Discovery of (S)-2-Cyclopentyl-N-((1-isopropylpyrrolidin2-yl)-9-methyl-1-oxo-2,9-dihydro-1H-pyrrido[3,4-b]indole-4-carboxamide (VU0453379): A Novel, CNS Penetrant Glucagon-Like Peptide 1 Receptor (GLP-1R) Positive Allosteric Modulator (PAM)

[Image: see text] A duplexed, functional multiaddition high throughput screen and subsequent iterative parallel synthesis effort identified the first highly selective and CNS penetrant glucagon-like peptide-1R (GLP-1R) positive allosteric modulator (PAM). PAM (S)-9b potentiated low-dose exenatide to...

Descripción completa

Detalles Bibliográficos
Autores principales: Morris, Lindsey C., Nance, Kellie D., Gentry, Patrick R., Days, Emily L., Weaver, C. David, Niswender, Colleen M., Thompson, Analisa D., Jones, Carrie K., Locuson, Chuck W., Morrison, Ryan D., Daniels, J. Scott, Niswender, Kevin D., Lindsley, Craig W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266362/
https://www.ncbi.nlm.nih.gov/pubmed/25423411
http://dx.doi.org/10.1021/jm501375c
Descripción
Sumario:[Image: see text] A duplexed, functional multiaddition high throughput screen and subsequent iterative parallel synthesis effort identified the first highly selective and CNS penetrant glucagon-like peptide-1R (GLP-1R) positive allosteric modulator (PAM). PAM (S)-9b potentiated low-dose exenatide to augment insulin secretion in primary mouse pancreatic islets, and (S)-9b alone was effective in potentiating endogenous GLP-1R to reverse haloperidol-induced catalepsy.

Ejemplares similares