Nicotinanilides as inhibitors of neutrophil chemotaxis

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Abstract

A series of 4-fluoronicotinanilides was synthesized and shown to be novel, potent, and selective inhibitors against GRO-α-driven human neutrophil chemotaxis. Compounds of this class may be useful for the treatment of inflammatory, autoimmune, and allergic disorders.

This communication describes the synthesis and SAR of a novel series of substituted nicotinanilides as potent modulators of GRO-α-driven human neutrophil chemotaxis. Compound 5b was a potent inhibitor of chemotaxis (IC50=42 nM) and demonstrated high selectivity over the chemoattractant polypeptide N-formyl-methionyl-leucyl-phenylalanine (IC50>40 μM).

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Acknowledgements

The authors would like to thank Dr. Breda Twomey for performing assays on these compounds and Mr. Ted Baughman and Dr. Scott Jeffrey, for helpful discussions.

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