1,2-dihydro-2-methyl-1-oxo-4-phenyl-3-isoquinolineacetic acid | 167756-82-3

• 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: 1,2-dihydro-2-methyl-1-oxo-4-phenyl-3-isoquinolineacetic acid
• 英文别名: 1,2-Dihydro-2-methyl-1-oxo-4-phenyl-3-isoquinoline acetic acid；2-(2-methyl-1-oxo-4-phenylisoquinolin-3-yl)acetic acid
• CAS: 167756-82-3
• 化学式: C₁₈H₁₅NO₃
• 分子量: 293.322
• InChiKey: ZEAZIIAXTAKYOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  3
• 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-1-oxo-4-phenyl-3-isoquinolineacetic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 生成 2-(2-Methyl-1-oxo-4-phenylisoquinolin-3-yl)acetyl 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
• 作为产物：
  描述：

  1,2-dihydro-2-methyl-1-oxo-4-phenyl-1(2H)-isoquinolineacetonitrile 在 盐酸 、 溶剂黄146 作用下， 反应 8.0h， 以60%的产率得到1,2-dihydro-2-methyl-1-oxo-4-phenyl-3-isoquinolineacetic 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

• Isoquinolinyl compounds which are useful in treating cerebral vascular
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05527811A1

  公开（公告）日：1996-06-18

  Compounds represented by the formula: ##STR1## wherein the ring A and the ring B each stand for an optionally substituted benzene ring; Ar stands for an optionally substituted aryl group or an optionally substituted heterocyclic group; Q stands for an oxygen atom or a sulfur atom; R stands for a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group or an optionally substituted amino group; X stands for --O-- or --NR.sup.1 -- wherein R.sup.1 stands for a hydrogen atom or an optionally substituted hydrocarbon group; Y stands for --O--, --NR.sup.2 -- wherein R.sup.2 stands for a hydrogen atom or an optionally substituted hydrocarbon group, or a bond; m denotes 1, 2 or 3, and n denotes 0, 1 or 2, and salts thereof which have excellent calcium- or substance P receptor-antagonistic activity, being useful for treating a cerebralvascular disorder in mammals such as cerebralischemia, cerebral edema and neuronal damage, their production and use.

  化合物的公式为：##STR1## 其中环A和环B分别代表可选取代的苯环；Ar代表可选取代的芳基基团或可选取代的杂环基团；Q代表氧原子或硫原子；R代表氢原子、可选取代的碳氢基团、可选取代的羟基或可选取代的氨基基团；X代表--O--或--NR.sup.1 --，其中R.sup.1代表氢原子或可选取代的碳氢基团；Y代表--O--、--NR.sup.2 --，其中R.sup.2代表氢原子或可选取代的碳氢基团，或一个键；m为1、2或3，n为0、1或2，以及具有优异的钙或物质P受体拮抗活性的盐，用于治疗哺乳动物的脑血管疾病，如脑缺血、脑水肿和神经元损伤，其制备和使用。
• Isochinolinone derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0634402A1

  公开（公告）日：1995-01-18

  Novel compounds represented by the formula: wherein the ring A and the ring B each stand for an optionally substituted benzene ring; Ar stands for an optionally substituted aryl group or an optionally substituted heterocyclic group; Q stands for an oxygen atom or a sulfur atom; R stands for a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group or an optionally substituted amino group; X stands for -O- or -NR¹- wherein R¹ stands for a hydrogen atom or an optionally substituted hydrocarbon group; Y stands for -O-, -NR²- wherein R² stands for a hydrogen atom or an optionally substituted hydrocarbon group, or a bond; m denotes 1, 2 or 3, and n denotes 0, 1 or 2, and salts thereof which have an excellent calcium- or substance P receptor-antagonistic activity, being useful for treating a cerebralvascular disorder in mammals such as cerebralischemia, cerebral edema and neuronal damage, their production and use.

  式所代表的新型化合物： 其中环 A 和环 B 各代表一个任选取代的苯环； Ar 代表任选取代的芳基或任选取代的杂环基团； Q 代表氧原子或硫原子； R 代表氢原子、任选取代的烃基、任选取代的羟基或任选取代的氨基； X 代表-O-或-NR¹-，其中 R¹ 代表氢原子或任选取代的烃基； Y 代表-O-、-NR²-（其中 R² 代表氢原子或任选取代的烃基）或键； m 表示 1、2 或 3，以及 n 表示 0、1 或 2，及其盐类，它们具有优异的钙或 P 物质受体拮抗活性，可用于治疗哺乳动物的脑血管疾病，如脑缺血、脑水肿和神经元损伤。
• US5527811A
  申请人：——

  公开号：US5527811A

  公开（公告）日：1996-06-18
• 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.