title: Discovery and characterization of a novel series of N-phenylsulfonyl-1H-pyrrole picolinamides as positive allosteric modulators of the metabotropic glutamate receptor 4 (mGlu4).
abstract: Herein we report the synthesis and characterization of a novel series of N-phenylsulfonyl-1H-pyrrole picolinamides as novel positive allosteric modulators of mGlu4. 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 mGlu4.
authors.affiliation: Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
authors.forename: Rocco D
authors.initials: RD
authors.lastname: Gogliotti
authors.affiliation: Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Blobaum
authors.affiliation: Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Morrison
authors.affiliation: Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
authors.forename: J Scott
authors.initials: JS
authors.lastname: Daniels
authors.affiliation: Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
authors.forename: James M
authors.initials: JM
authors.lastname: Salovich
authors.affiliation: Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
authors.forename: Yiu-Yin
authors.initials: YY
authors.lastname: Cheung
authors.affiliation: Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
authors.forename: Alice L
authors.initials: AL
authors.lastname: Rodriguez
authors.affiliation: Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Loch
authors.affiliation: Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Vanderbilt Kennedy Center, Vanderbilt University, Nashville, TN 37232, United States.
authors.forename: P Jeffrey
authors.initials: PJ
authors.lastname: Conn
authors.affiliation: Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Chemistry, Vanderbilt University, Nashville, TN 37232, United States.
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
authors.affiliation: Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Vanderbilt Kennedy Center, Vanderbilt University, Nashville, TN 37232, United States.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Niswender
authors.affiliation: Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Chemistry, Vanderbilt University, Nashville, TN 37232, United States. Electronic address: corey.r.hopkins@vanderbilt.edu.
authors.forename: Corey R
authors.initials: CR
authors.lastname: Hopkins
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D008862:Microsomes, Liver / Q000378:metabolism; D010848:Picolinic Acids / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology
chemical_list: C000621093:N-(1-((3,4-dimethylphenyl)sulfonyl)-1H-pyrrol-3-yl)picolinamide; D010848:Picolinic Acids; D011758:Pyrroles; D018094:Receptors, Metabotropic Glutamate; D013449:Sulfonamides; D014230:Triazoles; C033020:1-aminobenzotriazole; C108823:metabotropic glutamate receptor 4
keywords: Metabotropic glutamate receptor 4; PK; Phenyl replacement; Positive allosteric modulator (PAM); Pyrrole sulfonamide