SYNTHESIS, ANTIINFLAMMATORY ACTIVITY AND PLATELET ANTIAGGREGATING ACTIVITY OF A NEW SERIES OF BETA-AMINOXYPROPIONIC ACIDS

A series of beta-aminoxypropionic acids (AOPAs) had previously been de signed and synthesised as analogues of antiinflammatory arylacetic aci ds (ArAAs) in which the Ar portion is substituted by the (methyleneami noxy) methyl moiety (C = NOCH2, MAOMM). Most of these AOPAs had exhibi ted a significant antiinflammatory and antiaggregating activity. This paper reports the synthesis of a new series of beta-aminoxypropionic a cids (SAOPAs) which include the saturated (methylaminoxy)methyl moiety (CHNH-OCH2, SMAOMM) in the place of the MAOMM present in AOPAs. The a ntiinflammatory activity of SAOPAs was evaluated by the carrageenan-in duced paw edema method and the antiaggregating activity was evaluated by means of tests using arachidonic acid (AA) and adenosine diphosphat e (ADP) as the aggregating agents. Two SAOPAs were evaluated for their capacity to inhibit the cyclooxygenase enzyme by measuring the malond ialdehyde (MDA) produced by incubation of sodium arachidonate with pla telet-rich plasma (PRP). The pharmacological results showed that the s aturation of the iminic double bond led to a reduction or even the dis appearance of the antiaggreganting activity, whereas it did not induce any evident changes in the antiinflammatory activity. Theoretical stu dies were carried out in order to compare the conformation and the mol ecular reactivity of SAOPAs with those of AOPAs.