6-(2,3-epoxypropoxy)-2(1H)-quinolinone | 128668-84-8

• 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
• 英文名称: 6-(2,3-epoxypropoxy)-2(1H)-quinolinone
• 英文别名: R-6-(2,3-epoxypropoxy)carbostyril；6-(Oxiran-2-ylmethoxy)quinolin-2(1H)-one；6-(oxiran-2-ylmethoxy)-1H-quinolin-2-one
• CAS: 128668-84-8
• 化学式: C₁₂H₁₁NO₃
• 分子量: 217.224
• InChiKey: DUPCWZHIWASNPP-UHFFFAOYSA-N

物化性质

• 沸点：
  467.9±45.0 °C(Predicted)
• 密度：
  1.305±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  50.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(2,3-epoxypropoxy)-2(1H)-quinolinone 生成 R-(+)-6-[3-(N-methyl-N-benzylamino)-2-hydroxypropoxy]carbostyril
  参考文献：
  名称：

  Cardiotonics

  摘要：

  本发明涉及使用公式为：##STR1##其中R.sup.1为H或CN，R.sup.2和R.sup.3分别为H，烷基（其上可选择性地取代为OH），环烷基，烯基，苯基，苯基烷基，其上可选择性地有取代基的烷氧基烷氧基，卤素，烷氧基，NO.sub.2，烷基，CN，烷硫基或烷基亚砜基，其在苯环上具有可选择性的OH取代基的烷基部分，苯基磺酰基烷基，其在苯环上具有可选择性的烷氧基取代基的苯基磺酰基烷基，苯基硫基烷基，苯基亚砜基烷基，其在苯环上具有可选择性的卤素或烷氧基取代基的苯基亚砜基烷基，苯氧基烷基，其在苯环上具有可选择性的卤素或烷氧基取代基的苯氧基烷基，吡啶基烷基，其在吡啶环上具有可选择性的卤素或烷氧基取代基，噻吩基烷基，苯甲酰基烷基，苯胺硫代氨基甲酰基，苯甲酰基，吡啶基，苯基烯基，或--A-NR.sup.4 R.sup.5（其中R.sup.4和R.sup.5分别为烷基或苯基，其在苯环上具有可选择性的卤素或烷氧基取代基，A为可用O中断的烷基），以及其盐的预防和治疗心脏疾病的方法，以及新的卡波斯蒂瑞尔衍生物和含有所述新的卡波斯蒂瑞尔衍生物的预防和治疗心脏疾病的药物组合物。

  公开号：

  US05198448A1
• 作为产物：
  描述：

  R-6-(3-chloro-2-hydroxypropoxy)carbostyril 以67的产率得到6-(2,3-epoxypropoxy)-2(1H)-quinolinone
  参考文献：
  名称：

  Chem. Pharm. Bull. 1996, 44, 1596-1598

  摘要：

  DOI：

文献信息

• Cardiotonic carbostyril agents for treating heart ailments
  申请人：Otsuka Pharmaceutical Company, Limited

  公开号：US05385914A1

  公开（公告）日：1995-01-31

  Method for prophylaxis and treatment of heart diseases using a carbostyril derivative-of formula: ##STR1## wherein R.sup.1 is H or CN, and R.sup.2 and R.sup.3 are each H, alkyl optionally substituted by OH, cycloalkyl, alkenyl, phenyl, phenylalkyl having optionally substituents of alkoxyalkoxy, halogen, alkoxy, NO.sub.2, alkyl, CN, alkylthio or alkylsulfinyl on phenyl ring and having optionally OH-substituent on alkyl moiety, phenylsulfonylalkyl having optionally alkoxy substituent on phenyl ring, phenylthioalkyl, phenylsulfinylalkyl having optionally substituents of halogen or alkoxy on phenyl ring, phenoxyalkyl having optionally substituents of halogen or alkoxy on phenyl ring, pyridylalkyl having optionally substituents of halogen or alkoxy on pyridine ring, thienylalkyl, benzoylalkyl, anilinothiocarbonyl, benzoyl, pyridyl, phenylalkenyl, or group of --A--NR.sup.4 R.sup.5 (R.sup.4 and R.sup.5 are each alkyl or phenyl having optionally substituents of halogen or alkoxy on phenyl ring, and A is alkylene which may be interrupted with O), and a salt thereof, and novel carbostyril derivatives, and pharmaceutical composition for prophylaxis and treatment of heart diseases containing said novel carbostyril derivative.

