Discovery of novel non-peptidic beta-alanine piperazine amide derivatives and their optimization to achiral, easily accessible, potent and selective somatostatin sst1 receptor antagonists

Thomas Troxler; Konstanze Hurth; Henri Mattes; Mahavir Prashad; Philippe Schoeffter; Daniel Langenegger; Albert Enz; Daniel Hoyer

doi:10.1016/j.bmcl.2009.01.072

Discovery of novel non-peptidic beta-alanine piperazine amide derivatives and their optimization to achiral, easily accessible, potent and selective somatostatin sst1 receptor antagonists

Bioorg Med Chem Lett. 2009 Mar 1;19(5):1305-9. doi: 10.1016/j.bmcl.2009.01.072. Epub 2009 Jan 27.

Authors

Thomas Troxler¹, Konstanze Hurth, Henri Mattes, Mahavir Prashad, Philippe Schoeffter, Daniel Langenegger, Albert Enz, Daniel Hoyer

Affiliation

¹ Novartis Institutes for BioMedical Research, Neuroscience Chemistry, WSJ-088.3.06, CH-4002 Basel, BS, Switzerland.

PMID: 19208473
DOI: 10.1016/j.bmcl.2009.01.072

Abstract

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.

Publication types

Comparative Study

MeSH terms

Animals
Dose-Response Relationship, Drug
Drug Discovery*
Humans
Mice
Piperazine
Piperazines / chemical synthesis*
Piperazines / metabolism
Piperazines / pharmacology
Protein Binding
Rats
Receptors, Somatostatin / antagonists & inhibitors*
Receptors, Somatostatin / physiology
Stereoisomerism
beta-Alanine / analogs & derivatives*
beta-Alanine / chemical synthesis
beta-Alanine / metabolism
beta-Alanine / pharmacology

Substances

Piperazines
Receptors, Somatostatin
somatostatin receptor type 1
beta-Alanine
Piperazine
beta-alanine amide