Piperidinyl-nicotinamides as potent and selective somatostatin receptor subtype 5 antagonists.
Nicotinamides of benzyl-substituted 4-aminopiperidines and their seven-membered analogs of generic structure 2 and 2' have been discovered as potent and selective SST5 antagonists. The activity (K(i)) ranges from 2.4 to 436 nM. Most compounds exhibit decent physicochemical properties and follow a clear SAR pattern. Interestingly enough, the receptor is strongly enantiodiscriminating and binds in the amino-azepane-series only the (R)-enantiomer.
Alker
André
A
F. Hoffmann-La Roche Ltd, Pharmaceuticals Division, Molecular Structure Research, CH-4070 Basel, Switzerland.
Binggeli
Alfred
A
Christ
Andreas D
AD
Green
Luke
L
Maerki
Hans Peter
HP
Martin
Rainer E
RE
Mohr
Peter
P
D001593:Benzyl Compounds / Q000737:chemistry*; D009536:Niacinamide / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010880:Piperidines / Q000737:chemistry; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C481395:4-aminopiperidine; D001593:Benzyl Compounds; D010880:Piperidines; D017481:Receptors, Somatostatin; D009536:Niacinamide; C094573:somatostatin receptor 5