与烯丙基反应-,乙酰-,在3-氨基-4,6-二甲基吡啶-2(1H)-酮的基础上研究了异硫氰酸苯酯,3-氨基-4-苯基吡啶-2-酮,和3-氨基-4-(噻吩-2-基)吡啶-2(1H)-酮(苯甲酰基-)异硫氰酸酯,得到相应的硫脲衍生物8-11a-c。与标准药物阿卡波糖相比,获得了十二种硫脲衍生物,并研究了它们对α-葡萄糖苷酶的抗糖尿病活性。比较药物阿卡波糖在15mM的浓度下抑制α-葡糖苷酶的活性达46.1%(阿卡波糖的IC50为11.96mM)。根据所进行的研究的结果,结果表明,烷基和苯基硫脲衍生物8,9a-c,与它们的乙酰基-(苯甲酰基)衍生物和10,11a-c相反,显示高抗糖尿病活性。因此,1-(4,6-二甲基-2-氧代-1,2-二氢吡啶-3-基)-3-苯基硫脲9a对酶α-葡萄糖苷酶具有最高的抑制活性,超过比较药物阿卡波糖的活性,其在15mm的浓度下抑制α-葡糖苷酶的活性56.6%(IC50=9,77mM)。1-(6-甲基-2-氧代4-(噻吩-2-基)-1,2-二氢吡啶-3-基)-3-苯基硫脲9c对酶α-葡萄糖苷酶具有抑制活性,与比较药物阿卡波糖相当,抑制α-葡萄糖苷酶的活性,浓度为15mm/41.2%(IC50=12,94mM)。化合物8a,8b,和9b显示出抑制酶α-葡萄糖苷酶的活性,与阿卡波糖相比活性较低,抑制浓度为15mM的α-葡萄糖苷酶的活性23.3%,26.9%,和35.2%,分别。化合物8a对α-葡萄糖苷酶的IC50,8b,发现9b为16.64mM,19.79mM,和21.79mM,分别。其他化合物8c,10a,10b,10c,11a,11b,和11c未显示对α-葡糖苷酶的抑制活性。因此,基于3-氨基吡啶-2(1H)-酮的新合成的硫脲衍生物是进一步修饰和研究其潜在抗糖尿病活性的有希望的候选者。这些积极的生物分析结果将刺激进一步深入的研究,包括体内模型。
Reactions with allyl-, acetyl-, and phenylisothiocyanate have been studied on the basis of 3-amino-4,6-dimethylpyridine-2(1H)-one, 3-amino-4-phenylpyridine-2-one, and 3-amino-4-(thiophene-2-yl)pyridine-2(1H)-one (benzoyl-)
isothiocyanates, and the corresponding thioureide derivatives 8-11a-c were obtained. Twelve thiourea derivatives were obtained and studied for their anti-diabetic activity against the enzyme α-glucosidase in comparison with the standard drug acarbose. The comparison drug acarbose inhibits the activity of α-glucosidase at a concentration of 15 mM by 46.1% (IC50 for acarbose is 11.96 mM). According to the results of the conducted studies, it was shown that alkyl and phenyl thiourea derivatives 8,9a-c, in contrast to their acetyl-(benzoyl) derivatives and 10,11a-c, show high antidiabetic activity. Thus, 1-(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)-3-phenylthiourea 9a has the highest inhibitory activity against the enzyme α-glucosidase, exceeding the activity of the comparison drug acarbose, which inhibits the activity of α-glucosidase by 56.6% at a concentration of 15 mm (IC50 = 9,77 mM). 1-(6-methyl-2-oxo 4-(thiophen-2-yl)-1,2-dihydropyridin-3-yl)-3-phenylthiourea 9c has inhibitory activity against the enzyme α-glucosidase, comparable to the comparison drug acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mm per 41.2% (IC50 = 12,94 mM). Compounds 8a, 8b, and 9b showed inhibitory activity against the enzyme α-glucosidase, with a lower activity compared to acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mM by 23.3%, 26.9%, and 35.2%, respectively. The IC50 against α-glucosidase for compounds 8a, 8b, and 9b was found to be 16.64 mM, 19.79 mM, and 21.79 mM, respectively. The other compounds 8c, 10a, 10b, 10c, 11a, 11b, and 11c did not show inhibitory activity against α-glucosidase. Thus, the newly synthesized derivatives of thiourea based on 3-aminopyridine-2(1H)-ones are promising candidates for the further modification and
study of their potential anti-diabetic activity. These positive bioanalytical results will stimulate further in-depth studies, including in vivo models.