Synthesis and pharmacological evaluation of (indol-3-yl)alkylamides as potent analgesic agents.
A series of (indol-3-yl)alkylamides was synthesized and evaluated for analgesic activity. Two N-(pyridin-4-yl)acetamides, compounds 24 and 25, bearing benzyl or 4-fluorobenzyl moieties in 1-position of indole ring exhibited promising analgesic properties (ED50 = 8.1 and 11 mg/kg p.o., respectively), being as potent as the reference drugs flupirtine (CAS 56995-20-1), ibuprofen (CAS 15687-27-1) and diclofenac (CAS 15307-86-5). The two test compounds were tested for their anti-inflammatory activity by carrageenin-induced edema in rat paw test. 4-Fluorobenzyl derivative 25 whose ID50 was 0.085 +/- 0.021 mmol/kg was selected as a lead compound for further pharmacomodulation.
Fouchard
F
F
Laboratoires de Chimie Organique et de Chimie Thérapeutique, Faculté de Pharmacie, Nantes, France.
Marchand
P
P
Le Baut
G
G
Emig
P
P
Nickel
B
B
D000473:Alkanes / Q000138:chemical synthesis* / Q000494:pharmacology; D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D013055:Spectrophotometry, Infrared
D000473:Alkanes; D000577:Amides; D018712:Analgesics, Non-Narcotic; D007202:Indicators and Reagents; D002351:Carrageenan