Small molecule somatostatin receptor subtype-2 antagonists.
The first potent small molecule sst2 antagonists are reported. Altering known sst2 agonist molecules yielded compounds with high sst2 binding affinity and full antagonist activity. Compound 7a, for example, displaced somatostatin binding to the sst2 receptor with an IC(50)=2.9 nM and antagonized somatostatin action with an IC(50)=29nM.
Hay
B A
BA
Global Research and Development, Groton Laboratories, Pfizer Inc, Eastern Pt. Road, Groton, CT 06340-5146, USA. bruce_a_hay@groton.pfizer.com
Cole
B M
BM
DiCapua
F M
FM
Kirk
G W
GW
Murray
M C
MC
Nardone
R A
RA
Pelletier
D J
DJ
Ricketts
A P
AP
Robertson
A S
AS
Siegel
T W
TW
D008958:Models, Molecular; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013004:Somatostatin / Q000737:chemistry / Q000494:pharmacology*
D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2