Abstract
A series of novel mGluR1 antagonists have been prepared. Incorporation of fragments derived from weak lead matter into a library led to enhanced potency in a new chemical series. A chemistry driven second library iteration, covering a greatly enhanced area of chemical space, maintained good potency and introduced metabolic stability.
MeSH terms
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Animals
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Binding, Competitive / drug effects
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CHO Cells
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Chemical Phenomena
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Chemistry, Physical
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Chronic Disease
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Cricetinae
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Cricetulus
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Dose-Response Relationship, Drug
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Glutamic Acid / pharmacology
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Pain / drug therapy*
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Pyrazines / chemical synthesis
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Pyrazines / pharmacology
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Rats
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Receptors, Metabotropic Glutamate / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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Pyrazines
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Receptors, Metabotropic Glutamate
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metabotropic glutamate receptor type 1
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Glutamic Acid