6-(3-氯丙氧基)-1H-喹啉-2-酮 | 63309-44-4

• 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: 6-(3-氯丙氧基)-1H-喹啉-2-酮
• 英文名称: 6-(3-chloropropoxy)quinolin-2(1H)-one
• 英文别名: 6-(3-chloropropoxy)carbostyril；6-(3-chloropropoxy)-1H-quinolin-2-one
• CAS: 63309-44-4
• 化学式: C₁₂H₁₂ClNO₂
• 分子量: 237.686
• InChiKey: DFQTUHQFWNUAKJ-UHFFFAOYSA-N

物化性质

• 熔点：
  201-202 °C(Solv: ethanol (64-17-5))
• 沸点：
  465.3±45.0 °C(Predicted)
• 密度：
  1.247±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-(3-氯丙氧基)-1H-喹啉-2-酮 在 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-Cyclohexyl-3-ethyl-1-methyl-3-[3-(2-oxo-1,2-dihydro-quinolin-6-yloxy)-propyl]-urea
  参考文献：
  名称：

  2(1H)-Quinolinone derivatives as novel anti-arteriostenotic agents showing anti-thrombotic and anti-hyperplastic activities

  摘要：

  In order to search for anti-arteriostenotic agents, a series of 2(1H)-quinolinone derivatives was synthesized and evaluated for anti-thrombotic activity and for anti-hyperplastic activity. From this series, (-)-6-[3-[3-cyclopropyl-3-[(1R,2R)-2-hydroxycyclohexyl]ureido] propoxy]-2(1H)-quinolinone (1p, OPC-33509) was selected as the best candidate by balancing the efficacy on anti-thrombosis and anti-hyperplasia. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00246-7
• 作为产物：
  描述：

  6-羟基-2(1H)-喹啉酮 、 1-溴-3-氯丙烷 在 potassium carbonate 作用下， 以 异丙醇 为溶剂， 反应 24.0h， 以63%的产率得到6-(3-氯丙氧基)-1H-喹啉-2-酮
  参考文献：
  名称：

  作为脂肪酸酰胺水解酶和胆碱酯酶抑制剂的新型氨基甲酸酯的设计和合成：分子动力学、体外和体内研究

  摘要：

  作为花生四烯酸 ( N-花生四烯酰乙醇胺 (AEA) 显示出神经保护作用，抑制其降解酶脂肪酸酰胺水解酶 (FAAH) 被认为是治疗神经退行性疾病如阿尔茨海默病 (AD) 的有希望的途径。由于基底前脑中垂死的胆碱能神经元，记忆力减退、认知障碍和胆碱能张力减弱是 AD 患者的常见标志。通过利用胆碱酯酶抑制剂 (ChEI)，乙酰胆碱 (ACh) 的降解减少，导致上述区域的胆碱能神经传递增强，最终改善 AD 患者的临床状况。在这项工作中，新的氨基甲酸酯被设计为 FAAH 和胆碱酯酶 (ChEs)（乙酰胆碱酯酶 (AChE)、丁酰胆碱酯酶 (BuChE)) 的灵感来自天然底物的结构、活性位点的结构和这些酶的众所周知的抑制剂的 SAR。所有设计的化合物都是使用不同的反应合成的。分别采用Cayman 试剂盒和Elman 方法测试了所有目标化合物对FAAH 和ChEs 的抑制活性。通常，具有氨基甲基苯基接

