Synthesis and pharmacological evaluation of 2,5-cycloamino-5H-[1]benzopyrano[4,3-d]pyrimidines endowed with in vitro antiplatelet activity.
A series of new 2,5-cycloamino-5H-[1]benzopyrano[4,3-d]pyrimidines 3a-i have been synthesized and tested in vivo for the anti-inflammatory/analgesic/antipyretic effects and in vitro to evaluate the antiplatelet activity on guinea-pig platelet-rich plasma aggregated by collagen, adenosine-5'-diphosphate (ADP) and arachidonic acid (AA). Title compounds were ineffective in vivo; however, the pyrrolidino derivatives 3a and 3c exhibited an antiplatelet activity against all the aggregants differing from that of acetylsalicylic acid (ASA) while the 5-morpholino derivatives 3g-i showed the most potent ASA-like antiplatelet activity.
Bruno
O
O
Dipartimento di Scienze Farmaceutiche, Università degli Studi, Viale Benedetto XV, 3-16132, Genova, Italy. obruno@unige.it
Brullo
C
C
Ranise
A
A
Schenone
S
S
Bondavalli
F
F
Barocelli
E
E
Ballabeni
V
V
Chiavarini
M
M
Tognolini
M
M
Impicciatore
M
M
D000244:Adenosine Diphosphate / Q000378:metabolism; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000378:metabolism; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy; D006168:Guinea Pigs; D010146:Pain / Q000188:drug therapy; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D001578:Benzopyrans; D010975:Platelet Aggregation Inhibitors; D011743:Pyrimidines; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen