ibutamoren-mesylate and tabimorelin

Topics: Benzazepines; Clinical Trials, Phase I as Topic; Dipeptides; Drug Design; Dwarfism, Pituitary; Ethylamines; Feeding and Eating Disorders; Ghrelin; Growth Hormone; Humans; Ileus; Indoles; Oligopeptides; Peptide Hormones; Sleep Wake Disorders; Spiro Compounds; Stimulation, Chemical; Tetrazoles

A series of NN703 analogues with lysine mimetics combined with naphthyl- or biphenylalanine in the core has been prepared and tested in vitro in a rat pituitary cell based assay and subsequently in vivo in pigs in a single dose at 50 nmol/kg. Re-introduction of certain pharmacophores in the C-terminal of NN703, which were originally removed during optimisation for oral bioavailability, led to unexpectedly potent compounds in vitro as well as in vivo.

Topics: Administration, Oral; Animals; Biological Availability; Cells, Cultured; Dipeptides; Growth Hormone; Hormones; Indoles; Oligopeptides; Pituitary Gland; Rats; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Receptors, Ghrelin; Spiro Compounds; Structure-Activity Relationship; Swine

The C-terminal the orally active growth hormone secretagogue NN703 was changed to prepare analogues with inverse sulfonamides and inverse amides. The compounds showed high activity in a in vitro rat pituitary model.

Topics: Animals; Dipeptides; Indoles; Kinetics; Rats; Spiro Compounds; Sulfonamides