The discovery of anthranilic acid-based MMP inhibitors. Part 1: SAR of the 3-position

• Published in: Bioorganic & medicinal chemistry letters Vol. 11; no. 2; pp. 235 - 238
• Main Authors: LEVIN, Jeremy I, DU, Mila T, GUIXIAN JIN, COWLING, Rebecca, SKOTNICKI, Jerauld S, DIJOSEPH, John F, KILLAR, Loran M, SUNG, Amy, WALTER, Thomas, SHARR, Michele A, ROTH, Catherine E, MOY, Franklin J, POWERS, Robert
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 22.01.2001
• Subjects: Animals; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Combinatorial Chemistry Techniques; Humans; Hydroxamic Acids - chemical synthesis; Hydroxamic Acids - chemistry; Hydroxamic Acids - pharmacology; Inhibitory Concentration 50; Matrix Metalloproteinase 13; Matrix Metalloproteinase Inhibitors; Medical sciences; ortho-Aminobenzoates - chemical synthesis; ortho-Aminobenzoates - chemistry; ortho-Aminobenzoates - pharmacology; Pharmacology. Drug treatments; Protease Inhibitors - chemical synthesis; Protease Inhibitors - chemistry; Protease Inhibitors - pharmacology; Structure-Activity Relationship; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Sulfonamides - pharmacology; Rat; Nitrogen heterocycle; Metalloendopeptidases; Pyridine derivatives; Structure activity relation; Six membered ring; Chemical synthesis; Interstitial collagenase; Sulfonamide; Enzyme; Rodentia; Oral administration; Hydroxamic acid; Enzyme inhibitor; In vitro; Gelatinase B; Peptidases; In vivo; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Hydrolases; Benzenic compound
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(00)00642-9

A novel series of anthranilic acid-based inhibitors of MMP-1, MMP-9, and MMP-13 was prepared and evaluated both in vitro and in vivo. The most potent compound, 6e, has in vivo activity in a rat sponge-wrapped cartilage model.