title: Nonnucleoside HIV-1 reverse transcriptase inhibitors; part 3. Synthesis and antiviral activity of 5-alkyl-2-[(aryl and alkyloxyl-carbonylmethyl)thio]-6-(1-naphthylmethyl) pyrimidin-4(3H)-ones.
abstract: A series of 6-naphthylmethyl substituted S-alkylated dihydroalkoxybenzyloxopyrimidine (S-DABO) analogues with a beta-carbonyl group on the C-2 side chain were synthesized. All of the new compounds were evaluated for their anti-HIV activities in MT-4 cells. The most active compound, 5-isopropyl-2-[(4'-methoxyphenylcarbonyl-methyl)thio]-6-(1-naphthylmethyl)pyrimidin-4(3H)-one showed activity against HIV-1 and against the double mutated strain of HIV(Y181C and K103N) in the micromolar range. Furthermore, some of the compounds are active against both HIV-1 and HIV-2 in cell culture. In view of the fact that the loss of antiviral activity of these compounds when tested against S0561945 was much less pronounced than the loss of activity of typical NNRTIs, it is concluded that some of the compounds might interfere with another target or act on reverse transcriptase in a different way than the typical NNRTIs.
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: He
authors.forename: Fener
authors.initials: F
authors.lastname: Chen
authors.forename: Xiongjie
authors.initials: X
authors.lastname: Yu
authors.forename: Yueping
authors.initials: Y
authors.lastname: Wang
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; D018360:Crystallography, X-Ray; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase