Discovery of novel non-peptidic beta-alanine piperazine amide derivatives and their optimization to achiral, easily accessible, potent and selective somatostatin sst1 receptor antagonists.
Structural simplification of the core moieties of obeline and ergoline somatostatin sst(1) receptor antagonists, followed by systematic optimization, led to the identification of novel, highly potent and selective sst(1) receptor antagonists. These achiral, non-peptidic compounds are easily prepared and show promising PK properties in rodents.
Troxler
Thomas
T
Novartis Institutes for BioMedical Research, Neuroscience Chemistry, WSJ-088.3.06, CH-4002 Basel, BS, Switzerland.
Hurth
Konstanze
K
Mattes
Henri
H
Prashad
Mahavir
M
Schoeffter
Philippe
P
Langenegger
Daniel
D
Enz
Albert
A
Hoyer
Daniel
D
D000818:Animals; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D051379:Mice; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000502:physiology; D013237:Stereoisomerism; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology
D010879:Piperazines; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; D015091:beta-Alanine; D000077489:Piperazine; C012731:beta-alanine amide