申请人:Chandy George K.
公开号:US20070293554A1
公开(公告)日:2007-12-20
Compounds, preparations and methods for immunosuppressive treatment of autoimmune disorders, graft rejection and/or graft/host disease. Therapeutically effective amounts of certain substituted triarylmethane compounds, such as 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole, are administered to mammalian patients to selectively inhibit the calcium-activated K
+
channel (IKCa1) in lymphocytes, monocytes, macrophages, platelets or endothelial cells without concomitant inhibition of P450-dependent enzyme systems, resulting in reduction of antigen-, cytokine-, or mitogen-induced calcium entry through store operated calcium channels in these cells, suppression of cytokine production by these cells, and inhibition of activation of these cells. Such inhibition of the Ca
++
activated K
+
channel (IKCa1) prevents the pre-Ca
++
stage of cell activation and thus causes immunosuppression and an anti-inflammatory response.
化合物、制剂和方法用于免疫抑制治疗自身免疫性疾病、移植排斥和/或移植宿主病。将某些取代三芳基甲烷化合物,例如1-[(2-氯苯基)二苯甲基]-1H-吡唑酮,以治疗剂量给哺乳动物患者,以选择性抑制淋巴细胞、单核细胞、巨噬细胞、血小板或内皮细胞中的钙激活K+通道(IKCa1),而不伴随P450依赖性酶系统的抑制,从而减少这些细胞中抗原、细胞因子或诱导剂引起的钙离子进入,抑制这些细胞的细胞因子产生,并抑制这些细胞的激活。这种对Ca++激活的K+通道(IKCa1)的抑制防止了细胞激活的前Ca++阶段,从而引起免疫抑制和抗炎反应。