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-
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- 作者：Lindsey C. Morris ; Kellie D. Nance ; Patrick R. Gentry ; Emily L. Days ; C. David Weaver ; Colleen M. Niswender ; Analisa D. Thompson ; Carrie K. Jones ; Chuck W. Locuson ; Ryan D. Morrison ; J. Scott Daniels ; Kevin D. Niswender ; Craig W. Lindsley
- 刊名：Journal of Medicinal Chemistry
- 出版年：2014
- 出版时间：December 11, 2014
- 年：2014
- 卷：57
- 期：23
- 页码：10192-10197
- 全文大小：314K
- ISSN：1520-4804
文摘
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.