Abstract

2-Methylsulfanyl-1,4-dihydropyrimidine derivatives were synthesized by alkylation of 1,2,3,4-tetrahydropyrimidines with methyl iodide in the presence of pyridine. Their structures were confirmed by spectrometric charachterisation. In silico ADME and physicochemical properties are calculated using swissADME software. All compounds tested for analgesic activity by acetic acid-induced writhing method. The compounds ethyl 4-(4-ethenylphenyl)-2-(methylsulfanyl)-1,4-dihydropyrimidine-5-carboxylate (IIh) and ethyl 2-(methylsulfanyl)-4-[4-(propan-2-yl)phenyl]-1,4-dihydropyrimidine-5-carboxylate (IIl) exhibited maximum analgesic activity. Compounds methyl 4-(3-chlorophenyl)-2-(methylsulfanyl)-1,4-dihydropyrimidine-5-carboxylate, ethyl 4-(3-chlorophenyl)-2-(methylsulfanyl)-1,4-dihydropyrimidine-5-carboxylate, methyl 4-(4-ethenylphenyl)-2-(methylsulfanyl)-1,4-dihydropyrimidine-5-carboxylate and methyl 2-(methylsulfanyl)-4-[4-(propan-2-yl)phenyl]-1,4-dihydropyrimidine-5-carboxylate showed good activity. The remaining compounds showed moderate analgesic activity. In vitro cyclooxygenase, COX-2 inhibition assay performed using COX 2 (human) inhibitor screening assay kit. Title compounds exhibited inhibitory activity against COX-2 (IC₅₀ = 0.66–0.87 µM).

中文翻译：

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2-甲硫基-1,4-二氢嘧啶类镇痛衍生物的设计、合成及药理评价

摘要

在吡啶存在下，用碘甲烷对1,2,3,4-四氢嘧啶进行烷基化，合成2-甲基硫基-1,4-二氢嘧啶衍生物。它们的结构通过光谱表征得到证实。使用 swissADME 软件计算计算机 ADME 和物理化学性质。通过乙酸诱导扭体法测试所有化合物的镇痛活性。化合物4-(4-乙烯基苯基)-2-(甲硫基)-1,4-二氢嘧啶-5-甲酸乙酯( IIh )和2-(甲硫基)-4-[4-(丙-2-基)苯基乙酯]-1,4-二氢嘧啶-5-羧酸酯（IIl）表现出最大的镇痛活性。化合物 4-(3-氯苯基)-2-(甲硫基)-1,4-二氢嘧啶-5-甲酸甲酯、4-(3-氯苯基)-2-(甲硫基)-1,4-二氢嘧啶-5-甲酸乙酯、4-(4-乙烯基苯基)-2-(甲硫基)-1,4-二氢嘧啶-5-甲酸甲酯和2-(甲硫基)-4-[4-(丙-2-基)苯基]-1， 4-二氢嘧啶-5-羧酸酯显示出良好的活性。其余化合物显示出中等的镇痛活性。使用 COX 2（人）抑制剂筛选测定试剂盒进行体外环氧合酶、COX-2 抑制测定。标题化合物表现出对 COX-2 的抑制活性 (IC ₅₀ = 0.66–0.87 µM)。