  使用一种羧基苯基吡啶衍生物的方法预防和治疗心脏疾病，其化学式为：##STR1## 其中R.sup.1为H或CN，R.sup.2和R.sup.3分别为H，烷基（可选用OH取代），环烷基，烯基，苯基，苯基烷基，在苯环上可选地带有烷氧基烷氧基，卤素，烷氧基，NO.sub.2，烷基，CN，烷硫基或烷基磺酰基取代基，并在烷基部分上可选地带有OH取代基，苯基磺酰基烷基，在苯环上可选地带有烷氧基取代基，苯基硫基烷基，苯基磺酰基烷基，在苯环上可选地带有卤素或烷氧基取代基，苯氧基烷基，在苯环上可选地带有卤素或烷氧基取代基，吡啶基烷基，在吡啶环上可选地带有卤素或烷氧基取代基，噻吩基烷基，苯甲酰基烷基，苯胺基硫代羰基，苯甲酰基，吡啶基，苯基烯基，或--A--NR.sup.4 R.sup.5（其中R.sup.4和R.sup.5分别为烷基或苯基，苯环上可选地带有卤素或烷氧基取代基，A为可用O中断的烷基），及其盐，以及用于预防和治疗心脏疾病的新型羧基苯基吡啶衍生物和制药组合物。
• Method of treating congestive heart failure using carbostyril derivatives
  申请人：Otsuka Pharmaceutical Company Ltd.

  公开号：US05266577A1

  公开（公告）日：1993-11-30

  Method for the treatment of congestive heart failure or paroxymal frequent heart pulse using a carbostyril derivative of formula: ##STR1## wherein R.sup.1 is H or CN, and R.sup.2 and R.sup.3 are each H, alkyl optionally substituted by OH, cycloalkyl, alkenyl, phenyl, phenylalkyl having optionally substituents of alkoxyalkoxy, halogen, alkoxy, NO.sub.2, alkyl, CN, alkylthio or alkylsulfinyl on phenyl ring and having optionally OH-substituent on alkyl moiety, phenylsulfonylalkyl having optionally alkoxy substituent on phenyl ring, phenylthioalkyl, phenylsulfinylalkyl having optionally substituents of halogen or alkoxy on phenyl ring, phenoxyalkyl having optionally substituents of halogen or alkoxy on phenyl ring, pyridylalkyl having optionally substituents of halogen or alkoxy on pyridine ring, thienylalkyl, benzoylalkyl, anilinothiocarbonyl, benzoyl, pyridyl, phenylalkenyl, or group of -A-NR.sup.4 R.sup.5 (R.sup.4 and R.sup.5 are each alkyl or phenyl having optionally substituents of halogen or alkoxy on phenyl ring, and A is alkylene which may be interrupted with O), and a salt thereof, and novel carbostyril derivatives, and pharmaceutical composition for prophylaxis and treatment of heart diseases containing said novel carbostyril derivative.

  使用公式式的carbostyril衍生物治疗充血性心力衰竭或阵发性频繁心跳的方法，其中公式为：##STR1##其中R.sup.1为H或CN，R.sup.2和R.sup.3分别为H，烷基，可选地被OH取代的环烷基，烯基，苯基，苯基烷基，其在苯环上具有可选的alkoxyalkoxy，卤素，alkoxy，NO.sub.2，烷基，CN，alkylthio或alkylsulfinyl取代基，并在烷基部分上具有可选的OH取代基，苯基磺酰基烷基，在苯环上具有可选的alkoxy取代基，苯基硫代烷基，苯基亚砜基烷基，在苯环上具有可选的卤素或alkoxy取代基，苯氧基烷基，在苯环上具有可选的卤素或alkoxy取代基，吡啶基烷基，在吡啶环上具有可选的卤素或alkoxy取代基，噻吩基烷基，苯甲酰基烷基，苯胺基硫代羰基，苯甲酰基，吡啶基，苯基烯基，或-A-NR.sup.4 R.sup.5（其中R.sup.4和R.sup.5分别为烷基或苯基，在苯环上具有可选的卤素或alkoxy取代基，A为可以被O中断的烷基），以及其盐，以及用于预防和治疗心脏疾病的新型carbostyril衍生物和制药组合物。
• NMDA Receptor Antagonists for Neuroprotection
  申请人：Liotta Dennis C.

