Effects of a novel pyridylsulphonyl thiazole derivative, FR115092, on autoimmune and mitomycin C-induced thrombocytopenia in mice.
Dapsone (4,4'-diaminodiphenyl sulphone), an antileprotic and antimalarial drug, has been reported to be of therapeutic benefit in idiopathic thrombocytopenic purpura in the clinic. However, adverse reactions such as haemolytic anaemia have often been observed. In this study, we found that dapsone increased the number of platelets and decreased the number of red blood cells in male (NZWxBXSB)F1 (W/BF1) mice, an animal model of idiopathic thrombocytopenic purpura. In studies to prepare derivatives of dapsone with weaker side effects than the parent compound, FR115092 (2-[5-(2-pyridylsulphonyl)thiazolyl]amine) was discovered. The effect of FR115092 on the number of blood cells was studied and compared with dapsone in mice. FR 115092 increased the number of platelets without reducing the number of red blood cells in W/BF1 mice. This drug significantly suppressed the increase in circulating autoantibodies against platelets and increased the number of megakaryocytes. Furthermore, FR115092 inhibited the reduction of the number of platelets in mitomycin C-induced thrombocytopenic mice, as a consequence of its enhancement of growth and maturation of megakaryocytes. These findings suggest that FR115092 may be effective against various thrombocytopenias, without inducing haemolytic anaemia.
Nishigaki
F
F
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, Osaka, Japan. fusako_nishigaki@po.fujisawa.co.jp
Tsujimoto
S
S
Inami
M
M
Matsumoto
S
S
Naoe
Y
Y
Kawamura
I
I
Manda
T
T
Shimomura
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001323:Autoantibodies / Q000097:blood / Q000187:drug effects; D015551:Autoimmunity / Q000187:drug effects*; D001792:Blood Platelets / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D003622:Dapsone / Q000494:pharmacology; D004906:Erythrocyte Count / Q000187:drug effects; D005260:Female; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D016685:Mitomycin / Q000009:adverse effects*; D010976:Platelet Count / Q000187:drug effects; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D011725:Pyridines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D013926:Thrombopoietin / Q000494:pharmacology; D013997:Time Factors
C116439:5-(2-pyridylsulfonyl)-2-thiazolamine; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001323:Autoantibodies; D011725:Pyridines; D013844:Thiazoles; D016685:Mitomycin; D003622:Dapsone; D013926:Thrombopoietin