Daidone G, Maggio B, Plescia S, Raffa D, Schillaci D, Migliara O, Caruso A, Cutuli V M, Amico-Roxas M
Dipartimento di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Italy.
Farmaco. 1998 May 30;53(5):350-6. doi: 10.1016/s0014-827x(98)00034-2.
Several new 1-methyl-5-[substituted-4-oxo-1,2,3-benzotriazin-3-yl] -1H-pyrazole-4-acetic acids and their ethyl ester derivatives were prepared. The compounds were tested for analgesic and antiinflammatory activities, acute toxicity, ulcerogenic effect, and as in vitro inhibitors of 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), since it is claimed that the inhibition of such an enzyme predicts in vivo antiinflammatory activity. Some compounds were more active than phenylbutazone in the phenylbenzoquinone and acetic acid peritonitis tests, and equiactive to the same drug in the carrageenin paw edema test. All the compounds inhibited the 3 alpha-HSD, but no correlation was observed with the paw edema inhibition values. The compounds proved to possess marginal or no ulcerogenic effect, as well as low systemic toxicity.
制备了几种新的1-甲基-5-[取代-4-氧代-1,2,3-苯并三嗪-3-基]-1H-吡唑-4-乙酸及其乙酯衍生物。对这些化合物进行了镇痛、抗炎活性、急性毒性、致溃疡作用以及作为3α-羟基类固醇脱氢酶（3α-HSD）体外抑制剂的测试，因为据称抑制这种酶可预测体内抗炎活性。在苯醌和乙酸腹膜炎试验中，一些化合物比保泰松更具活性，在角叉菜胶足爪水肿试验中与该药物活性相当。所有化合物均抑制3α-HSD，但未观察到与足爪水肿抑制值的相关性。这些化合物被证明具有轻微或无致溃疡作用以及低全身毒性。
