6-[3-(1,2,4-triazol-1-yl)propoxy]-3,4-dihydrocarbostyril | 70758-97-3

• 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-[3-(1,2,4-triazol-1-yl)propoxy]-3,4-dihydrocarbostyril
• 英文别名: 2(1H)-Quinolinone, 3,4-dihydro-6-[3-(1H-1,2,4-triazol-1-yl)propoxy]-；6-[3-(1,2,4-triazol-1-yl)propoxy]-3,4-dihydro-1H-quinolin-2-one
• CAS: 70758-97-3
• 化学式: C₁₄H₁₆N₄O₂
• 分子量: 272.307
• InChiKey: AJBVCGROXNQILZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  69
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  溴乙烷 、 6-[3-(1,2,4-triazol-1-yl)propoxy]-3,4-dihydrocarbostyril 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-ethyl-6-[3-(1,2,4-triazol-1-yl)propoxy]-3,4-dihydrocarbostyril
  参考文献：
  名称：

  Carbostyril derivatives and salts thereof and pharmaceutical composition

  摘要：

  下列一般式所示的碳基喹啉衍生物或其制药可接受的盐：##STR1## 其中Z，A，XN，R，R.sup.1和R.sup.2如规范中所定义。这些碳基喹啉衍生物在制药组合物中用于抑制血小板粘附。

  公开号：

  US05008274A1
• 作为产物：
  描述：

  1H-1,2,4-三唑 、 6-(3-bromopropoxy)-3,4-dihydro-2(1H)-quinolinone 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 异丙醇 为溶剂， 以37%的产率得到6-[3-(1,2,4-triazol-1-yl)propoxy]-3,4-dihydrocarbostyril
  参考文献：
  名称：

  Synthesis of 2(1H)-Quinolinone Derivatives and Their Inhibitory Activity on the Release of 12(S)-Hydroxyeicosatetraenoic Acid (12-HETE) from Platelets.

  摘要：

  寻找能够有效抑制12(S)-羟基二十碳四烯酸（12-HETE）释放的化合物，这种物质在多种循环系统疾病和动脉硬化的发病机制中扮演重要角色，最终引导我们发现了6-[4-(1-环己基-5-四唑基)丁氧]-3, 4-二氢-2(1H)-喹啉酮（西洛他唑）和含有唑类侧链的2(1H)-喹啉酮衍生物。合成了多种2(1H)-喹啉酮衍生物，并在体外测试了它们对人血小板的抑制活性。3, 4-二氢-6-[3-(1-邻甲基苯基咪唑-2-基)亚砜基丙氧]-2(1H)-喹啉酮（5k）是其中一种最有效的12-HETE释放抑制剂，其效能优于依斯可林。此外，亚砜化合物5k在大鼠体内表现出对血小板粘附的抑制活性。由于5k是外消旋体，因此合成了其对映体，并比较了它们在体外和体内的效能。 (S)-(+)-5k具有最佳的药理特性，并被选为进一步开发的候选药物。文中讨论了结构-活性关系。

  DOI：

  10.1248/cpb.43.1724

文献信息

• Carbostyril derivatives and salts thereof and pharmaceutical
  申请人：Otsuka Pharmaceutical Co. Ltd.

  公开号：US05434164A1

  公开（公告）日：1995-07-18

  Carbostyril derivatives and salts thereof represented by the general formula (1a), including some known compounds, possess activities for inhibiting adhesion of thrombocytes. ##STR1## Z, A, X, R, R.sup.1 and R.sup.2 are defined in the specification. Some carbostyril derivatives having chemical structural formulas similar to those of carbostyril derivatives and salts thereof represented by the general formula (1a) have been known in prior art references, however the above-mentioned pharmacological activities have not been known to the present date.

