SAR of the arylpiperazine moiety of obeline somatostatin sst1 receptor antagonists.
The SAR of over 50 derivatives of octahydrobenzo[g]quinoline (obeline)-type somatostatin sst(1) receptor antagonist 1 is presented, focusing on the modification of its arylpiperazine moiety. Sst(1) affinities in this series cover a range of five orders of magnitude with the best derivatives displaying subnanomolar sst(1) affinities and >10,000-fold selectivities over the sst(2) receptor subtype as well as promising pharmacokinetic properties.
Hurth
Konstanze
K
Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. konstanze.hurth@novartis.com
Enz
Albert
A
Floersheim
Philipp
P
Gentsch
Conrad
C
Hoyer
Daniel
D
Langenegger
Daniel
D
Neumann
Peter
P
Pfäffli
Paul
P
Sorg
Dieter
D
Swoboda
Robert
R
Vassout
Annick
A
Troxler
Thomas
T
D008164:Luminescent Proteins / Q000737:chemistry / Q000494:pharmacology*; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D008164:Luminescent Proteins; D010879:Piperazines; D017481:Receptors, Somatostatin; C010497:obelin