Synthesis of N-substituted 4,6-dioxo-imidazo[3,4-c] thiazoles and their analgesic activity in mice.
A new series of N-substituted dioxo-imidazo[3,4-c]thiazoles have been prepared and evaluated for their analgesic activity. The structures of these new derivatives were confirmed by lR, 1H NMR and 13C NMR spectra, and by elemental analysis. When administered intraperitoneally to mice all derivatives were devoid of any toxic effect, even at the high dose of 800 mg kg(-1). In the phenylbenzoquinone-induced abdominal constriction test in mice, eight of the nine synthesized compounds exhibited significant antinociceptive properties with ED50 values (50% effective dose) ranging from 46.7 to 104.7 mg kg(-1) intraperitoneally. Further investigation demonstrated that analgesic activity of the most effective derivatives 5e and 5f partly involved opioidergic and/or noradrenergic pathways.
Hugon
B
B
Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, Université d'Auvergne, Clermont-Ferrand, France.
Rubat
C
C
Coudert
P
P
Leal
F
F
Fialip
J
J
Couquelet
J
J
D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000700:Analgesics; D016227:Benzoquinones; D013844:Thiazoles; D015016:Yohimbine; C029322:phenylbenzoquinone