Sun Guang-Fu, Kuang Yun-Yan, Chen Fen-Er, De Clercq Erik, Balzarini Jan, Pannecouque Christophe
Department of Chemistry, Fudan University, Shanghai, People's Republic of China.
Arch Pharm (Weinheim). 2005 Oct;338(10):457-61. doi: 10.1002/ardp.200400961.
2-(Arylcarbonylmethyl)thio-6alpha-naphthylmethyl derivatives of dihydro-alkoxy-benzyl-oxopyrimidines (DABO) were newly found to exhibit activity against both HIV-1 and HIV-2. To further explore their structure-activity relationship, the modified S-DABO analogues (5a-g and 6e-f) with a 1-naphthylthio or phenylthio group at the C-6 position were synthesized. S-Alkylation of 5-ethyl-2-thiouracil with substituted 2-bromo-acetophenones provided crude 2-[(arylcarbonylmethyl)thio]-5-ethyl-(3H)-uracil 2a-e, which was directly subjected to toluenesulfonylation with TsCl to afford disulfonate 4a-e. Substitution of 4a-e with arylthiol afforded the desired S-DABO analogues 5a-g and 6e-f. The compounds were evaluated for their in vitro anti-HIV activity in MT-4 cells. The IC(50) values for anti-HIV-1 activity fall into the range 0.37-29.50 microM, and the IC(50) values for anti-HIV-2 activity fall into the range 23.11-181.07 microM. The results indicated that these compounds are moderately active against HIV-1 and HIV-2.
二氢烷氧基苄基氧代嘧啶（DABO）的2-（芳基羰基甲基）硫代-6α-萘基甲基衍生物最近被发现对HIV-1和HIV-2均具有活性。为了进一步探究它们的构效关系，合成了在C-6位带有1-萘硫基或苯硫基的修饰S-DABO类似物（5a-g和6e-f）。5-乙基-2-硫脲与取代的2-溴苯乙酮进行S-烷基化反应得到粗品2-[(芳基羰基甲基)硫代]-5-乙基-(3H)-尿嘧啶2a-e，其直接与对甲苯磺酰氯进行甲苯磺酰化反应得到二磺酸酯4a-e。4a-e与芳硫醇发生取代反应得到所需的S-DABO类似物5a-g和6e-f。在MT-4细胞中对这些化合物的体外抗HIV活性进行了评估。抗HIV-1活性的IC(50)值在0.37 - 29.50微摩尔范围内，抗HIV-2活性的IC(50)值在23.11 - 181.07微摩尔范围内。结果表明这些化合物对HIV-1和HIV-2具有中等活性。
