New active series of growth hormone secretagogues.
New growth hormone secretagogue (GHS) analogues were synthesized and evaluated for growth hormone releasing activity. This series derived from EP-51389 is based on a gem-diamino structure. Compounds that exhibited higher in vivo GH-releasing potency than hexarelin in rat (subcutaneous administration) were then tested per os in beagle dogs and for their binding affinity to human pituitary GHS receptors and to hGHS-R 1a. Compound 7 (JMV 1843, H-Aib-(d)-Trp-(d)-gTrp-formyl) showed high potency in these tests and was selected for clinical studies.(1)
Guerlavais
Vincent
V
Laboratoire des Aminoacides, Peptides et Protéines (LAPP), UMR 5810, Université Montpellier I et II, B.P. 14491, Faculté de Pharmacie, 15 Avenue Charles Flahaut, 34093 Montpellier Cédex 5, France.
Boeglin
Damien
D
Mousseaux
Delphine
D
Oiry
Catherine
C
Heitz
Annie
A
Deghenghi
Romano
R
Locatelli
Vittorio
V
Torsello
Antonio
A
Ghé
Corrado
C
Catapano
Filomena
F
Muccioli
Giampiero
G
Galleyrand
Jean-Claude
JC
Fehrentz
Jean-Alain
JA
Martinez
Jean
J
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D001667:Binding, Competitive; D002460:Cell Line; D004285:Dogs; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles; D007279:Injections, Subcutaneous; D008297:Male; D008566:Membranes; D008875:Middle Aged; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010902:Pituitary Gland / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D014364:Tryptophan / Q000031:analogs & derivatives
D007211:Indoles; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; C582727:macimorelin; D014364:Tryptophan; D013006:Growth Hormone