Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Feb 24;54(4):1106-10.
doi: 10.1021/jm101271s. Epub 2011 Jan 19.

Discovery, synthesis, and structure-activity relationship development of a series of N-(4-acetamido)phenylpicolinamides as positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)) with CNS exposure in rats

Darren W Engers  1 , Julie R Field, Uyen Le, Ya Zhou, Julie D Bolinger, Rocio Zamorano, Anna L Blobaum, Carrie K Jones, Satyawan Jadhav, C David Weaver, P Jeffrey Conn, Craig W Lindsley, Colleen M Niswender, Corey R Hopkins
Affiliations

Discovery, synthesis, and structure-activity relationship development of a series of N-(4-acetamido)phenylpicolinamides as positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)) with CNS exposure in rats

Darren W Engers et al. J Med Chem. .

Abstract

Herein we report the discovery, synthesis, and evaluation of a series of N-(4-acetamido)-phenylpicolinamides as positive allosteric modulators of mGlu(4). Compounds from the series show submicromolar potency at both human and rat mGlu(4). In addition, pharmacokinetic studies utilizing subcutaneous dosing demonstrated good brain exposure in rats.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Structures of 1 and other recently reported mGlu4 PAMs.
Figure 2
Figure 2
Structure of initial HTS hit.
Scheme 1
Scheme 1
Synthesis of N-(4-acetamido)-phenylcarboxamides, 9, 10, and 12. All library compounds were purified by mass-directed prep LC where required.,
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Conn PJ, Pin J-P. Pharmacology and functions of metabotropic glutamate receptors. Ann. Rev. Pharmacol. Toxicol. 1997;37:205–237. - PubMed
    1. Schoepp DD, Jane DE, Monn JA. Pharmacological agents acting at subtypes of metabotropic glutamate receptors. Neuropharmacology. 1999;38:1431–1476. - PubMed
    1. Conn PJ, Christopoulos A, Lindsley CW. Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders. Nature Rev. Drug. Dis. 2009;8:41–54. - PMC - PubMed
    1. May LT, Leach K, Sexton PM, Christopoulos A. Allosteric modulation of G protein-coupled receptors. Annu. Rev. Pharmacol. Toxicol. 2007;47:1–51. - PubMed
    1. Johnson MP, Nisenbaum ES, Large TH, Emkey R, Baez M, Kingston AE. Allosteric modulators of metabotropic glutamate receptors: lessons learnt from mGlu1, mGlu2 and mGlu5 potentiators and antagonists. Biochem. Soc. Trans. 2004;32:881–887. - PubMed

Publication types

Substances

LinkOut - more resources