Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu 4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)

Darren W. Engers; Patrick R. Gentry; Richard Williams; Julie D. Bolinger; C. David Weaver; Usha N. Menon; P. Jeffrey Conn; Craig W. Lindsley; Colleen M. Niswender; Corey R. Hopkins

doi:10.1016/j.bmcl.2010.07.007

Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu ₄ positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)

Darren W. Engers, Patrick R. Gentry, Richard Williams, Julie D. Bolinger, C. David Weaver, Usha N. Menon, P. Jeffrey Conn, Craig W. Lindsley, Colleen M. Niswender, Corey R. Hopkins

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

Herein we disclose the synthesis and SAR of a series of 4-(phenylsulfamoyl)phenylacetamide compounds as mGlu₄ positive allosteric modulators (PAMs) that were identified via a functional HTS. An iterative parallel approach to these compounds culminated in the discovery of VU0364439 (11) which represents the most potent (19.8 nM) mGlu₄ PAM reported to date.

Original language	English (US)
Pages (from-to)	5175-5178
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	17
DOIs	https://doi.org/10.1016/j.bmcl.2010.07.007
State	Published - Sep 1 2010
Externally published	Yes

Keywords

Functional high-throughput screen (HTS)
Metabotropic glutamate receptor 4
mGlu

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2010.07.007

Cite this

Engers, D. W., Gentry, P. R., Williams, R., Bolinger, J. D., Weaver, C. D., Menon, U. N., Conn, P. J., Lindsley, C. W., Niswender, C. M., & Hopkins, C. R. (2010). Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu ₄ positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS). Bioorganic and Medicinal Chemistry Letters, 20(17), 5175-5178. https://doi.org/10.1016/j.bmcl.2010.07.007

Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu ₄ positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS). / Engers, Darren W.; Gentry, Patrick R.; Williams, Richard et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 17, 01.09.2010, p. 5175-5178.

Research output: Contribution to journal › Article › peer-review

Engers, DW, Gentry, PR, Williams, R, Bolinger, JD, Weaver, CD, Menon, UN, Conn, PJ, Lindsley, CW, Niswender, CM & Hopkins, CR 2010, 'Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu ₄ positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)', Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 17, pp. 5175-5178. https://doi.org/10.1016/j.bmcl.2010.07.007

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abstract = "Herein we disclose the synthesis and SAR of a series of 4-(phenylsulfamoyl)phenylacetamide compounds as mGlu4 positive allosteric modulators (PAMs) that were identified via a functional HTS. An iterative parallel approach to these compounds culminated in the discovery of VU0364439 (11) which represents the most potent (19.8 nM) mGlu4 PAM reported to date.",

keywords = "Functional high-throughput screen (HTS), Metabotropic glutamate receptor 4, mGlu",

author = "Engers, {Darren W.} and Gentry, {Patrick R.} and Richard Williams and Bolinger, {Julie D.} and Weaver, {C. David} and Menon, {Usha N.} and Conn, {P. Jeffrey} and Lindsley, {Craig W.} and Niswender, {Colleen M.} and Hopkins, {Corey R.}",

note = "Funding Information: The authors thank Qingwei Luo and Rocio Zamorano for technical assistance with pharmacology assays and Emily L. Days, Tasha Nalywajko, Cheryl A. Austin, and Michael Baxter Williams for their critical contributions to the HTS portion of the project and Matt Mulder, Chris Denicola, and Sichen Chang for the purification of compounds utilizing the mass-directed HPLC system. This work was supported by the National Institute of Mental Health , National Institute of Neurological Disorders, and Stroke , the Michael J. Fox Foundation , the Vanderbilt Department of Pharmacology , and the Vanderbilt Institute of Chemical Biology .",

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