1,2-dihydro-2-methyl-4-(2-methylphenyl)-1-oxo-3-isoquinolinecarboxylic acid | 152818-52-5

• 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: 1,2-dihydro-2-methyl-4-(2-methylphenyl)-1-oxo-3-isoquinolinecarboxylic acid
• 英文别名: 2-methyl-4-(2-methylphenyl)-1(2H)-isoquinolinone-3-carboxylic acid；2-Methyl-4-(2-methylphenyl)-1-oxoisoquinoline-3-carboxylic acid
• CAS: 152818-52-5
• 化学式: C₁₈H₁₅NO₃
• 分子量: 293.322
• InChiKey: JHOQAYXFLNTHPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,2-dihydro-2-methyl-4-(2-methylphenyl)-1-oxo-3-isoquinolinecarboxylic acid 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 N-(3,5-bistrifluoromethyl)benzyl-1,2-dihydro-2-methyl-4-(2-methylphenyl)-1-oxo-3-isoquinolinecarboxamide
  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-(2-甲基苯甲酰)苯甲酸 在 盐酸 、 sodium hydroxide 、 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 、 sodium nitrite 作用下， 以 乙醇 、 溶剂黄146 、 甲苯 为溶剂， 反应 8.5h， 生成 1,2-dihydro-2-methyl-4-(2-methylphenyl)-1-oxo-3-isoquinolinecarboxylic 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

文献信息

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

  公开号：US05482967A1

  公开（公告）日：1996-01-09

  Novel compound represented by the formula: ##STR1## such as 6-Chloro-N-(2,6-diethoxyphenyl)-4-(2-methylphenyl-2-oxo-2H-1-benzopyran-3- acetamide: ##STR2## or a salt thereof. The compound has an excellent activity of inhibiting ACAT, lowering the cholesterol in blood and inhibiting tachykinin receptor. The present invention also relates to the production and use of the disclosed compound.

  代表性化合物如6-氯-N-(2,6-二乙氧基苯基)-4-(2-甲基苯基-2-氧代-2H-1-苯并吡喃-3-基)乙酰胺，其化学式为：##STR1## 或其盐类。该化合物具有优异的抑制ACAT（酰基辅酶A胆固醇酰基转移酶）活性、降低血液胆固醇水平以及抑制速激肽受体的作用。本发明还涉及该化合物的制备方法及其应用。
• Tachykinin receptor antagonists, isoquinolones and their production
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：EP0566069A1

  公开（公告）日：1993-10-20

  Novel composition represented by the formula: wherein ring A and ring B each means a benzene ring which may be substituted; R means a hydrogen atom or an alkyl group which may be substituted; R¹ means a hydrogen atom or an alkyl group which may be substituted; R² means a hydrocarbon group which may be substituted or a heterocyclic group which may be substituted, or R¹ and R², taken together with the adjacent nitrogen atom, jointly form a ring which may be substituted, or a pharmaceutically acceptable salt thereof which is a useful tachykinin receptor antagonist.

  由式表示的新型组合物： 其中环 A 和环 B 各指一个可被取代的苯环；R 指一个氢原子或一个可被取代的烷基；R¹ 指一个氢原子或一个可被取代的烷基；R² 指一个可被取代的烃基或一个可被取代的杂环基，或 R¹ 和 R² 与相邻的氮原子共同形成一个可被取代的环，或其药学上可接受的盐，是一种有用的速激肽受体拮抗剂。
• US5482967A
  申请人：——

  公开号：US5482967A

  公开（公告）日：1996-01-09
• US5523305A
  申请人：——

  公开号：US5523305A

  公开（公告）日：1996-06-04
• US5700810A
  申请人：——

  公开号：US5700810A

  公开（公告）日：1997-12-23