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...

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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
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author 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.
author_facet 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.
author_sort Morris, Lindsey C.
collection PubMed
description [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.
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spelling pubmed-42663622015-11-25 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) 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. J Med Chem [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. American Chemical Society 2014-11-25 2014-12-11 /pmc/articles/PMC4266362/ /pubmed/25423411 http://dx.doi.org/10.1021/jm501375c Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle 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.
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)
title 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)
title_full 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)
title_fullStr 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)
title_full_unstemmed 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)
title_short 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)
title_sort 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)
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266362/
https://www.ncbi.nlm.nih.gov/pubmed/25423411
http://dx.doi.org/10.1021/jm501375c
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