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.
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.
Niswender
Colleen M
CM
Department of Pharmacology, Vanderbilt University Medical Center, 802 Robinson Research Building, Nashville, TN 37232-6600, USA.
Lebois
Evan P
EP
Luo
Qingwei
Q
Kim
Kwangho
K
Muchalski
Hubert
H
Yin
Huiyong
H
Conn
P Jeffrey
PJ
Lindsley
Craig W
CW
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
D018377:Neurotransmitter Agents; D011743:Pyrimidines; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; C030986:pyrimidine; C108823:metabotropic glutamate receptor 4
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