Devesa Isabel, Alcaraz M José, Riguera Ricardo, Ferrándiz M Luisa
Departamento de Farmacología, Universidad de Valencia, 46100 Burjasot, Valencia, Spain.
Eur J Pharmacol. 2004 Mar 19;488(1-3):225-30. doi: 10.1016/j.ejphar.2004.02.015.
In a previous study, we reported a new pyrazolo pyrimidine derivative, N(4)-benzyl-N(6),N(6)-dimethyl-1-1(tert-butyl)-1H-pyrazolo[3,4-d]pyrimidine-6,4-diamine (DPP), which inhibited potently cyclooxygenase-2 activity in intact cell assays with minor activity against cyclooxygenase-1 (IC(50)=0.9 nM for cyclooxygenase-2 versus IC(50)=59.6 nM for cyclooxygenase-1). In the present work, this behaviour was confirmed in vivo by using the 24-h zymosan-injected mouse air pouch model (ID(50)=1.36 nM/pouch for prostaglandin E(2) level). We also studied the possible beneficial effect of DPP in the angiogenesis-dependent murine air pouch granuloma and rat paw carrageenan-induced hyperalgesia models. DPP exerted analgesic and anti-angiogenic (52% reduction in angiogenesis at 10 mg/kg, i.p.) effects that may be associated with inhibition of cyclooxygenase-2 activity.
在之前的一项研究中，我们报道了一种新的吡唑并嘧啶衍生物，N(4)-苄基-N(6),N(6)-二甲基-1-(叔丁基)-1H-吡唑并[3,4-d]嘧啶-6,4-二胺（DPP），在完整细胞试验中，它能有效抑制环氧合酶-2的活性，而对环氧合酶-1的活性较弱（环氧合酶-2的IC(50)=0.9 nM，环氧合酶-1的IC(50)=59.6 nM）。在本研究中，通过使用注射酵母聚糖24小时的小鼠气袋模型（前列腺素E(2)水平的ID(50)=1.36 nM/气袋）在体内证实了这种特性。我们还研究了DPP在依赖血管生成的小鼠气袋肉芽肿和大鼠足角叉菜胶诱导的痛觉过敏模型中可能的有益作用。DPP发挥了镇痛和抗血管生成作用（腹腔注射10 mg/kg时血管生成减少52%），这些作用可能与抑制环氧合酶-2的活性有关。
