In order to expand the structure-activity relationship (SAR) studies on Thiocarbamates (TCs), a recently discovered class of potent non-nucleoside HIV-1 reverse transcriptase inhibitors, 38 analogues of the lead O-[2-(2-pyridyl)ethyl]-N-phenylthiocarbamate 1 were prepared by parallel solution-phase synthesis. The SAR strategy was focused on the variation (mono- and disubstitution) of the N-phenyl ring and the replacement of the 2-pyridyl with 4-pyridyl, 2-thienyl and phenyl rings. The majority of the new TCs proved to prevent the wild-type HIV-1 multiplication in MT-4 cell culture and the most potent congeners displayed an EC(50) value of 100 nM. Two TCs were active also at micromolar concentrations against the Y181C- and/or K103N/Y181C-resistant mutants. Docking simulations helped to rationalize the SARs.