  DOI：

  10.1016/j.bioorg.2021.104684

文献信息

• Carbostyril derivatives
  申请人：D. Western Therapeutics Institiute

  公开号：US06143763A1

  公开（公告）日：2000-11-07

  A carbostyril derivative of the formula (1): ##STR1## wherein A is lower alkylene, R is H, halogen or lower alkoxy, R.sup.1 and R.sup.2 are each lower alkyl being optionally substituted by OH, lower alkoxy, phenyl-lower alkoxy or lower alkanoyloxy; cycloalkyl being optionally substituted by OH, hydroxy-lower alkoxy or lower alkanoyloxy; or amino being optionally substituted by lower alkyl or cycloalkyl, R.sup.3 is H, lower alkyl, lower alkenyl or hydroxy-lower alkyl, and the bond between 3- and 4-positions of the carbostyril nucleus is single or double, provided that when R and R.sup.3 are H, R.sup.1 and R.sup.2 should not be either unsubstituted lower alkyl or unsubstituted cycloalkyl, or a salt thereof, which shows antithrombotic activities, intima thickening inhibitory activity, the platelet mass dissociating activity and increasing activity of the blood flow in the brain and the peripheral vessel, and hence, is useful as medicines in the prophylaxis or treatment of various ischemic diseases.

  一种公式（1）的羟基喹啉衍生物：##STR1## 其中A是较低的烷基，R是H、卤素或较低的烷氧基，R.sup.1和R.sup.2分别是较低的烷基，可选择地被OH、较低的烷氧基、苯基-较低的烷氧基或较低的烷酰氧基取代；环烷基，可选择地被OH、羟基-较低的烷氧基或较低的烷酰氧基取代；或氨基，可选择地被较低的烷基或环烷基取代，R.sup.3是H、较低的烷基、较低的烯基或羟基-较低的烷基，且羟基喹啉核的3-和4-位置之间的键是单键或双键，前提是当R和R.sup.3是H时，R.sup.1和R.sup.2不应是未取代的较低烷基或未取代的环烷基，或其盐，具有抗血栓活性、内膜增厚抑制活性、血小板质量分离活性和增加脑部和外周血管血流活性的药物，因此，在各种缺血性疾病的预防或治疗中有用。
• Studies on 2(1H)-quinolinone derivatives as neuroleptic agents. I. Synthesis and biological activities of (4-phenyl-1-piperazinyl)-propoxy-2(1H)-quinolinone derivatives.
  作者：KAZUO BANNO、TAKAFUMI FUJIOKA、TETSURO KIKUCHI、YASUO OSHIRO、TAKASHI HIYAMA、KAZUYUKI NAKAGAWA

  DOI：10.1248/cpb.36.4377

  日期：——

  With the aim of developing a novel neuroleptic drug, a series of ω-(4-phenyl-1-piperazinyl)-alkoxy-2 (1H)-quinolinone derivatives have been synthesized and tested for anti-methamphetamine and anti-epinephrine activities. Most of the derivatives were found to possess a potent antimethamphetamine activity in the jumping behavior test on mice treated with 3-(3, 4-dihydroxyphenyl)-L-alanine (L-DOPA) and methamphetamine, or in the lethality test with methamphetamine-treated mice. They also showed relatively high anti-epinephrine potency depending on the nature or number of substituents on the phenyl group in the 4-phenyl-1-piperazinyl moiety; some of these compounds induced only weak catalepsy in mice. Among them, 7-3-[4-(2, 3-dimethylphenyl)-1-piperazinyl]propoxy}-2 (1H)-quinolinone (OPC-4392), which was suggested to be a dopamine autoreceptor agonist, was selected for further investigations. The structure-activity relationships are also discussed.

