N-pyridinyl-indole-3-(alkyl)carboxamides and derivatives as potential systemic and topical inflammation inhibitors.

Abstract

N-substituted-(indol-3-yl)carboxamides 10-15 and alkanamides 16-18 were prepared starting from the corresponding acids and submitted to screening for evaluation of their anti-inflammatory activity. None of the considered carboxamides exhibited significant inhibitory effect in the carrageenin-induced rat paw oedema after oral administration of 0.1 mM x kg(-1); nevertheless introduction of an alkyl chain, leading to alkanamides 16-18, induced moderate to high activity: 46-95% inhibition. The efficacy of these compounds in the inhibition of topical inflammation was confirmed by measuring reduction of ear thickness in the acute tetradecanoyl phorbol acetate (TPA)-induced mouse ear swelling assay. Preliminary pharmacomodulation brought to the fore that toxic effects induced, at 0.4 mM x kg(-1), by N-(pyridin-4-yl)(indol-3-yl)propanamide (17) could be attenuated or suppressed by 5-fluorination or introduction of a methoxycarbonylborane moiety, leading to 18 and 21.

• Authors: M Duflos, M R Nourrisson, J Brelet, J Courant, G LeBaut, N Grimaud, J Y Petit
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 36 Issue 6 Pg. 545-53 (Jun 2001) ISSN: 0223-5234 [Print] France
• PMID: 11525845 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Indoles
• Pyridines
• Carrageenan
• Tetradecanoylphorbol Acetate

Topics

• Administration, Topical
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, chemical synthesis, pharmacology, therapeutic use)
• Carrageenan (pharmacology)
• Drug Design
• Drug Evaluation, Preclinical
• Ear, External (drug effects, pathology)
• Edema (chemically induced, drug therapy, pathology)
• Indoles (administration & dosage, chemical synthesis, pharmacology, therapeutic use)
• Inflammation (chemically induced, drug therapy, pathology)
• Magnetic Resonance Spectroscopy
• Male
• Mice
• Pyridines (administration & dosage, chemical synthesis, pharmacology, therapeutic use)
• Rats
• Spectrophotometry, Infrared
• Structure-Activity Relationship
• Tetradecanoylphorbol Acetate (pharmacology)