2(1H)-喹啉酮,3,4-二氢-6-(3-吡啶基乙炔基)- | 120067-82-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 2(1H)-喹啉酮,3,4-二氢-6-(3-吡啶基乙炔基)-
• 英文名称: 6-[2-(pyridin-3-yl)ethynyl]-3,4-dihydrocarbostyril
• 英文别名: 6-[2-(3-pyridyl)ethynyl]-3,4-dihydrocarbostyril；6-(2-pyridin-3-ylethynyl)-3,4-dihydro-1H-quinolin-2-one
• CAS: 120067-82-5
• 化学式: C₁₆H₁₂N₂O
• 分子量: 248.284
• InChiKey: LMUOBICMEAOSLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2(1H)-喹啉酮,3,4-二氢-6-(3-吡啶基乙炔基)- 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 以965 mg的产率得到6-(2-Pyridin-3-yl-ethyl)-3,4-dihydro-1H-quinolin-2-one
  参考文献：
  名称：

  3,4-Dihydroquinolin-2(1H)-ones as combined inhibitors of thromboxane A2 synthase and cAMP phosphodiesterase

  摘要：

  A series of 1H-imidazol-1-yl- and 3-pyridyl-substituted 3,4-dihydroquinolin-2(1H)-ones was designed and synthesized as combined inhibitors of thromboxane (TXA2) synthase and cAMP phosphodiesterase (PDE) in human blood platelets. A number of structures, e.g. 4b, 7a, 7e, 13a, and 21-25, were superior to dazoxiben 26 as inhibitors of TXA2 synthase in in vitro ADP-induced aggregation experiments with human blood platelets. The TXA2 synthase inhibitory activity was confirmed by measurement of the prostanoid metabolites derived from C-14-labeled arachidonic acid. Three compounds (7a, 7e, and 25) demonstrated in vitro inhibition of human platelet cAMP PDE at micromolar concentrations in conjunction with their TXA2 synthase inhibitory activity. Synergistic enhancement of antiaggregatory and antithrombotic actions was expected when simultaneous stimulation of adenylate cyclase (through increased PGI2 production) and inhibition of platelet cAMP PDE were possible from the same compound. Ex vivo and in vivo experiments were conducted in rats and mice, respectively, to evaluate the effects of compounds 7e and 23 on platelet aggregation and thrombotic events within these animals. Compound 7e, which has a comparable level of TXA2 synthase (IC50 1.2-mu-M) and human platelet cAMP PDE (IC50 6.4-mu-M) inhibitory activities, was found to be orally bioavailable with a long duration of action and offered effective protection against mortality in a collagen-epinephrine-induced pulmonary thromboembolism model in mice. Significant blood pressure and heart rate effects were observed for several compounds, e.g. 7e, 9e, 13a, 13d, 18, 20, 21, and 23, when dosed orally in conscious spontaneously hypertensive rats.

  DOI：

  10.1021/jm00082a002
• 作为产物：
  描述：

  3,4-二氢-2(1H)-喹啉酮 在 bis-triphenylphosphine-palladium(II) chloride 、 N-溴代丁二酰亚胺(NBS) 、 copper(l) iodide 、 potassium carbonate 作用下， 以 吡啶 、 甲醇 、 三乙胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 162.25h， 生成 2(1H)-喹啉酮,3,4-二氢-6-(3-吡啶基乙炔基)-
  参考文献：
  名称：

  3,4-Dihydroquinolin-2(1H)-ones as combined inhibitors of thromboxane A2 synthase and cAMP phosphodiesterase

