DB02

A novel series of dihydro-hydroxyl-phene-thylsulfanyl-ω-cyclohexyl/phenyl-oxopyrimidine derivatives have been synthesized and their in vitro anti-hepatitis C virus activities have been evaluated using Huh 7.5.1 cells.Some of the compounds showed moderate anti-hepatitis C virus activities, with EC₅₀ range from 7.53 to 0.13 μM.Among all the compounds, 6-(cyclohexylmethyl)-5-ethyl-2-((2-hydroxy-2-phenylethyl)thio)-pyrimidin-4 (3H)-one (3a) had the most promising potential in inhibiting hepatitis C virus with an EC₅₀ value of 0.13 μM and SI value of 121.It was noticed that some of these compounds are both active on hepatitis C virus and human immunodeficiency virus.In addition to exptl. evaluation, structure-activity relationships and the mol. modeling anal. of these new congeners are also discussed.

Novel 5-alky-6-(cyclohexylmethyl)-2-[(2-hydroxy-2-phenylethyl)thio]-4(3H)-pyrimidinone derivatives were synthesized and evaluated for their ability to inhibit HIV.The screening results revealed that several compounds displayed inhibiting activity against HIV.Two compounds in particular, showed a l potent anti-HIV activities with EC₅₀ values of 0.003μM and CC₅₀ values of 200 μM.A preliminary structure-activity relationship (SAR) and mol. modeling analyses of these newly synthesized hydroxyphenethyl-S-DACOs are also discussed.The title compounds thus formed included 6-(cyclohexylmethyl)-5-ethyl-2-[[2-hydroxy-2-(4-hydroxyphenyl)ethyl]thio]-4(3H)-pyrimidinone (I) and related substances, such as 6-(cyclohexylmethyl)-2-[[2-(4-fluorophenyl)-2-hydroxyethyl]thio]-5-methyl-4(3H)-pyrimidinone.The synthesis of the target compounds was achieved by a reduction of 6-(cyclohexylmethyl)-5-ethyl-2-[(2-oxo-2-phenylethyl)thio]-4(3H)-pyrimidinone and similar compounds [oxophenylethyl-S-DACO derivatives].