A NOVEL 3-SUBSTITUTED BENZAZEPINONE GROWTH-HORMONE SECRETAGOGUE (L-692,429)

The 3-substituted benzazepinone, L-692,429 (compound 1), is the protot ype compound of a novel class of compounds that stimulate release of g rowth hormone (GH). The molecule evolved from efforts to identify a no n-peptide mimic of the growth hormone-releasing hexapeptide, GHRP-6. C ompound 1 is prepared by sequential attachment of dimethyl-beta-alanin e and 2'-biphenylyltetrazole side chains to a chiral 3-aminobenzolacta m nucleus. Comparison of the biological activity of 1 with the corresp onding six- and eight-membered lactam analogs shows the seven-membered benzazepinone skeleton to be preferred. Molecular modeling of the str ucturally diverse GH secretagogues, L-692,429 and GHRP-6, was performe d.