Lombardino J G, Otterness I G
J Med Chem. 1981 Jul;24(7):830-4. doi: 10.1021/jm00139a012.
A unique class of immunosuppressive agents has been found be the use of a mouse model of immunity. A number of bensothiopyrano[4,3-c]pyrazol-3-ones are potent inhibitors of both the humoral and cellular immune response developed in mice in response to El4 tumor cells. These compounds exhibit a selectivity for inhibiting the humoral response. Structure-activity relationships and Hansch analyses of data from the mouse model are discussed. One of the most potent compounds, 2-(4'-chlorophenyl)bensothiopyrano[4,3-c]pyrazol-3-one (1, CP-17 193), exhibits ED50 values for inhibiting the humoral and cellular responses in the range of 0.5-2 mg/kg, po, in the mouse model and also inhibits antibody production to several other antigens and prolongs skin graft survival in mice. These compounds are shown in several ways to be distinct from the lymphocytotoxic drugs cyclophosphamide and azathioprine.
通过使用免疫小鼠模型，发现了一类独特的免疫抑制剂。许多苯并噻喃并[4,3-c]吡唑-3-酮是小鼠针对El4肿瘤细胞产生的体液免疫和细胞免疫反应的有效抑制剂。这些化合物对抑制体液免疫反应具有选择性。讨论了来自小鼠模型的数据的构效关系和Hansch分析。其中一种最有效的化合物，2-(4'-氯苯基)苯并噻喃并[4,3-c]吡唑-3-酮(1, CP-17 193)，在小鼠模型中口服抑制体液和细胞免疫反应的ED50值在0.5-2 mg/kg范围内，还抑制对其他几种抗原的抗体产生，并延长小鼠皮肤移植的存活时间。这些化合物在几个方面显示出与淋巴细胞毒性药物环磷酰胺和硫唑嘌呤不同。
