title: 6-aminoalkyloxazolo[4,5-b]pyridin-2(3H)-ones: synthesis and evaluation of antinoceptive activity.
abstract: Series of 6-aminoalkyloxazolo[4,5-b]pyridin-2(3H)-ones incorporating structural modifications both in the alkyl chain and basic amino moiety were tested for their analgesic efficacy and safety in mice and rats. Two of the synthesised compounds, 4a (3-methyl-6-[(4-phenyl-1-piperazinyl)methyl]oxazolo[4,5-b]pyridin-2(3H)-one) and 12a (3-methyl-6¿1-[2-(4-phenyl-1-piperazinyl)ethan-1-ol]¿oxazolo[4,5-b]pyridin- 2(3H)-one) were found to be more potent than aspirin with ED50 values of 26 (16.1-42.4) and 15.5 (11.4-21.2) mg/kg po (mouse, phenylquinone writhing test) respectively and 6 (3.1-9.8) and 5.5 (3.5-8.8) mg/kg po (rat, acetic acid writhing test). Compounds 4a and 12a proved to be potent nonopioid nonantiinflammatory analgesics but unfortunately have sedative properties at relatively low doses (respectively 64 and 16 mg/kg po, mice).
authors.affiliation: Institut de Chimie Organique et Analytique, associé au CNRS, Université d'Orléans, France.
authors.forename: L
authors.initials: L
authors.lastname: Savelon
authors.forename: J G
authors.initials: JG
authors.lastname: Bizot-Espiard
authors.forename: D H
authors.initials: DH
authors.lastname: Caignard
authors.forename: B
authors.initials: B
authors.lastname: Pfeiffer
authors.forename: P
authors.initials: P
authors.lastname: Renard
authors.forename: M C
authors.initials: MC
authors.lastname: Viaud
authors.forename: G
authors.initials: G
authors.lastname: Guillaumet
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000097:blood; D001921:Brain / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006098:Granulocytes / Q000187:drug effects / Q000201:enzymology; D006168:Guinea Pigs; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010080:Oxazoles; D011728:Pyridones; D011956:Receptors, Cell Surface; D000001:Calcimycin; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases