Effects of a novel pyridylsulphonyl thiazole derivative, FR115092, on autoimmune and mitomycin C-induced thrombycytopenia in mice

Dapsone (4,4'-diaminodiphenyl sulphone), an antileprotic and antimalarial d rug, has been reported to be of therapeutic benefit in idiopathic thrombocy topenic purpura in the clinic. However, adverse reactions such as haemolyti c anaemia have often been observed. In this study, we found that dapsone in creased the number of platelets and decreased the number of red blood cells in male (NZWxBXSB)F-1 (W/BF1) mice, an animal model of idiopathic thromboc ytopenic purpura. In studies to prepare derivatives of dapsone with weaker side effects than the parent compound, FR115092 (2-[5-(2-pyridylsulphonyl)t hiazolyl] amine) was discovered. The effect of FR115092 on the number of bl ood cells was studied and compared with dapsone in mice. FR115092 increased the number of platelets without reducing the number of r ed blood cells in W/BF1 mice. This drug significantly suppressed the increa se in circulating autoantibodies against platelets and increased the number of megakaryocytes. Furthermore, FR115092 inhibited the reduction of the nu mber of platelets in mitomycin C-induced thrombocytopenic mice, as a conseq uence of its enhancement of growth and maturation of megakaryocytes. These findings suggest that FR115092 may be effective against various throm bocytopenias, without inducing haemolytic anaemia.