Abstract
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.
MeSH terms
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Analgesics / chemical synthesis*
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Analgesics / pharmacology
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Animals
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Benzeneacetamides*
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Cimetidine / analogs & derivatives
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Cimetidine / metabolism
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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Enkephalins / metabolism
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Guinea Pigs
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Histamine Antagonists / metabolism
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Male
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Mice
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Models, Chemical
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Nociceptors / drug effects*
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Nociceptors / metabolism
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Oxazines / chemical synthesis*
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Oxazines / pharmacology
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Pyridines / chemical synthesis*
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Pyridines / pharmacology
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Pyrilamine / metabolism
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Pyrrolidines / metabolism
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Receptors, Opioid / drug effects
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Receptors, Opioid / metabolism
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Structure-Activity Relationship
Substances
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Analgesics
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Benzeneacetamides
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Enkephalins
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Histamine Antagonists
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Oxazines
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Pyridines
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Pyrrolidines
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Receptors, Opioid
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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Cimetidine
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tiotidine
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Pyrilamine
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U 69593