3-chloro-5-hydroxy-9H-xanthen-9-one | 57317-09-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 3-chloro-5-hydroxy-9H-xanthen-9-one
• 英文别名: 3-Chloro-5-hydroxyxanthone；3-chloro-5-hydroxyxanthen-9-one
• CAS: 57317-09-6
• 化学式: C₁₃H₇ClO₃
• 分子量: 246.65
• InChiKey: JLKDVXGGOVSDCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-chloro-5-hydroxy-9H-xanthen-9-one 在 sodium hydroxide 作用下， 以 丙醇 为溶剂， 生成 5-[2-hydroxy-3-(propan-2-ylamino)propoxy]-3-chloro-9H-xanthen-9-one hydrochloride
  参考文献：
  名称：

  Cardiovascular activity of the chiral xanthone derivatives

  摘要：

  A series of 6 derivatives of xanthone were synthesized and evaluated for cardiovascular activity. The following pharmacological experiments were conducted: the binding affinity for adrenoceptors, the influence on the normal electrocardiogram, the effect on the arterial blood pressure, the effect on blood pressor response and prophylactic antiarrhythmic activity in adrenaline induced model of arrhythmia (rats, iv). Two compounds revealed nanomolar affinity for alpha(1)-adrenoceptor which was correlated with the strongest cardiovascular (antiarrhythmic and hypotensive) activity in animals' models. They were enantiomers of previously described (R, S)-4-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propoxy)- 9H-xanthen-9-one hydrochloride and revealed similar antiarrhythmic potential in adrenaline induced model of arrhythmia in rats after intravenous injection (ED50 = 0.53 mg/kg and 0.81 mg/kg, respectively). These values were lower than values obtained for reference drug urapidil. These compounds were more active in this experiment than urapidil (ED50 = 1.26 mg/kg). The compound 5 administered iv at doses of 0.62-2.5 mg/kg at the peak of arrhythmia prevented and/or reduced the number of premature ventricular beats in a statistically significant manner. The ED50 value was 1.20 mg/kg. The S-enantiomer (6) given at the same doses did not show therapeutic antiarrhythmic activity in this model.These compounds significantly decreased the systolic and diastolic blood pressure throughout the whole observation period in anesthetized, normotensive rats. The studied enantiomers showed higher toxicity than urapidil, but imperceptibly higher that another cardiovascular drugs, that is, carvedilol or propranolol. They were also evaluated for mutagenic potential in the Ames (Salmonella) test. It was found that at the concentrations tested the compounds were non mutagenic when compared to solvent control.Results were quite promising and suggested that in the group of xanthone derivatives new potential antiarrhythmics and hypotensives might be found. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.09.005
• 作为产物：
  描述：

  4-Chloro-2-(2-methoxyphenoxy)benzoic acid 在 硫酸 作用下， 反应 48.0h， 生成 3-chloro-5-hydroxy-9H-xanthen-9-one
  参考文献：
  名称：

  an吨酮的一些哌嗪衍生物的合成及药理性质的初步评价

  摘要：

  合成了一系列9种黄酮的哌嗪衍生物，并评估了其心血管活性。进行了以下药理实验：肾上腺素诱发的心律失常模型（大鼠，静脉注射）对肾上腺素受体的结合亲和力，对正常心电图的影响，对动脉血压的影响和预防性抗心律不齐活性。三种化合物揭示α纳摩尔亲和力1 -肾上腺素能受体，将其用最强的心血管（抗心律失常和低血压）在动物模型活性相关。最有前途的化合物是4-（3-（4-（2-（甲氧基苯基）哌嗪-1-基）丙氧基）-9 H-黄体酮-9-盐酸盐（12），具有ED 50的抗心律失常活性。肾上腺素引起的心律不齐的心律失常值为0.69 mg / kg（大鼠，静脉注射）。其他合成的x吨酮衍生物，即（R，S）-4-（2-羟基-3-（4-（2-甲氧基苯基）哌嗪-1-基）丙氧基）-9 H-黄嘌呤-9-盐酸盐（10）和（R，S）-4-（2-乙酰氧基-3-（4-（2-甲氧基苯基）哌嗪-1-基）丙氧基）-9 H-黄嘌呤-9-盐酸盐（1

  DOI：

  10.1016/j.bmc.2012.11.014

文献信息

• Preliminary evaluation of pharmacological properties of some xanthone derivatives
  作者：Henryk Marona、Natalia Szkaradek、Anna Rapacz、Barbara Filipek、Małgorzata Dybała、Agata Siwek、Marek Cegła、Edward Szneler

  DOI：10.1016/j.bmc.2008.12.031

  日期：2009.2

  A series of xanthone derivatives were synthesized and examined for electrocardiographic, antiarrhythmic, hypotensive and anticonvulsant activities as well as for α1- and β1-adrenergic binding affinities. Among the investigated compounds, some of them exhibited significant antiarrhythmic and/or hypotensive activity. The data obtained via receptor binding assay are in agreement with pharmacological results