  通式（1a）所表示的羧基苯基咪唑衍生物及其盐，包括一些已知化合物，具有抑制血小板粘附活性。其中，Z、A、X、R、R.sup.1和R.sup.2在说明书中有定义。先前的文献中已知一些具有与通式（1a）所表示的羧基苯基咪唑衍生物及其盐相似的化学结构式的羧基苯基咪唑衍生物，但上述药理活性直到现在才被发现。
• Carbostyril derivatives, process for preparing them, pharmaceutical composition, and use
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：EP0240015A2

  公开（公告）日：1987-10-07

  Carbostyril derivatives and salts thereof represented by the general formula (1), including some known compounds, possess activities for inhibiting adhesion of thrombocytes. Some carbostyril derivatives having chemical structural formulas similar to those of carbostyril derivatives and salts thereof represented by the general formula (1) have been known in the prior art references, however above-mentioned pharmacological activities have not been known yet up to the date. Processes for preparing carbostyril derivatives offormu- la (1), a pharmaceutical composition containing them, or a salt thereof, as active ingredient, and their use in the preparation of a medicament for inhibiting adhesion of thrombocytes are also disclosed.

  通式(1)代表的羧基吡啶衍生物及其盐类，包括一些已知化合物，具有抑制血小板粘附的活性。 一些羧基吡啶衍生物的化学结构式与通式(1)代表的羧基吡啶衍生物及其盐类相似，在现有技术参考文献中已为人所知，但上述药理活性至今尚未为人所知。 本发明还公开了制备通式(1)代表的羧基吡啶衍生物、含有它们或其盐类作为活性成分的药物组合物的工艺，以及它们在制备抑制血小板粘附的药物中的用途。
• US5008274A
  申请人：——

  公开号：US5008274A

  公开（公告）日：1991-04-16
• US5434164A
  申请人：——

  公开号：US5434164A

  公开（公告）日：1995-07-18
• Synthesis of 2(1H)-Quinolinone Derivatives and Their Inhibitory Activity on the Release of 12(S)-Hydroxyeicosatetraenoic Acid (12-HETE) from Platelets.
  作者：Tetsuyuki UNO、Yasushi OZEKI、Yasuo KOGA、Gil-Namg CHU、Minoru OKADA、Katsumi TAMURA、Takehiro IGAWA、Fumiko UNEMI、Masaru KIDO、Takao NISHI

  DOI：10.1248/cpb.43.1724

  日期：——

  A search for potent inhibitors of release of 12(S)-hydroxyeicosatetraenoic acid (12-HETE), which plays an important role in the pathogenesis of various circulatory disorders and arteriosclerosis, led us to 6-[4-(1-cyclohexyl-5-tetrazolyl)butoxy]-3, 4-dihydro-2(1H)-quinolinone (cilostazol) and 2(1H)-quinoinone derivatives having an azole group in the side chain. Many 2(1H)-quinolilnone derivatives were synthesized and tested in vitro for the inhibitory activity in human platelets. 3, 4-Dihydro-6-[3-(1-o-tolylimidazol-2-yl)sulfinylpropoxy]-2(1H)-quinolinone (5k) was found to be one of the most potent inhibitors of 12-HETE release, being more potent than esculetin. In addition, the sulfoxide 5k showed in vivo inhibitory activity on platelet adhesion in rats. Since 5k is recemic, the enantiomers were prepared and their potencies were compared in vitro and in vivo. (S)-(+)-5k had the best pharmacological profile and was selected as a candidate drug for further development. The structure-activity relationships are discussed.

  寻找能够有效抑制12(S)-羟基二十碳四烯酸（12-HETE）释放的化合物，这种物质在多种循环系统疾病和动脉硬化的发病机制中扮演重要角色，最终引导我们发现了6-[4-(1-环己基-5-四唑基)丁氧]-3, 4-二氢-2(1H)-喹啉酮（西洛他唑）和含有唑类侧链的2(1H)-喹啉酮衍生物。合成了多种2(1H)-喹啉酮衍生物，并在体外测试了它们对人血小板的抑制活性。3, 4-二氢-6-[3-(1-邻甲基苯基咪唑-2-基)亚砜基丙氧]-2(1H)-喹啉酮（5k）是其中一种最有效的12-HETE释放抑制剂，其效能优于依斯可林。此外，亚砜化合物5k在大鼠体内表现出对血小板粘附的抑制活性。由于5k是外消旋体，因此合成了其对映体，并比较了它们在体外和体内的效能。 (S)-(+)-5k具有最佳的药理特性，并被选为进一步开发的候选药物。文中讨论了结构-活性关系。