Synthesis and structure–Activity relationship of 2-amino-3-heteroaryl-quinoxalines as non-peptide, small-Molecule antagonists for interleukin-8 receptor

• Published in: Bioorganic & medicinal chemistry Vol. 11; no. 17; pp. 3777 - 3790
• Main Authors: Li, Jie Jack, Carson, Kenneth G, Trivedi, Bharat K, Yue, Wen Song, Ye, Qing, Glynn, Roberta A, Miller, Steven R, Connor, David T, Roth, Bruce D, Luly, Jay R, Low, Joseph E, Heilig, David J, Yang, Weixing, Qin, Shixin, Hunt, Stephen
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.08.2003; Elsevier Science
• Subjects: Anti-Inflammatory Agents - chemistry; Antineoplastic Agents - chemistry; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Calcium - metabolism; Chemotaxis - drug effects; Diamines - chemical synthesis; Diamines - chemistry; Diamines - pharmacology; Humans; Medical sciences; Pharmacology. Drug treatments; Quinoxalines - chemical synthesis; Quinoxalines - chemistry; Quinoxalines - pharmacology; Receptors, Interleukin-8A - antagonists & inhibitors; Receptors, Interleukin-8A - metabolism; Structure-Activity Relationship; Quinoxaline derivatives; Nitrogen heterocycle; Non peptide compound; Oxygen heterocycle; In vitro; CXC chemokine receptor; Thiophene derivatives; Sulfur heterocycle; Structure activity relation; Chlorine Organic compounds; Bicyclic compound; Aromatic compound; Antagonist; Benzofuran derivatives; Chemical synthesis; Interleukin 8
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(03)00399-7

Interleukin-8 modulation is implicated in many inflammatory and cancer diseases. Starting from a mass-screening hit, the synthesis and structure–activity relationship of 2-amino-3-heteroarylquinoxalines as non-peptide, small molecule interleukine-8 receptor antagonists have been developed. The optimized derivatives, PD 0210293 ( 13y) and PD 0220245 ( 13r), show inhibition of both IL-8 receptor binding and IL-8-mediated neutrophil chemotaxis. Graphic