2-methylthio-5-hydroxy-5H-[1]benzopyrano[4,3-d]pyrimidine | 61466-34-0

• 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: 2-methylthio-5-hydroxy-5H-[1]benzopyrano[4,3-d]pyrimidine
• 英文别名: 5-hydroxy-2-methylthio-5H-[1]benzopyrano[4,3-d]pyrimidine；2-methylsulfanyl-5H-chromeno[4,3-d]pyrimidin-5-ol；2-(Methylsulfanyl)-5H-[1]benzopyrano[4,3-d]pyrimidin-5-ol；2-methylsulfanyl-5H-chromeno[4,3-d]pyrimidin-5-ol
• CAS: 61466-34-0
• 化学式: C₁₂H₁₀N₂O₂S
• 分子量: 246.29
• InChiKey: FHESHQCBBSYKPE-UHFFFAOYSA-N

物化性质

• 熔点：
  196-198 °C(Solv: ethanol (64-17-5))
• 沸点：
  505.9±45.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  80.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-methylthio-5-hydroxy-5H-[1]benzopyrano[4,3-d]pyrimidine 在 sodium hydroxide 、 potassium permanganate 作用下， 反应 0.5h， 生成 2-methylthio-5H-[1]benzopyrano[4,3-d]pyrimidin-5-one
  参考文献：
  名称：

  Petersen,U.; Heitzer,H., Justus Liebigs Annalen der Chemie, 1976, p. 1663 - 1673

  摘要：

  DOI：
• 作为产物：
  描述：

  S-甲基异硫脲硫酸盐 、 色酮-3-甲醛 在 sodium hydroxide 、 三乙胺 作用下， 反应 3.0h， 以87%的产率得到2-methylthio-5-hydroxy-5H-[1]benzopyrano[4,3-d]pyrimidine
  参考文献：
  名称：

  New polycyclic pyrimidine derivatives with antiplatelet in vitro activity: synthesis and pharmacological screening

  摘要：

  The preparation and the pharmacological screening of novel anti-aggregatory/antiphlogistic polycyclic pyrimidine derivatives are described. The compounds were developed starting from bioactive 2-aminobenzopyranopyrimidine derivatives in order to assess the importance of the benzopyrano[4,3-d]pyrimidine structure and the role of an amino basic moiety in position 2. Antiplatelet activity was assessed in vitro against ADP and arachidonic acid-induced aggregation in guinea-pig plasma. Anti-inflammatory analgesic/antipyretic activities were studied in rat paw oedema, mouse writhing test and E coli-induced rat fever. Ulcerogenic and gastroprotective effects were also investigated in vivo on rat gastric mucosa. Among the tested compounds, the 5-substituted benzopyranopyrimidine derivatives 3d and 4d proved to be the most active antiplatelet agents as potent as acetylsalicylic acid against arachidonic acid-stimulated aggregation. Furthermore the 2-methylthio derivative 4d was endowed with greater efficacy against ADP aggregation suggesting that additional non-TXA(2) dependent mechanisms are involved in its biological activity. Orally administered at 100 mg kg(-1) in rats this latter compound displayed antiphlogistic acitivity comparable to indomethacin (10 mg kg(-1)) coupled with an unusual gastroprotective effect on ethanol-induced ulcers. In conclusion, these findings indicate that the 5-pyrrolidino-2-methylthiobenzopyrano[4d] fulfils the chemical requirements to exhibit antiplatelet activity associated with gastroprotective effect. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00272-8

文献信息

• Pharmazeutische Präparate enthaltend substituierte Äther-Verbindungen, ihre Verwendung, neue substituierte Äther-Verbindungen, sowie Verfahren zu ihrer Herstellung
  申请人：CIBA-GEIGY AG

  公开号：EP0051177A2

  公开（公告）日：1982-05-12

  Die Erfindung betrifft pharmazeutische Präparate enthaltend neue substituierte Aether der Formel 1 worin Ph einen gegebenenfalls substituierten 1,2-Phenylenrest bedeutet, R für einen gegebenenfalls durch einen Ph1-Rest substituierten niederaliphatischen Kohlenwasserstoffrest, wobei Ph1 ein gegebenenfalls substituierter Phenylrest ist, einen 3 bis 7 Kohlenstoffatome enthaltenden Cycloalkylrest, einen durch einen heterocyclischen Rest aromatischen Charakters substituierten Niederalkylrest oder einen Rest der Formel (CH2CH2O)n-CH2CH2OR4 steht, worin n 0, 1 oder 2 ist und R4 Wasserstoff oder Niederalkyl bedeutet, jedes der Symbole R, und R2 für Wasserstoff oder Niederalkyl steht, R3 einen gegebenenfalls substituierten Phenylrest Phi, einen gegebenenfalls durch Ph, substituierten Niederalkylrest, einen 3 bis 7 Kohlenstoffatome enthaltenden Cycloalkylrest; einen Cycloalkyl-Ph1-Rest, worin Cycloalkyl und Ph1 die oben angegebenen Bedeutungen haben, oder einen heterocyclischen Rest aromatischen Charakters bedeutet, und therapeutisch verwendbare Salze dieser Verbindungen, mit lipidsenkenden, antiarteriosklerotischen und analgetischen Wirkungen. Ebenfalls umfasst sind neue substituierte Aether der Formel I, und ihre Salze, mit Ausnahme der Verbindung der Formel I, worin Ph unsubstituiertes 1,2-Phenylen bedeutet, R für Aethyl steht, jedes der Symbole R, und R3 Methyl bedeutet, R2 für Wasserstoff steht, und ihres Perchlorats. Die neuen Verbindungen können z.B. durch Verätherung einer der Formel I entsprechenden Verbindung, worin R für Wasserstoff steht.

  本发明涉及含有式 1 的新取代醚的药物制剂。 其中 Ph 是任选取代的 1,2-亚苯基自由基，R 是任选被 Ph1 自由基取代的低级脂肪烃自由基，Ph1 是任选取代的苯基自由基、含 3 至 7 个碳原子的环烷基自由基、被芳香杂环自由基取代的低级烷基自由基或式 (CH2CH2O)n-CH2CH2OR4 的自由基。其中 n 为 0、1 或 2，R4 为氢或低级烷基，符号 R 和 R2 各为氢或低级烷基，R3 为任选取代的苯基、任选被 Ph 取代的低级烷基、含 3 至 7 个碳原子的环烷基环烷基-Ph1 基（其中环烷基和 Ph1 具有上述含义）或芳香族杂环基，以及这些化合物的治疗用盐，具有降血脂、抗动脉硬化和镇痛作用。此外，还包括式 I 的新取代醚及其盐类，但式 I 的化合物除外，其中 Ph 为未取代的 1,2-亚苯基，R 为乙基，符号 R 和 R3 均为甲基，R2 为氢，以及其高氯酸盐。新化合物可通过醚化式 I 对应的化合物（其中 R 为氢）等方法获得。
• Synthesis, antiplatelet and antithrombotic activities of new 2-substituted benzopyrano[4,3-d]pyrimidin-4-cycloamines and 4-amino/cycloamino-benzopyrano[4,3-d]pyrimidin-5-ones
  作者：Olga Bruno、Chiara Brullo、Silvia Schenone、Francesco Bondavalli、Angelo Ranise、Massimiliano Tognolini、Mariannina Impicciatore、Vigilio Ballabeni、Elisabetta Barocelli

  DOI：10.1016/j.bmc.2005.07.066

  日期：2006.1

  Atherothrombotic coronary artery disease, associated with deep vein thrombosis, is one of the most common causes of death worldwide. Recently, antiplatelet combination therapy using agents with different mechanisms of action, Such as aspirin, dipyridamole, and thienopyridines, seems to be an attractive preventive approach. Moreover, several large, randomized clinical trials support combination therapy with aspirin plus warfarin in high-risk patients with atherosclerotic heart disease. Our research on the benzopyrano[4,3-d]pyrimidine system gave rise to the synthesis of a large number of Compounds endowed with in vitro anti-aggregating activity. Several SAR considerations Suggest that the benzopyranopyrimidine system is an appropriate scaffold to obtain molecules that are able to act simultaneously in different pathways of aggregation. Now, we report the synthesis of new 2-substituted benzopyrano[4,3-d]pyrimidin-4-cycloamines and 4-amino/cycloamino-benzopyrano[4,3-d]pyrimidin-5-ones and the results of the pharmacological study on haemostasis. Some tested compounds showed a large-spectrum antiplatelet activity in vitro, and are more potent than aspirin as antithrombotics in vivo but, at variance with aspirin, they do not increase bleeding. This paper describes novel antithrombotic Compounds with an interesting pharmacological profile and a potentially attractive benefit/risk ratio, with their mechanism of action generally, but not exclusively, dependent on antiplatelet activity, deserving further investigations. (c) 2005 Elsevier Ltd. All rights reserved.
• Synthesis and pharmacological evaluation of 5H-[1]benzopyrano[4,3-d]pyrimidines effective as antiplatelet/analgesic agents
  作者：Olga Bruno、Chiara Brullo、Silvia Schenone、Francesco Bondavalli、Angelo Ranise、Massimiliano Tognolini、Vigilio Ballabeni、Elisabetta Barocelli

