Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia.
Molecules. 2013 Dec 27;19(1):279-90. doi: 10.3390/molecules19010279.
5-Alkyl-6-(substituted benzyl)-2-thiouracils 3a,c were reacted with (2-chloroethyl) diethylamine hydrochloride to afford the corresponding 2-(2-diethylamino)ethylthiopyrimidin- 4(3H)-ones 4a,b. Reaction of 3a-c with N-(2-chloroethyl)pyrrolidine hydrochloride and/or N-(2-chloroethyl)piperidine hydrochloride gave the corresponding 2-[2-(pyrrolidin-1-yl)ethyl]-thiopyrimidin-4(3H)-ones 5a-c and 2-[2-(piperidin-1-yl)ethyl]thiopyrimidin-4(3H)-ones 6a,b, respectively. Treatment of 3a-d with N-(2-chloroethyl)morpholine hydrochloride under the same reaction conditions formed the corresponding 2-[2-(morpholin-4-yl)ethyl]thiopyrimidines 6c-f. On the other hand, 3a,b were reacted with N-(2-bromoethyl)phthalimide and/or N-(3-bromopropyl)phthalimide to furnish the corresponding 2-[2-(N-phthalimido)ethyl]-pyrimidines 7a,b and 2-[3-(N-phthalimido)-propyl]pyrimidines 7c,d, respectively. Compounds 3a-d, 4a,b, 5a-c, 6a-f and 7a-d were screened against Gram-positive bacteria (Staphylococcus aureus ATCC 29213, Bacillus subtilis NRRL 4219 and Bacillus cereus), yeast-like pathogenic fungus (Candida albicans ATCC 10231) and a fungus (Aspergillusniger NRRL 599). The best antibacterial activity was displayed by compounds 3a, 3b, 4a, 5a, 5b, 6d, 6f, 7b and 7d, whereas compounds 4b, 5b, 5c, 6a, 6b and 6f exhibited the best antifungal activity.
5-烷基-6-(取代苄基)-2-硫代尿嘧啶 3a,c 与(2-氯乙基)二乙胺盐酸盐反应，得到相应的 2-(2-二乙氨基)乙基硫代嘧啶-4(3H)-酮 4a,b。3a-c 与 N-(2-氯乙基)吡咯烷盐酸盐和/或 N-(2-氯乙基)哌啶盐酸盐反应，分别得到相应的 2-[2-(吡咯烷-1-基)乙基]-硫代嘧啶-4(3H)-酮 5a-c 和 2-[2-(哌啶-1-基)乙基]硫代嘧啶-4(3H)-酮 6a,b。3a-d 与 N-(2-氯乙基)吗啉盐酸盐在相同的反应条件下反应，形成相应的 2-[2-(吗啉-4-基)乙基]硫代嘧啶 6c-f。另一方面，3a,b 与 N-(2-溴乙基)邻苯二甲酰亚胺和/或 N-(3-溴丙基)邻苯二甲酰亚胺反应，分别得到相应的 2-[2-(N-邻苯二甲酰亚氨基)乙基]嘧啶 7a,b 和 2-[3-(N-邻苯二甲酰亚氨基)丙基]嘧啶 7c,d。化合物 3a-d、4a,b、5a-c、6a-f 和 7a-d 对革兰氏阳性菌(金黄色葡萄球菌 ATCC 29213、枯草芽孢杆菌 NRRL 4219 和蜡状芽孢杆菌)、酵母样致病真菌(白色念珠菌 ATCC 10231)和真菌(黑曲霉 NRRL 599)进行了筛选。化合物 3a、3b、4a、5a、5b、6d、6f、7b 和 7d 表现出最好的抗菌活性，而化合物 4b、5b、5c、6a、6b 和 6f 表现出最好的抗真菌活性。
