Yejella Rajendra Prasad, Atla Srinivasa Rao
Pharmaceutical Chemistry Division, University College of Pharmaceutical Sciences, Andhra University, Andhra Pradesh, India.
Chem Pharm Bull (Tokyo). 2011;59(9):1079-82. doi: 10.1248/cpb.59.1079.
Chalcone derivatives (3a-m) were prepared by condensing 4-aminoacetophenone with various substituted aromatic and hetero aromatic aldehydes according to Claisen-Schmidt condensation. These chalcones, on reaction with guanidine hydrochloride under basic alcoholic conditions gave 2,4,6-trisubstituted pyrimidines (5a-m) in quantitative yields. All the newly synthesized pyrimidines were characterized by means of IR, ¹H- and ¹³C-NMR, Electron Ionization (EI)-mass and elemental analyses and screened for anti-inflammatory and analgesic activities by in vivo. 2-amino-4-(4-aminophenyl)-6-(2,4-dichlorophenyl)pyrimidine (5b) and 2-amino-4-(4-aminophenyl)-6-(3-bromophenyl) pyrimidine (5d) were found to be the most potent anti-inflammatory and analgesic activity compared with ibuprofen, reference standard. And also it was found that compound 5b identified as lead structure among all in both the activities. Pyrimidines which showed good anti-inflammatory activity also displayed better analgesic activity.
根据克莱森-施密特缩合反应,通过4-氨基苯乙酮与各种取代的芳香醛和杂芳香醛缩合制备查尔酮衍生物(3a - m)。这些查尔酮在碱性乙醇条件下与盐酸胍反应,定量产率得到2,4,6-三取代嘧啶(5a - m)。所有新合成的嘧啶通过红外光谱、¹H-和¹³C-核磁共振、电子电离(EI)质谱和元素分析进行表征,并通过体内实验筛选其抗炎和镇痛活性。与参考标准布洛芬相比,发现2-氨基-4-(4-氨基苯基)-6-(2,4-二氯苯基)嘧啶(5b)和2-氨基-4-(4-氨基苯基)-6-(3-溴苯基)嘧啶(5d)具有最强的抗炎和镇痛活性。此外,还发现化合物5b在这两种活性中均被确定为先导结构。显示出良好抗炎活性的嘧啶也表现出较好的镇痛活性。