Abstract
A general way of improving the potency of CXCR3 antagonists with fused hetero-bicyclic cores was identified. Optimization efforts led to the discovery of a series of imidazo-pyrazine derivatives with improved pharmacokinetic properties in addition to increased potency. The efficacy of the lead compound 21 is evaluated in a mouse lung inflammation model.
MeSH terms
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Animals
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Anti-Inflammatory Agents / chemical synthesis
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Anti-Inflammatory Agents / chemistry*
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Anti-Inflammatory Agents / pharmacokinetics
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Benzeneacetamides / chemical synthesis
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Benzeneacetamides / chemistry*
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Benzeneacetamides / pharmacokinetics
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Cyclic S-Oxides / chemical synthesis
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Cyclic S-Oxides / chemistry*
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Cyclic S-Oxides / pharmacokinetics
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / chemistry*
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Imidazoles / pharmacokinetics
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Mice
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Molecular Conformation
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Pyrazines / chemical synthesis
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Pyrazines / chemistry*
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Pyrazines / pharmacokinetics
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Rats
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Receptors, CXCR3 / antagonists & inhibitors*
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Receptors, CXCR3 / metabolism
Substances
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Anti-Inflammatory Agents
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Benzeneacetamides
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Cyclic S-Oxides
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Imidazoles
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Pyrazines
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Receptors, CXCR3