Identification of structurally diverse growth hormone secretagogue agonists by virtual screening and structure-activity relationship analysis of 2-formylaminoacetamide derivatives

Two molecules with known growth hormone secretagogue (GHS) agonist activity were used as templates to computationally screen ∼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.