  为了开发一种新型的神经安定药物，合成了一系列ω-(4-苯基-1-哌嗪基)-烷氧基-2(1H)-喹啉酮衍生物，并测试了它们的抗甲基苯丙胺和抗肾上腺素活性。大多数衍生物在3-(3, 4-二羟基苯基)-L-天冬氨酸（L-DOPA）和甲基苯丙胺处理的小鼠的跳跃行为测试中显示出强效的抗甲基苯丙胺活性，或者在甲基苯丙胺处理的小鼠的致死性测试中表现出显著效果。它们还表现出相对较高的抗肾上腺素效能，这取决于取代基在4-苯基-1-哌嗪基上的性质或数量；其中一些化合物在小鼠中仅引起轻微的强直症。在这些化合物中，7-3-[4-(2, 3-二甲基苯基)-1-哌嗪基]丙氧基}-2(1H)-喹啉酮（OPC-4392），被认为是一种多巴胺自受体激动剂，已被选定用于进一步研究。同时，本文也讨论了结构-活性关系。
• 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。
• An efficient synthesis of optically active metabolites of platelet adhesion inhibitor OPC-29030 by lipase-catalyzed enantioselective transesterification
  作者：Kazuyoshi Kitano、Jun Matsubara、Tadaaki Ohtani、Kenji Otsubo、Yoshikazu Kawano、Seiji Morita、Minoru Uchida

  DOI：10.1016/s0040-4039(99)00946-6

  日期：1999.7

  The optically active metabolites of (S)-3,4-dihydro-6-[3-(1-o-tolyl-2-imidazolyl)sulfinyl-propoxy]-2(1H)-quinolinone (OPC-29030, 1), which is a new anti-platelet agent (platelet adhesion inhibitor), were effectively synthesized by the enzyme-catalyzed enantioselective transesterification of the racemic sulfinyl metabolites. The enzymes can recognize a stereogenic sulfur atom remote from the reaction

  的光学活性的代谢物（小号）-3,4-二氢-6- [3-（1- ö甲苯基- 2-咪唑基）亚磺酰基丙氧基] -2（1 H ^） -喹啉酮（OPC-29030，1） ，是一种新型的抗血小板药物（血小板粘附抑制剂），是通过酶催化的外消旋亚磺酰基代谢物的对映选择性酯交换反应而有效合成的。这些酶可以识别远离反应位点的立体硫原子。
• DIAMINE DERIVATIVES AND PHARMACEUTICAL CONTAINING THE SAME
  申请人：Kowa Co., Ltd.

  公开号：EP0957100A1

  公开（公告）日：1999-11-17

  This invention relates to a diamine derivative represented by the following formula (1) or a salt thereof. wherein R1 represents H, OH, an aralkyloxy group or a halogen atom; R2 represents H or a lower alkyl group; A represents -C(R3)=CH-, -CH=N-, -N(R4)-, R3 being H or OH, R4 being a lower alkyl group or an alkoxyalkyl group, -O-, or -S-; B represents a single bond, -C(R5)(R6)-(CH2)k-, R5 and R6 being H or a lower alkyl group, and k being a value of from 0 to 2, -S(O)qCH(R7), or -CH=CH-; E represents a single bond or -(CH2)3-; W and Y individually represent -CH2- or -CO-; Z represents O or S; and m is a value of 2 or 3, and n is a value of from 1 to 4; with the proviso that E is -(CH2)3- when B is a single bond and E is a single bond when B is a group other than a single bond. The diamine derivatives or salts thereof have both antileukotrienic action and antihistaminic action and are low in brain penetration, and are hence useful as asthma preventives and curatives.

  本发明涉及下式(1)所代表的二胺衍生物或其盐。 其中 R1 代表 H、OH、烷氧基或卤原子；R2 代表 H 或低级烷基；A 代表 -C(R3)=CH-、-CH=N-、-N(R4)-，R3 为 H 或 OH，R4 为低级烷基或烷氧基烷基、-O- 或 -S-；B 代表单键、-C(R5)(R6)-(CH2)k-，R5 和 R6 为 H 或低级烷基，k 的值为 0 至 2、-S(O)qCH(R7) 或 -CH=CH-；E代表单键或-(CH2)3-；W和Y分别代表-CH2-或-CO-；Z代表O或S；m的值为2或3，n的值为1至4；但当B为单键时，E为-(CH2)3-，当B为单键以外的基团时，E为单键。二胺衍生物或其盐类具有抗白三烯作用和抗组胺作用，对大脑的渗透性低，因此可作为哮喘的预防和治疗药物。