Synthesis and pharmacological screening of novel non-acidic gastroprotective antipyretic anti-inflammatory agents with anti-platelet properties. 5-Alkyl/cycloalkylamino substituted 2-amino-5H-[1]benzopyrano[4,3-d] pyrimidines.
The preparation and screening of antipyretic, anti-inflammatory, analgesic, gastroprotective and antiplatelet activities of original non-acidic aminobenzo-pyranopyrimidine derivatives are described. Major and dose-dependent analgesic and antipyretic properties were detected in all the compounds after oral administration (6.25-100 mg kg-1) in the mouse writhing test and in the E. coli lipopolysaccharide-induced fever in the rat, respectively. Unlike the reference drug indometacin (ED50 ulcer = 9.1 mg kg-1), no gastrolesivity was displayed by all the new compounds up to 150 mg kg-1 so that therapeutical indices equal or higher than that of indometacin were calculated. Furthermore, at 100 mg kg-1 they were able to prevent ethanol-induced gastric mucosal injury in rats. At a 1 mmol/l concentration the compounds under study were as effective as acetylsalicylic acid in inhibiting in vitro platelet aggregation induced by adenosine diphosphate.
Bruno
O
O
Dipartimento di Scienze Farmaceutiche, Università degli Studi, Genova, Italy. obruno@unige.it
Schenone
S
S
Ranise
A
A
Barocelli
E
E
Chiavarini
M
M
Ballabeni
V
V
Bertoni
S
S
D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control; D005753:Gastric Mucosa / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D001578:Benzopyrans; D008070:Lipopolysaccharides; D010975:Platelet Aggregation Inhibitors; D011743:Pyrimidines