  DOI：10.1016/j.bmc.2003.11.018

  日期：2004.2

  Synthesis and pharmacological screening of new2-methylthio/2-methanesulfonyl/2-methoxy-5H-[1]benzopyrano[4,3-d]pyrimidines were planned in order to study the effects of the 5-substitution with alkoxy/phenoxy/alkylthio and phenylthio groups both on in vitro antiplatelet and in vivo antinociceptive activities. Antiplatelet activity was assessed in vitro against ADP, Arachidonic acid and U46619 induced aggregation, in rabbit plasma. Anti-inflammatory, analgesic and antipyretic activities were tested in rat paw edema, mouse writhing test and LPS induced rat fever, respectively. Amongst test compounds, 2-methylthio derivatives displayed an ASA-like antiplatelet activity whereas 2-methoxy and, particularly, 2-methanesulfonyl derivatives showed a broad spectrum of antiplatelet action, inhibiting both the ADP- and the AA- and U46619-induced aggregation. With regard to the in vivo pharmacological activities, mainly the 2-methoxy derivatives showed a significant analgesic effect comparable to that of indomethacin. SAR considerations, also in comparison with a number of previously described compounds, were performed. (C) 2003 Elsevier Ltd. All rights reserved.
• PETERSEN U.; HEITZER H., J. LIEBIGS ANN. CHEM. <JLAC-BF>, 1976, NO 9, 1663-1673
  作者：PETERSEN U.、 HEITZER H.

  DOI：——

  日期：——
• New polycyclic pyrimidine derivatives with antiplatelet in vitro activity: synthesis and pharmacological screening
  作者：Olga Bruno、Silvia Schenone、Angelo Ranise、Francesco Bondavalli、Elisabetta Barocelli、Vigilio Ballabeni、Milena Chiavarini、Simona Bertoni、Massimiliano Tognolini、Mariannina Impicciatore

  DOI：10.1016/s0968-0896(00)00272-8

  日期：2001.3

  The preparation and the pharmacological screening of novel anti-aggregatory/antiphlogistic polycyclic pyrimidine derivatives are described. The compounds were developed starting from bioactive 2-aminobenzopyranopyrimidine derivatives in order to assess the importance of the benzopyrano[4,3-d]pyrimidine structure and the role of an amino basic moiety in position 2. Antiplatelet activity was assessed in vitro against ADP and arachidonic acid-induced aggregation in guinea-pig plasma. Anti-inflammatory analgesic/antipyretic activities were studied in rat paw oedema, mouse writhing test and E coli-induced rat fever. Ulcerogenic and gastroprotective effects were also investigated in vivo on rat gastric mucosa. Among the tested compounds, the 5-substituted benzopyranopyrimidine derivatives 3d and 4d proved to be the most active antiplatelet agents as potent as acetylsalicylic acid against arachidonic acid-stimulated aggregation. Furthermore the 2-methylthio derivative 4d was endowed with greater efficacy against ADP aggregation suggesting that additional non-TXA(2) dependent mechanisms are involved in its biological activity. Orally administered at 100 mg kg(-1) in rats this latter compound displayed antiphlogistic acitivity comparable to indomethacin (10 mg kg(-1)) coupled with an unusual gastroprotective effect on ethanol-induced ulcers. In conclusion, these findings indicate that the 5-pyrrolidino-2-methylthiobenzopyrano[4d] fulfils the chemical requirements to exhibit antiplatelet activity associated with gastroprotective effect. (C) 2001 Elsevier Science Ltd. All rights reserved.