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.
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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)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Indoles
- Pyridines
- Carrageenan
- Tetradecanoylphorbol Acetate
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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)
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