  一系列呫吨酮衍生物的合成和检查心电图，抗心律不齐，降血压和抗惊厥活性，以及用于α 1 -和β 1 -肾上腺素能结合亲和力。在所研究的化合物中，其中一些表现出明显的抗心律不齐和/或降压活性。通过受体结合测定获得的数据与药理学结果一致，并且可以解释新合成结构的抗心律不齐和/或降压活性。
• Synthesis and preliminary evaluation of pharmacological properties of some piperazine derivatives of xanthone
  作者：Natalia Szkaradek、Anna Rapacz、Karolina Pytka、Barbara Filipek、Agata Siwek、Marek Cegła、Henryk Marona

  DOI：10.1016/j.bmc.2012.11.014

  日期：2013.1

  erazine-1-yl)propoxy)-9H-xanthen-9-one hydrochloride (12) which revealed antiarrhythmic activity with ED50 value of 0.69 mg/kg in adrenaline induced arrhythmia (rats, iv). Other synthesized xanthone derivatives, that is, (R,S)-4-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one hydrochloride (10) and (R,S)-4-(2-acetoxy-3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one

  合成了一系列9种黄酮的哌嗪衍生物，并评估了其心血管活性。进行了以下药理实验：肾上腺素诱发的心律失常模型（大鼠，静脉注射）对肾上腺素受体的结合亲和力，对正常心电图的影响，对动脉血压的影响和预防性抗心律不齐活性。三种化合物揭示α纳摩尔亲和力1 -肾上腺素能受体，将其用最强的心血管（抗心律失常和低血压）在动物模型活性相关。最有前途的化合物是4-（3-（4-（2-（甲氧基苯基）哌嗪-1-基）丙氧基）-9 H-黄体酮-9-盐酸盐（12），具有ED 50的抗心律失常活性。肾上腺素引起的心律不齐的心律失常值为0.69 mg / kg（大鼠，静脉注射）。其他合成的x吨酮衍生物，即（R，S）-4-（2-羟基-3-（4-（2-甲氧基苯基）哌嗪-1-基）丙氧基）-9 H-黄嘌呤-9-盐酸盐（10）和（R，S）-4-（2-乙酰氧基-3-（4-（2-甲氧基苯基）哌嗪-1-基）丙氧基）-9 H-黄嘌呤-9-盐酸盐（1
• 1'-Substituted xanthene-9-spiro-4'-piperidine derivatives
  申请人：Imperial Chemical Industries Limited

  公开号：US04001419A1

  公开（公告）日：1977-01-04

  The disclosure relates to xanthene derivatives which possess analgesic activity, to processes for the manufacture of said derivatives and to pharmaceutical compositions containing them. Typical of the xanthene derivatives disclosed is 6-chloro-4-hydroxy-1'-methylxanthene-9-spiro-4'-piperidine.

  该披露涉及具有镇痛活性的黄色素衍生物，以及用于制造该衍生物的过程和含有它们的药物组合物。披露的黄色素衍生物的典型代表是6-氯-4-羟基-1'-甲基黄色素-9-螺环-4'-哌啶。
• Synthesis and preliminary anti-inflammatory evaluation of xanthone derivatives
  作者：Dorota Żelaszczyk、Anna Lipkowska、Natalia Szkaradek、Karolina Słoczyńska、Agnieszka Gunia-Krzyżak、Tadeusz Librowski、Henryk Marona

  DOI：10.1515/hc-2017-0215

  日期：2018.8.28

  Abstract Xanthone derivatives of acetic, propionic and 2-methylpropionic acids were synthesized and assayed for their anti-inflammatory, analgesic and ulcerogenic activities. Compound 8 causes a dose-dependent diminution of paw edema (up to 61%) in the carrageenan model and at the highest tested dose reduces mechanical hyperalgesia in the Randall-Selitto test more effectively than the reference compound

  摘要 合成了乙酸、丙酸和 2-甲基丙酸的呫吨酮衍生物，并测定了它们的抗炎、镇痛和致溃疡活性。化合物 8 在角叉菜胶模型中导致爪水肿的剂量依赖性减轻（高达 61%），并且在最高测试剂量下，Randall-Selitto 测试中的机械痛觉过敏比参考化合物更有效（~75% 和~32%） ， 分别）。它在大鼠肝微粒体中显示出高体外代谢稳定性（Clint=12.5 μL/mg/min，t1/2=138.6 min）。所研究的呫吨酮衍生物均无致溃疡性。本研究的结果表明，化合物 8 可能在未来用于寻找没有致溃疡作用的镇痛和抗水肿药物。
• 1'-Substituted xanthene-9-spiro-4'-piperidine derivatives and analgesic
  申请人：Imperial Chemical Industries Limited

  公开号：US04268514A1

  公开（公告）日：1981-05-19

  The disclosure relates to xanthene derivatives which possess analgesic activity, to processes for the manufacture of said derivatives and to pharmaceutical compositions containing them. Typical of the xanthene derivatives disclosed is 6-chloro-4-hydroxy-1'-methylxanthene-9-spiro-4'-piperidine.

  本公开涉及具有镇痛活性的苯并吩嗪衍生物，以及制造该衍生物的过程和含有它们的药物组合物。本公开披露的苯并吩嗪衍生物的典型代表是6-氯-4-羟基-1'-甲基苯并吩嗪-9-螺-4'-哌啶。