Bernard M, Hulley E, Molenda H, Stochla K, Wrzeciono U
Pharmazie. 1986 Aug;41(8):560-2.
beta-(4-Pyrazole)acrylic acids 22-28 were prepared by the Knoevenagel reaction of malonic acid and 4-formylpyrazoles 8-14. 4-Pyrazolemethylenemalonic acids 15-21 were isolated as intermediates. The latter compounds were also synthesized by treating the 4-formylpyrazoles 8-14 with diethyl malonate followed by hydrolysis of the obtained diethyl esters 15a-21a. The effect of piperidine and pyridine on the Knoevenagel condensation was investigated. The beta-(4-pyrazole)acrylic acids 22-27, on catalytic reduction, gave the corresponding beta-(4-pyrazole)propionic acids 29-34. Compounds 23, 24, 27, 29-31 and 34 appeared to be less active than phenylbutazone in carrageenin-induced oedema test, but they were less toxic than the reference drug.
通过丙二酸与4-甲酰基吡唑8-14的克诺文纳格尔反应制备了β-(4-吡唑基)丙烯酸22-28。分离得到4-吡唑基亚甲基丙二酸15-21作为中间体。后者化合物也可通过用丙二酸二乙酯处理4-甲酰基吡唑8-14,然后水解得到的二乙酯15a-21a来合成。研究了哌啶和吡啶对克诺文纳格尔缩合反应的影响。β-(4-吡唑基)丙烯酸22-27经催化还原得到相应的β-(4-吡唑基)丙酸29-34。在角叉菜胶诱导的水肿试验中,化合物23、24、27、29-31和34的活性似乎低于保泰松,但它们的毒性低于参比药物。