Conformationally restricted peptidomimetics comprising eight stereoisomeric scaffolds with three-dimensional structural diversity were designed based on the structural features of cyclopropane, that is, cyclopropylic strain, which mimic wide-ranging tetrapeptide conformations covering β-turns through β-strands. Stereoselective synthesis of the designed peptidomimetics led to the identification of nonpeptidic melanocortin-4 receptor ligands.

A conformationally restricted privileged structure library with stereochemical diversity for a "fragment growth" methodology comprising 90 compounds was designed and systematically and efficiently synthesized using sulfur-modified Au-supported Pd (SAPd)-catalyzed ligand-free Suzuki-Miyaura coupling of vinyl iodide promoted by microwave and subsequent amidation in liquid-phase combinatorial chemistry as key reactions. Evaluation of the compounds with a 20-kinase panel indicated the usefulness of this "fragment growth" methodology for finding hit library compounds for fragment-based drug discovery.

Two molecules with known growth hormone secretagogue (GHS) agonist activity were used as templates to computationally screen approximately 80000 compounds. A total of 108 candidate compounds were selected, and five of them were found to be active in the low-micromolar range in both cell-based and direct binding assays. These compounds were structurally diverse and significantly differed from known GHS agonists. The most active compound was subjected to SAR evaluation, which slightly increased its potency and identified molecular regions important for specific GHS agonist activity.

A convenient synthesis of optically active 3-morpholinecarboxylic acid and its thio analogue, tetrahydro-2H-1,4-thiazine-3-carboxylic acid, has been developed. These intermediates were obtained by reaction of benzyl (S)-N-benzyloxycarbonyl-2-aziridinecarboxylate and its enantiomer with 2-chloroethanol or 2-chloroethanethiol, respectively.