title: Non-nucleoside HIV-1 reverse transcriptase inhibitors, Part 7. Synthesis, antiviral activity, and 3D-QSAR investigations of novel 6-(1-naphthoyl) HEPT analogues.
abstract: A series of novel 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) analogues bearing a 6-(1-naphthoyl) group of non-nucleoside human immunodeficiency virus (HIV) reverse transcriptase inhibitors were synthesized and evaluated for their activity against HIV-1 and HIV-2. It was found that most of these compounds showed good activity against HIV-1. Among them, compound 5-isopropyl-6-(1-naphthoyl)-1-[(2E)-3-phenylallyl]-2,4-pyrimidinedione (23) displayed the greatest inhibitory potency (IC(50)=0.14 muM), which is about 35-fold more active than HEPT and DDI. To rationalize the relationships between structure and activity of these novel compounds, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model was also generated. The results provided a tool for guiding the further design of more potent antiviral agents and for predicting the affinity of related compounds.
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ji
authors.forename: Fen-Er
authors.initials: FE
authors.lastname: Chen
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Feng
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 / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013941:Thymine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C061818:1-((2-hydroxyethoxy)methyl)-6-(phenylthio)thymine; D054303:HIV Reverse Transcriptase; D013941:Thymine