Modeling directed design and biological evaluation of quinazolinones as non-peptidic growth hormone secretagogues.
Quinazolinone derivatives were synthesized and evaluated as non-peptidic growth hormone secretagogues. Modeling guided design of quinazolinone compound 21 led to a potency enhancement of greater than 200-fold compared to human growth hormone secretagogue affinity of a screening lead 4.
Ye
Z
Z
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Gao
Y
Y
Bakshi
R K
RK
Chen
M H
MH
Rohrer
S P
SP
Feighner
S D
SD
Pong
S S
SS
Howard
A D
AD
Blake
A
A
Birzin
E T
ET
Locco
L
L
Parmar
R M
RM
Chan
W W
WW
Schaeffer
J M
JM
Smith
R G
RG
Patchett
A A
AA
Nargund
R P
RP
D000818:Animals; D001665:Binding Sites; D015195:Drug Design; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008958:Models, Molecular; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D012636:Secretory Rate / Q000187:drug effects; D013329:Structure-Activity Relationship
D011799:Quinazolines; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D019382:Human Growth Hormone