Nicotinanilides as inhibitors of neutrophil chemotaxis

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...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2002-06, Vol.12 (11), p.1517-1520
Main Authors: Cutshall, Neil S., Kucera, Kristin A., Ursino, Rocky, Latham, John, Ihle, Nathan C.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Bones, joints and connective tissue. Antiinflammatory agents
Chemotaxis, Leukocyte - drug effects
Humans
Inhibitory Concentration 50
Ligands
Medical sciences
Neutrophils - drug effects
Nicotinic Acids - chemical synthesis
Nicotinic Acids - chemistry
Nicotinic Acids - pharmacology
Pharmacology. Drug treatments
Structure-Activity Relationship
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Summary: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 (IC 50=42 nM) and demonstrated high selectivity over the chemoattractant polypeptide N-formyl-methionyl-leucyl-phenylalanine (IC 50>40 μM).
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(02)00188-9