  摘要：

  A series of 1H-imidazol-1-yl- and 3-pyridyl-substituted 3,4-dihydroquinolin-2(1H)-ones was designed and synthesized as combined inhibitors of thromboxane (TXA2) synthase and cAMP phosphodiesterase (PDE) in human blood platelets. A number of structures, e.g. 4b, 7a, 7e, 13a, and 21-25, were superior to dazoxiben 26 as inhibitors of TXA2 synthase in in vitro ADP-induced aggregation experiments with human blood platelets. The TXA2 synthase inhibitory activity was confirmed by measurement of the prostanoid metabolites derived from C-14-labeled arachidonic acid. Three compounds (7a, 7e, and 25) demonstrated in vitro inhibition of human platelet cAMP PDE at micromolar concentrations in conjunction with their TXA2 synthase inhibitory activity. Synergistic enhancement of antiaggregatory and antithrombotic actions was expected when simultaneous stimulation of adenylate cyclase (through increased PGI2 production) and inhibition of platelet cAMP PDE were possible from the same compound. Ex vivo and in vivo experiments were conducted in rats and mice, respectively, to evaluate the effects of compounds 7e and 23 on platelet aggregation and thrombotic events within these animals. Compound 7e, which has a comparable level of TXA2 synthase (IC50 1.2-mu-M) and human platelet cAMP PDE (IC50 6.4-mu-M) inhibitory activities, was found to be orally bioavailable with a long duration of action and offered effective protection against mortality in a collagen-epinephrine-induced pulmonary thromboembolism model in mice. Significant blood pressure and heart rate effects were observed for several compounds, e.g. 7e, 9e, 13a, 13d, 18, 20, 21, and 23, when dosed orally in conscious spontaneously hypertensive rats.

  DOI：

  10.1021/jm00082a002

文献信息

• Carbostyril derivatives as combined thromboxane synthetase and
  申请人：Syntex (U.S.A.) Inc.

  公开号：US04792561A1

  公开（公告）日：1988-12-20

  The invention concerns a method of inhibiting both thromboxane synthetase and cyclic-AMP phosphodiesterase in a mammal having a disease characterized by elevated thromboxane levels or an imbalance of prostacyclin/thromboxane levels with a compound of the formula: ##STR1## or a pharmaceutically acceptable acid addition salt or ester thereof, wherein: X is chosen from the group consisting of: ##STR2## and a covalent bond in which R.sup.1 is H, alkyl having 1-6 carbon atoms, optionally substituted phenyl or optionally substituted phenyl lower alkyl, when R.sup.2 is H or OH, or R.sup.1 and R.sup.2 taken together represent oxo, alkylidene having 1-6 carbon atoms or optionally substituted benzylidene; R.sup.3 is H or alkyl having 1-6 carbon atoms, R.sup.4 is H and R.sup.3 and R.sup.4 are either cis or trans to each other, or R.sup.3 and R.sup.4 taken together represent a covalent bond; n is an integer from 0-3; Het is 1-imidazolyl or 3-pyridyl; and the dotted line represents an optional covalent bond.

  该发明涉及一种抑制哺乳动物体内同时具有高血栓素水平或前列环素/血栓素水平失衡的疾病的方法，所使用的化合物具有以下结构式：X选自以下组合之一：和一个共价键，其中R.sup.1为H、具有1-6个碳原子的烷基、可选择取代的苯基或可选择取代的苯基较低烷基，当R.sup.2为H或OH时，或者R.sup.1和R.sup.2一起代表氧代、具有1-6个碳原子的烷基亚甲基或可选择取代的苄亚甲基；R.sup.3为H或具有1-6个碳原子的烷基，R.sup.4为H且R.sup.3和R.sup.4要么相对构型，要么相对构型，或者R.sup.3和R.sup.4一起代表一个共价键；n为0-3的整数；Het为1-咪唑基或3-吡啶基；虚线代表可选择的共价键。
• WALKER, KEITH A. M.;BRUNO, JOHN J.;MARTINEZ, GREGORY R.
  作者：WALKER, KEITH A. M.、BRUNO, JOHN J.、MARTINEZ, GREGORY R.

  DOI：——

  日期：——
• US4792561A
  申请人：——

  公开号：US4792561A

  公开（公告）日：1988-12-20
• US4921862A
  申请人：——

  公开号：US4921862A

  公开（公告）日：1990-05-01