Substituted pyrido[3,2-b]oxazin-3(4H)-ones: synthesis and evaluation of antinociceptive activity.
A new series of N-substituted pyrido[3,2-b]oxazinones has been synthesized, pharmacologically evaluated, and compared with acetyl salicylic acid. The compound with the maximal combination of safety and analgesic efficacy was 4-¿3-[4-(4-fluorophenyl-1-piperazinyl)propyl]¿-2H-pyrido[3,2-b]-1, 4-oxazin-3(4H)-one (6c) with ED50 values of 12.5 mg/kg po (mouse: phenylquinone writhing test) and 27.8 mg/kg po (rat: acetic acid writhing test), respectively. Compound 6c proved to be more active than aspirin with a safety index of 5.1.
Savelon
L
L
Institut de Chimie Organique et Analytique, associé au CNRS, Université d'Orléans, France.
Bizot-Espiard
J G
JG
Caignard
D H
DH
Pfeiffer
B
B
Renard
P
P
Viaud
M C
MC
Guillaumet
G
G
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D002927:Cimetidine / Q000031:analogs & derivatives / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000378:metabolism; D008297:Male; D051379:Mice; D008956:Models, Chemical; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D010078:Oxazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011738:Pyrilamine / Q000378:metabolism; D011759:Pyrrolidines / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D000700:Analgesics; D044482:Benzeneacetamides; D004745:Enkephalins; D006633:Histamine Antagonists; D010078:Oxazines; D011725:Pyridines; D011759:Pyrrolidines; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D002927:Cimetidine; C023990:tiotidine; D011738:Pyrilamine; C045444:U 69593