SYNTHESIS AND STUDY OF THE ANTIINFLAMMATORY PROPERTIES OF SOME PYRAZOLO[1,5-A]PYRIMIDINE DERIVATIVES

A series of pyrazolo[1,5-a]pyrimidin-7-ones (1c-17c) were synthesized to evaluate in vivo and in vitro effects induced by structural modific ations at the 2 position of ro-4-ethyl-2-phenylpyra-zolo[1,5-a]pyrimid in-7-one (FPP028). This substance, which has been previously studied, is a weak inhibitor of prostaglandin biosynthesis and a nonacid analge sic and anti-inflammatory agent devoid of ulcerogenic properties. To g ain more insight into the mechanism of action of this class of compoun ds, several in vivo tests were carried out, such as carrageenan-induce d rat paw edema and pleurisy. In vitro tests include some studies of l eukocyte functions, such as superoxide production and myeloperoxidase release. In vitro effects on arachidonic acid-, adenosine 5'-diphospha te-, and platelet-activating factor-induced platelet aggregation were also studied. Different anti-inflammatory activities were observed, de pending on the nature of substituents at the 2 position; these differe nces are probably linked to the capacity of these compounds to inhibit leukotrienes and/or prostaglandin biosynthesis with different selecti vity. 4-ethyl-2(2-thienyl)pyrazolo[1,5-a]pyrimidin-7-one (7c) proved t o be the most interesting compound of the novel synthesized series, sh owing powerful pharmacological activity in vivo as well as in vitro, t ogether with very weak acute toxicity.