Discovery, synthesis, and structure-activity studies of tetrazole based growth hormone secretagogues.
A novel class of Growth Hormone Secretagogues (GHS), based on a tetrazole template, has been discovered. In vitro SAR and in vivo potency within this new class of GHS are described. The tetrazole 9q exhibits good oral bioavailability in rats and dogs as well as efficacy following an oral 10 mg/kg dose in dogs. Solution and solid phase protocols for the synthesis of tetrazole based GHS have been developed.
Hernández
Andrés S
AS
Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA. andres.hernandez@bms.com
Cheng
Peter T W
PT
Musial
Christa M
CM
Swartz
Stephen G
SG
George
Rocco J
RJ
Grover
Gary
G
Slusarchyk
Dorothy
D
Seethala
R Krishna
RK
Smith
Mark
M
Dickinson
Kenneth
K
Giupponi
Leah
L
Longhi
Daniel A
DA
Flynn
Neil
N
Murphy
Brian J
BJ
Gordon
David A
DA
Biller
Scott A
SA
Robl
Jeffrey A
JA
Tino
Joseph A
JA
D000818:Animals; D004285:Dogs; D013006:Growth Hormone / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D013777:Tetrazoles; D013006:Growth Hormone