Discovery of a tetrazole-based growth hormone secretagogue: 4-(hydroxybutyl)carbamic acid 2-{5-[1-(2-amino-2-methylpropionylamino)-2- benzyloxyethyl]tetrazol-1-yl}ethyl ester (BMS-317180).
A tetrazole-based peptidomimetic 2 (BMS-317180) was discovered as a human growth hormone secretagogue (GHS). Compound 2 is a potent, novel, orally effective GHS that shows an excellent safety profile in preclinical studies. The compound was advanced into clinical development.
Li
Jun
J
Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 5400, Princeton, NJ 08543, USA. jun.li@bms.com
Chen
Stephanie Y
SY
Li
James J
JJ
Wang
Haixia
H
Hernandez
Andres S
AS
Tao
Shiwei
S
Musial
Christa M
CM
Qu
Fucheng
F
Swartz
Stephen
S
Chao
Sam T
ST
Flynn
Neil
N
Murphy
Brian J
BJ
Slusarchyk
Dorothy A
DA
Seethala
Ramakrishna
R
Yan
Mujing
M
Sleph
Paul
P
Grover
Gary
G
Smith
Mark A
MA
Beehler
Blake
B
Giupponi
Leah
L
Dickinson
Kenneth E
KE
Zhang
Hongjian
H
Humphreys
William G
WG
Patel
Bharat P
BP
Schwinden
Mark
M
Stouch
Terry
T
Cheng
Peter T W
PT
Biller
Scott A
SA
Ewing
William R
WR
Gordon
David
D
Robl
Jeffrey A
JA
Tino
Joseph A
JA
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002219:Carbamates / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D004285:Dogs; D004952:Esters; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D008252:Macaca fascicularis; D051381:Rats; D012995:Solubility; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D014867:Water
C526808:4-(hydroxybutyl)carbamic acid 2-(5-(1-(2-amino-2-methylpropionylamino)-2-benzyloxyethyl)tetrazol-1-yl)ethyl ester; D002219:Carbamates; D004952:Esters; D013777:Tetrazoles; D014867:Water; D019382:Human Growth Hormone; D013006:Growth Hormone