title: Non-nucleoside HIV reverse transcriptase inhibitors, Part 6[1]: synthesis and anti-HIV activity of novel 2-[(arylcarbonylmethyl)thio]-6-arylthio DABO analogues.
abstract: 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.
authors.affiliation: Department of Chemistry, Fudan University, Shanghai, People's Republic of China.
authors.forename: Guang-Fu
authors.initials: GF
authors.lastname: Sun
authors.forename: Yun-Yan
authors.initials: YY
authors.lastname: Kuang
authors.forename: Fen-Er
authors.initials: FE
authors.lastname: Chen
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase