Comparison of in vitro and ex vivo antiplatelet effects of 1,2-benzisothiazolin-3-one and its 2-amino derivative

The in vitro and ex vivo antiplatelet effects of 2-amino-1,2-benzisothiazol in-3-one (1) are compared with those of its parent compound 1,2-benzisothia zolin-3-one (2) and with acetylsalicylic acid (ASA) against different agoni sts. 2-Amino-1,2-benzisothiazolin-3-one inhibits adenosine diphosphate (ADP )-, arachidonic acid (AA)- and collagen-induced human platelet aggregation in vitro, with IC50 values of 8.90 x 10(-5), 1.50 x 10(-6) and 5.11 x 10(-8 ) mol/l, respectively. The strong inhibitory activity is significant not on ly for collagen but also for AA-induced aggregation. The same compound inhi bits ex vivo collagen- and particularly AA-induced rabbit platelet aggregat ion at the tested dose of 10 mg/kg i.m. In view of the potential use of 2-a mino-1,2-benzisothiazolin-3-one as antithrombotic agent, the log P values f or both 1,2-benzisothiazolin-3-one derivatives 1 and 2 are determined, to g ain an understanding of the significance of the 2-amino group in the 1,2-be nzisothiazolin-3-one moiety with respect to the biological activity under s tudy.