title: Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4): Part I. Discovery of pyrazolo[3,4-d]pyrimidines as novel mGluR4 positive allosteric modulators.
abstract: This letter describes the synthesis and SAR, developed through an iterative analogue library approach, of an mGluR4 positive allosteric modulator lead based on a pyrazolo[3,4-d]pyrimidine scaffold. Despite tremendous therapeutic potential, Compound 7, VU0080421, and related congeners represent only a handful of mGluR4 positive allosteric modulators ever described.
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, 802 Robinson Research Building, Nashville, TN 37232-6600, USA.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Niswender
authors.forename: Evan P
authors.initials: EP
authors.lastname: Lebois
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Luo
authors.forename: Kwangho
authors.initials: K
authors.lastname: Kim
authors.forename: Hubert
authors.initials: H
authors.lastname: Muchalski
authors.forename: Huiyong
authors.initials: H
authors.lastname: Yin
authors.forename: P Jeffrey
authors.initials: PJ
authors.lastname: Conn
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D016466:CHO Cells; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D018698:Glutamic Acid / Q000737:chemistry; D008956:Models, Chemical; D018377:Neurotransmitter Agents / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry*; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D018377:Neurotransmitter Agents; D011743:Pyrimidines; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; C030986:pyrimidine; C108823:metabotropic glutamate receptor 4
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