title: Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 2: Parallel synthesis, molecular modelling and structure-activity relationship studies on analogues of O-(2-phenylethyl)-N-phenylthiocarbamate.
abstract: To acquire further insight into the structure-activity relationship (SAR) of the thiocarbamates (TCs) described in the preceding work, 57 analogues of the lead compound O-(2-phenylethyl)-N-phenylthiocarbamate I were prepared by parallel solution-phase synthesis. We varied the 2-phenylethyl moiety (mono-substitution on the phenyl ring and modification of the ethyl linker), keeping constant the N-phenyl ring substitutions which have given the best results in the previous series. Most of the new TCs inhibited wild-type HIV-1 at micro- and nanomolar concentrations in MT-4 cell-based assays. Some TCs were also active at micromolar concentrations against the Y181C and/or K103N/Y181C resistant mutants. The SARs were rationalized by docking simulations.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV 3, I-16132 Genova, Italy. sara.cesarini@unige.it
authors.forename: Sara
authors.initials: S
authors.lastname: Cesarini
authors.forename: Andrea
authors.initials: A
authors.lastname: Spallarossa
authors.forename: Angelo
authors.initials: A
authors.lastname: Ranise
authors.forename: Olga
authors.initials: O
authors.lastname: Bruno
authors.forename: Paolo
authors.initials: P
authors.lastname: La Colla
authors.forename: Barbara
authors.initials: B
authors.lastname: Secci
authors.forename: Gabriella
authors.initials: G
authors.lastname: Collu
authors.forename: Roberta
authors.initials: R
authors.lastname: Loddo
mesh_terms: D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology*; D008958:Models, Molecular; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors; D013859:Thiocarbamates