Tetrahydroisoquinoline based sulfonamide hydroxamates as potent matrix metalloproteinase inhibitors

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 1; pp. 47 - 50
• Main Authors: Ma, Dawei, Wu, Wengen, Yang, Guoxin, Li, Jingya, Li, Jia, Ye, Qizhuang
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 05.01.2004; Elsevier
• Subjects: Biological and medical sciences; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Hydroxamic Acids - chemistry; Hydroxamic Acids - pharmacology; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases - metabolism; Medical sciences; Miscellaneous; MMP inhibitors; Pharmacology. Drug treatments; Sulfonamides - chemistry; Sulfonamides - pharmacology; Synthesis; Tetrahydroisoquinolines - chemistry; Tetrahydroisoquinolines - pharmacology; MMP inhibitors; Synthesis; Isoquinoline derivatives; Sulfonamide; Enzyme; Nitrogen heterocycle; Hydroxamic acid; Enzyme inhibitor; Metalloendopeptidases; In vitro; Peptidases; Structure activity relation; Bicyclic compound; Hydrolases; Aromatic compound; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2003.10.026

The synthesis and MMP inhibitory activity of a series of tetrahydroisoquinoline based sulfonamide hydroxamates are described. In nine MMPs tested, most of the compounds display potent inhibition activity except for MMP-7. Some subtle isozyme selectivity is observed by varying the substituents at the 6- and 7-positions and aromatic ring of arylsulfonyl groups. Graphic