3-Methylsulfanyl-10-pyrrolidin-1-yl-10H-9-oxa-2,4-diaza-phenanthrene; hydrochloride

• 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-Methylsulfanyl-10-pyrrolidin-1-yl-10H-9-oxa-2,4-diaza-phenanthrene; hydrochloride
• 英文别名: 2-methylsulfanyl-5-pyrrolidin-1-yl-5H-chromeno[4,3-d]pyrimidine;hydrochloride
• 化学式: C₁₆H₁₇N₃OS*ClH
• 分子量: 335.857
• InChiKey: DKTKMTOOOHRBJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.77
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-Methylsulfanyl-10-pyrrolidin-1-yl-10H-9-oxa-2,4-diaza-phenanthrene; hydrochloride 以 乙醇 为溶剂， 生成 10-Ethoxy-3-methylsulfanyl-10H-9-oxa-2,4-diaza-phenanthrene
  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

• 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.