A novel 3-substituted benzazepinone growth hormone secretagogue (L-692,429).
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.
Schoen
W R
WR
Department of Basic Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065.
Pisano
J M
JM
Prendergast
K
K
Wyvratt
M J
MJ
Fisher
M H
MH
Cheng
K
K
Chan
W W
WW
Butler
B
B
Smith
R G
RG
Ball
R G
RG
D000595:Amino Acid Sequence; D000818:Animals; D001552:Benzazepines / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D013006:Growth Hormone / Q000031:analogs & derivatives; D008297:Male; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry / Q000494:pharmacology*
D001552:Benzazepines; D009842:Oligopeptides; D013777:Tetrazoles; C081455:L 692429; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone