Abstract
The new compound 1-(2-chloro-6-fluorophenyl)-5-methylindolin-2-one (1), designed using the prodrug approach, was easily obtained in 85% yield and characterized by nuclear magnetic resonance, elemental analysis, mass spectrometry and infrared spectroscopy. The lactam 1 showed anti-inflammatory and analgesic activity comparable to that of the COX-2 inhibitor lumiracoxib, without gastro-ulceration effects. Stability studies demonstrated that the lactam function was stable and did not hydrolyze in pH 1.2 or 7.4. Furthermore, using a thioglycollate-induced peritonitis model, compound 1 was shown to inhibit cell migration by 50.4%, while lumiracoxib inhibited it by 18%. This compound represents a new non-ulcerogenic prototype for the treatment of chronic inflammatory diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesics / pharmacology
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Animals
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Anti-Inflammatory Agents / adverse effects
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Anti-Inflammatory Agents / chemical synthesis*
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Anti-Inflammatory Agents / pharmacology*
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Cell Movement / drug effects
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Cyclooxygenase 2 Inhibitors / adverse effects
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Cyclooxygenase 2 Inhibitors / chemical synthesis
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Diclofenac / adverse effects
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Diclofenac / analogs & derivatives
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Diclofenac / pharmacology
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Drug Stability
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Female
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Gastric Mucosa / drug effects*
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Hydrogen-Ion Concentration
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Indoles / pharmacology*
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Indomethacin / adverse effects
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Indomethacin / pharmacology
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Lactams / adverse effects
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Lactams / chemical synthesis*
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Lactams / pharmacology*
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Male
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Mice
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Prodrugs / adverse effects
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Prodrugs / chemical synthesis
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Prodrugs / pharmacology
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Rats
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Rats, Wistar
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Stomach Ulcer / chemically induced
Substances
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1-(2-chloro-6-fluorophenyl)-5-methylindolin-2-one
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Analgesics
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Anti-Inflammatory Agents
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Cyclooxygenase 2 Inhibitors
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Indoles
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Lactams
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Prodrugs
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Diclofenac
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lumiracoxib
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Indomethacin