61466-34-0Relevant academic research and scientific papers
New polycyclic pyrimidine derivatives with antiplatelet in vitro activity: Synthesis and pharmacological screening
Bruno, Olga,Schenone, Silvia,Ranise, Angelo,Bondavalli, Francesco,Barocelli, Elisabetta,Ballabeni, Vigilio,Chiavarini, Milena,Bertoni, Simona,Tognolini, Massimiliano,Impicciatore, Mariannina
, p. 629 - 636 (2007/10/03)
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-TXA2 dependent mechanisms are involved in its biological activity. Orally administered at 100mgkg-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[4,3-d]pyrimidine 4d fulfils the chemical requirements to exhibit antiplatelet activity associated with gastroprotective effect. Copyright
