Journal of Medicinal Chemistry · 1994 · 102 citations · 0 references
Life SciencesMedicinal ChemistryPharmacologyDrug DesignDrug DiscoveryHormone BiochemistryEndocrine PharmacologyGrowth HormoneGrowth Hormone RegulationHormone ReleaseHormone SecretionHormone StructureBiological Activity FeaturesG-protein-coupled Receptor Signaling In SecretionGrowth Hormone FamilyGrowth Hormone FunctionGrowth Hormone SignalingGrowth Hormone StructureReleasing HormonesSubstituent Effects On Biological Activity
The 3-substituted benzazepinone, L-692,429 (compound 1), is the prototype compound of a novel class of compounds that stimulate release of growth hormone (GH). The molecule evolved from efforts to identify a non-peptide mimic of the growth hormone-releasing hexapeptide, GHRP-6. Compound 1 is prepared by sequential attachment of dimethyl-beta-alanine and 2'-biphenylyltetrazole side chains to a chiral 3-aminobenzolactam nucleus. Comparison of the biological activity of 1 with the corresponding six- and eight-membered lactam analogs shows the seven-membered benzazepinone skeleton to be preferred. Molecular modeling of the structurally diverse GH secretagogues, L-692,429 and GHRP-6, was performed.