Synthesis and biological activities of phenyl piperazine-based peptidomimetic growth hormone secretagogues.
A new class of potent, orally active phenyl piperazine-based GH secretagogues have been discovered from attempts to mimic the arrangement of the phenyl substituent in the spiroindanyl piperidine and spiroindoline sulfonamide privileged structures of 4 and 1, respectively. The best of these compounds, 18 (EC50 = 2.8 nM) is nearly as potent as MK-0677 for releasing GH from rat pituitary cells.
Barakat
K J
KJ
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Cheng
K
K
Chan
W W
WW
Butler
B S
BS
Jacks
T M
TM
Schleim
K D
KD
Hora
D F
DF
Hickey
G J
GJ
Smith
R G
RG
Patchett
A A
AA
Nargund
R P
RP
D000818:Animals; D002478:Cells, Cultured; D015195:Drug Design; D013006:Growth Hormone / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013141:Spiro Compounds / Q000494:pharmacology; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
C117574:1-(2-(2-amino-2-methylpropanamido)-5-phenylpentanoyl)-4-(4-(1-methylethylsulfonamido)phenyl)piperazine; D007211:Indoles; D010455:Peptides; D010879:Piperazines; D013141:Spiro Compounds; D013449:Sulfonamides; D013006:Growth Hormone; C094817:ibutamoren mesylate