Discovery and characterization of a novel series of N-phenylsulfonyl-1H-pyrrole picolinamides as positive allosteric modulators of the metabotropic glutamate receptor 4 (mGlu4)

被引：5

作者：

Gogliotti, Rocco D. ^{[1
,2
]}

Blobaum, Anna L. ^{[1
,2
]}

Morrison, Ryan M. ^{[1
,2
]}

Daniels, J. Scott ^{[1
,2
]}

Salovich, James M. ^{[1
,2
]}

Cheung, Yiu-Yin ^{[1
,2
]}

Rodriguez, Alice L. ^{[1
,2
]}

Loch, Matthew T. ^{[1
,2
]}

Conn, P. Jeffrey ^{[1
,2
,3
]}

Lindsley, Craig W. ^{[1
,2
,4
]}

Niswender, Colleen M. ^{[1
,2
,3
]}

Hopkins, Corey R. ^{[1
,2
,4
]}

机构：

[1] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA

[3] Vanderbilt Univ, Vanderbilt Kennedy Ctr, Nashville, TN 37232 USA

[4] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 13期

关键词：

Metabotropic glutamate receptor 4; Positive allosteric modulator (PAM); Pyrrole sulfonamide; Phenyl replacement; PK; PARKINSONS-DISEASE; RECENT PROGRESS; RODENT MODELS; L-DOPA; SCHIZOPHRENIA; THERAPEUTICS; DISORDERS; EFFICACY; TARGETS; POTENT;

D O I：

10.1016/j.bmcl.2016.05.029

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Herein we report the synthesis and characterization of a novel series of N-phenylsulfonyl-1H-pyrrole picolinamides as novel positive allosteric modulators of mGlu(4). We detail our work towards finding phenyl replacements for the core scaffold of previously reported phenyl sulfonamides and phenyl sulfone compounds. Our efforts culminated in the identification of N-(1-((3,4-dimethylphenyl)sulfonyl)-1H-pyrrol-3-yl)picolinamide as a potent PAM of mGlu(4). (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：2984 / 2987

页数：4

共 30 条

[1] The mGIuR theory of fragile X mental retardation
Bear, MF
Huber, KM
Warren, ST
[J]. TRENDS IN NEUROSCIENCES, 2004, 27 (07) : 370 - 377
[2] Synergy between L-DOPA and a novel positive allosteric modulator of metabotropic glutamate receptor 4: Implications for Parkinson's disease treatment and dyskinesia
Bennouar, Khaled-Ezaheir
Uberti, Michelle A.
Melon, Christophe
Bacolod, Maria D.
Jimenez, Hermogenes N.
Cajina, Manuel
Goff, Lydia Kerkerian-Le
Doller, Dario
Gubellini, Paolo
[J]. NEUROPHARMACOLOGY, 2013, 66 : 158 - 169
[3] Solution-Phase Parallel Synthesis and SAR of Homopiperazinyl Analogs as Positive Allosteric Modulators of mGlu4
Cheung, Yiu-Yin
Zamorano, Rocio
Blobaum, Anna L.
Weaver, C. David
Conn, P. Jeffrey
Lindsley, Craig W.
Niswender, Colleen M.
Hopkins, Corey R.
[J]. ACS COMBINATORIAL SCIENCE, 2011, 13 (02) : 159 - 165
[4] Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia
Conn, P. Jeffrey
Lindsley, Craig W.
Jones, Carrie K.
[J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 2009, 30 (01) : 25 - 31
[5] Metabotropic glutamate receptors in the basal ganglia motor circuit
Conn, PJ
Battaglia, G
Marino, MJ
Nicoletti, F
[J]. NATURE REVIEWS NEUROSCIENCE, 2005, 6 (10) : 787 - 798
[6] Discovery, Synthesis, and Structure-Activity Relationship Development of a Series of N-(4-Acetamido)phenylpicolinamides as Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4 (mGlu4) with CNS Exposure in Rats
Engers, Darren W.
Field, Julie R.
Le, Uyen
Zhou, Ya
Bolinger, Julie D.
Zamorano, Rocio
Blobaum, Anna L.
Jones, Carrie K.
Jadhav, Satyawan
Weaver, C. David
Conn, P. Jeffrey
Lindsley, Craig W.
Niswender, Colleen M.
Hopkins, Corey R.
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (04) : 1106 - 1110
[7] Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)
Engers, Darren W.
Gentry, Patrick R.
Williams, Richard
Bolinger, Julie D.
Weaver, C. David
Menon, Usha N.
Conn, P. Jeffrey
Lindsley, Craig W.
Niswender, Colleen M.
Hopkins, Corey R.
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (17) : 5175 - 5178
[8] Synthesis and Evaluation of a Series of Heterobiarylamides That Are Centrally Penetrant Metabotropic Glutamate Receptor 4 (mGluR4) Positive Allosteric Modulators (PAMs)
Engers, Darren W.
Niswender, Colleen M.
Weaver, C. David
Jadhav, Satyawan
Menon, Usha N.
Zamorano, Rocio
Conn, P. Jeffrey
Lindsley, Craig W.
Hopkins, Corey R.
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (14) : 4115 - 4118
[9] Engers DW, 2016, ACS CHEM NEUROSCI
[10] Metabotropic Glutamate Receptors as Therapeutic Targets for Cognitive Disorders
Gravius, A.
Pietraszek, M.
Dekundy, A.
Danysz, W.
[J]. CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2010, 10 (02) : 187 - 206

← 1 2 3 →