Fathalla O A, Zaki M E A, Swelam S A, Nofal S M, el-Eraky W I
Medicinal Chemistry Department, National Research Centre, Dokki, Cairo, Egypt.
Acta Pol Pharm. 2003 Jan-Feb;60(1):51-60.
Interaction of hydrazine hydrate with methyl (2-E)-2-cyano-3-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino]-3-(methylsulphanyl)-2-propenoate 2 which was obtained by the reaction of methyl-2-cyano-3,3-bis(methylsulphanyl) acrylate 1 with 4-amino-1-phenyl-2,3-dimethyl pyrazoline-5-one afforded methyl-5-amino-3-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino]-1H-pyrazole-4-carboxylate 3a. The pyrazolin derivative 3a is a good precursor for the synthesis of pyrazolo[1,5-a]pyrimidines which is based on the interaction of 3a with alpha,beta-unsaturated nitrile derivatives. The biological effects of some of the newly synthesized compounds were also investigated as antiinflammatory, analgesic and antipyretic drugs. Compounds 2b, 4a, 3a, 3b, 2a and 4b were found to have significant antiinflammatory activity in descending order in comparison to control groups phenylbutazone. Compounds 3a, 2a, 4b, 4a, 2b and 3b have analgesic activity in decreasing order. Compound 3a was the most potent and had 82.6% potency of Novalgin. Compounds 2b, 2a, 3b, 4b, 3a and 4a were found to have significant antipyretic activity in descending order. Compounds 2a, 4b induced no ulcerogenic activity, while compounds 3b, 2b, 4a and 3a showed only slight ulcerogenic activity.
水合肼与甲基(2-E)-2-氰基-3-[(1,5-二甲基-3-氧代-2-苯基-2,3-二氢-1H-吡唑-4-基)氨基]-3-(甲基硫烷基)-2-丙烯酸酯2相互作用，化合物2是由甲基-2-氰基-3,3-双(甲基硫烷基)丙烯酸酯1与4-氨基-1-苯基-2,3-二甲基吡唑啉-5-酮反应制得的，得到甲基-5-氨基-3-[(1,5-二甲基-3-氧代-2-苯基-2,3-二氢-1H-吡唑-4-基)氨基]-1H-吡唑-4-羧酸酯3a。吡唑啉衍生物3a是基于3a与α,β-不饱和腈衍生物相互作用合成吡唑并[1,5-a]嘧啶的良好前体。还研究了一些新合成化合物作为抗炎、镇痛和解热药物的生物活性。与对照组保泰松相比，发现化合物2b、4a、3a、3b、2a和4b具有显著的抗炎活性，活性由高到低依次排列。化合物3a, 2a, 4b, 4a, 2b和3b具有镇痛活性，活性由高到低依次排列。化合物3a活性最强，其效力为诺瓦经的82.6%。发现化合物2b、2a、3b、4b、3a和4a具有显著的解热活性，活性由高到低依次排列。化合物2a、4b未诱导溃疡形成活性，而化合物3b、2b、4a和3a仅表现出轻微的溃疡形成活性。
