring; R stands for a hydrogen atom or an optionally substituted hydrocarbon residue; one of X and Y stands for -NR¹- (R¹ stands for a hydrogen atom or an optionally substituted hydrocarbon residue) or -O-, and the other stands for - CO- or -CS-, or one of them stands for -N= and the other stands for =CR²- (R² stands for a hydrogen atom, a halogen atom, an optionally substituted hydrocarbon residue, an optionally substituted amino group or an optionally substituted hydroxyl group); n denotes 1 or 2 or salts thereof which have an excellent tachykinin receptor antagonistic action and inhibitory action on plasma extravasation.

  一种由式表示的新型化合物： 其中，环 A 和环 B 分别代表任选取代的同环或杂环，其中至少一个代表任选取代的杂环；环 C 代表任选取代的苯环；R 代表氢原子或任选取代的烃残基；X和Y中的一个代表-NR¹-（R¹代表氢原子或任选取代的烃残基）或-O-，另一个代表-CO-或-CS-，或其中一个代表-N=，另一个代表=CR²-（R²代表氢原子、卤素原子、任选取代的烃残基、任选取代的氨基或任选取代的羟基）；n 表示 1 或 2 或其盐类，它们具有优异的速激肽受体拮抗作用和血浆外渗抑制作用。
• US5585385A
  申请人：——

  公开号：US5585385A

  公开（公告）日：1996-12-17
• 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.