  公开号：US20090253710A1

  公开（公告）日：2009-10-08

  Provided are compounds, pharmaceutical compositions and methods of treatment or prophylaxis of disorders associated with NMDA receptor activity, including neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds are of the general Formula I, or a pharmaceutically acceptable salt, ester, prodrug or derivative thereof are provided: wherein: each (L) k -Ar 1 is a substituted or unsubstituted, mono or bicyclic aryl or heteroaryl; W is a bond, alkyl, or alkenyl; X is a bond, NR 1 or O and each R 1 and R 2 is independently H, alkyl, alkenyl or aralkyl or R 1 and R 2 taken together form a 5-8 membered ring; R 3− R 6 are selected from certain specific substituents or a carbonyl; Y is a bond, O, S, SO, SO 2 , CH 2 , NH, N(alkyl), or NHC(═O); and Z is OH, NR 6 R 7 , NR 8 SO 2 (alkyl), NR 8 C(O)NR 6 R 7 , NR 8 C(O)O(alkyl), NR 8 -dihydrothiazole, or NR 8 -dihydroimidazole or wherein Z can fuse with Ar 2 to form selected heterocycles.

  提供了与NMDA受体活性相关的疾病治疗或预防的化合物、制药组合物和方法，包括神经病理性疼痛、中风、创伤性脑损伤、癫痫和相关的神经事件或神经退行性疾病。提供了通式I的化合物或其药学上可接受的盐、酯、前药或衍生物: 其中：每个（L）k-Ar1是取代或未取代的、单环或双环芳基或杂环芳基；W是键、烷基或烯基；X是键、NR1或O，每个R1和R2是独立的H、烷基、烯基或芳基烷基，或R1和R2共同形成5-8成员环；R3-R6选自特定的取代基或羰基；Y是键、O、S、SO、SO2、CH2、NH、N（烷基）或NHC（═O）；Z是OH、NR6R7、NR8SO2（烷基）、NR8C（O）NR6R7、NR8C（O）O（烷基）、NR8-二氢噻唑或NR8-二氢咪唑，或Z可以与Ar2融合形成选择的杂环。
• Novel Carvedilol Analogues That Suppress Store-Overload-Induced Ca²⁺ Release
  作者：Chris D. Smith、Aixia Wang、Kannan Vembaiyan、Jingqun Zhang、Cuihong Xie、Qiang Zhou、Guogen Wu、S. R. Wayne Chen、Thomas G. Back

  DOI：10.1021/jm401090a

  日期：2013.11.14

  Carvedilol is a uniquely effective drug for the treatment of cardiac arrhythmias in patients with heart failure. This activity is in part because of its ability to inhibit store-overload-induced calcium release (SOICR) through the RyR2 channel. We describe the synthesis, characterization, and bioassay of ca. 100 compounds based on the carvedilol motif to identify features that correlate with and optimize SOICR inhibition. A single-cell bioassay was employed on the basis of the RyR2-R4496C mutant HEK-293 cell line in which calcium release from the endoplasmic reticulum through the defective channel was measured. IC50 values for SOICR inhibition were thus obtained. The compounds investigated contained modifications to the three principal subunits of carvedilol, including the carbazole and catechol moieties, as well as the linker chain containing the beta-amino alcohol functionality. The SAR results indicate that significant alterations are tolerated in each of the three subunits.
• Novel positive inotropic agents: synthesis and biological activities of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinone derivatives
  作者：Takafumi Fujioka、Shuji Teramoto、Toyoki Mori、Tetsumi Hosokawa、Takumi Sumida、Michiaki Tominaga、Youichi Yabuuchi

  DOI：10.1021/jm00098a003

  日期：1992.10

  A series of 6-(3-amino-2-hydroxypropoxy)-2(1H)-quinolinones has been synthesized and evaluated for positive inotropic activity on the canine heart. Some of these derivatives have a potent activity with none or negative chronotropic effect in isolated, blood-perfused dog heart preparations. They also display a high selectivity for positive inotropic effect over chronotropic and vasodilatory effects in anesthetized dogs. (+/-)-6-[2-Hydroxy-3-[(3-methoxybenzyl)amino]propoxy]-2(1H)-quinolinone (39) and (+/-)-6-[3-(3,4-dimethoxybenzyl)amino]-2-hydroxypropoxy]-2(1H)-quinolinone (40) were further investigated in conscious dogs. After iv administration, they did not affect heart rate or mean blood pressure at the dose producing a 50% increase in the peak of the first derivative of the left ventricular pressure. The compounds (39,OPC-18750, and 40,OPC-18790) are the most promising agents with desirable biological activities, and now are currently undergoing clinical evaluation.