Abstract
We describe here the discovery and the structure-activity relationship (SAR) of a series of 4-(1-Aryltriazol-4-yl)-tetrahydropyridines as novel mGluR1 antagonists. Our extensive chemical modification of lead compound 2 successfully led to fluoropyridine analogs 7j and 1 with improved in vivo antagonistic activities. Among the evaluated compounds, chemically stable urea analog 1 showed oral antagonistic activity at dose ranges of 10-30mg/kg in an animal model.
MeSH terms
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Administration, Oral
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Animals
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CHO Cells
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Cricetinae
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Cricetulus
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Humans
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Inhibitory Concentration 50
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Mice
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Microsomes, Liver / metabolism
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Pyridines / chemical synthesis
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Pyridines / chemistry*
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Pyridines / pharmacology*
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Rats
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Receptors, Metabotropic Glutamate / antagonists & inhibitors*
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Receptors, Metabotropic Glutamate / metabolism
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Structure-Activity Relationship
Substances
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Pyridines
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Receptors, Metabotropic Glutamate
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metabotropic glutamate receptor type 1