We report the conformational analysis by 1H-NMR in DMSO and computer simulations involving distance geometry and molecular dynamics simulations of peptoid analogs of the cyclic hexapeptide c-[Phe11-Pro6-Phe7-D-Trp8-Lys9-Thr10] L-363,301 (the numbering refers to the positions in native somatostatin). The compounds c-[Phe11-Nphe6-Nal7-D-Trp8-Lys9-Thr10] (Nphe6-Nal7 analog 1), c-[Nal11-Nphe6-Phe7-D-Trp8-Lys9-Thr10] (Nal11-Nphe6 analog 2) and c-[Phe11-Nnal6-Phe7-D-Trp8-Lys9-Thr10] (Nnal6 analog 3), where Nphe denotes N-benzylglycine and Nnal denotes N-(1-naphthylmethyl)glycine, are subjected to SAR studies in order to investigate the influence of the bulky naphthyl aromatic ring on the conformation. The Nal11-Nphe6 and Nphe6-Nal7 analogs exhibit potent binding to the hsst2, hsst3 and hsst5 receptors, whereas the Nnal6 analog has decreased binding affinity to all receptors but is more selective towards the hsst2 than the other two analogs and L-363,301. The conformational search employing distance geometry, energy minimization and molecular dynamic simulations gives insight into the conformational flexibility of these analogs. The molecules adopt both cis and trans orientations of the peptide bond between residues 11 and 6. The cis isomers of these analogs adopt type II' beta-turns with D-Trp in the i + 1 position and type VIalpha beta-turns with the cis peptide bond between residues 6 and 11. The results of free and distance restrained molecular dynamics simulations at 300 K indicate that the Nphe6-Nal7 and Nal11-Nphe6 compounds adopt a preferred backbone conformation which can be described as 'folded' about residues 7 and 10. The Nnal6 analog, which binds less effectively to the hsst receptors, has a more flexible backbone structure than the Nal11-Nphe6 and Nphe6-Nal7 analogs and prefers a 'flat' structure with regard to the orientations about Phe7 and Thr10 during molecular dynamics simulations.