Novel nonopioid non-antiinflammatory analgesics: 3-(aminoalkyl)- and 3-[(4-aryl-1-piperazinyl)alkyl]oxazolo[4,5-b]pyridin-2(3H)-ones.
A series of 3-(aminoalkyl)- and 3-[(4-aryl-1-piperazinyl)alkyl]oxazolo[4,5-b]pyridin-2(3H)-ones were prepared from their respective oxazolo[4,5-b]pyridin-2(3H)-ones. Several members of this group were found to possess potent analgesic activity in the mouse during a p-phenylquinone writhing induced test. Among them, phenylpiperazine compounds with two-carbon length alkyl chains, 2a and 2b, appeared by high analgesic with little toxicity having neither an antiinflammatory effect nor opioid receptor affinity. The synthesis and structure-affinity relationships for this series are detailed.
Flouzat
C
C
Laboratoire de Chimie Bioorganique et Analytique, Université d'Orléans, France.
Bresson
Y
Y
Mattio
A
A
Bonnet
J
J
Guillaumet
G
G
D000595:Amino Acid Sequence; D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000633:toxicity; D016227:Benzoquinones; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis* / Q000633:toxicity; D010147:Pain Measurement; D011728:Pyridones / Q000138:chemical synthesis* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism; D013329:Structure-Activity Relationship
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D010080:Oxazoles; D011728:Pyridones; D011957:Receptors, Opioid; C088312:S 12813; C080799:3-(2-(4-(3-(trifluoromethyl)phenyl)-1-piperazinyl)ethyl)oxazolo(4,5-b)pyridin-2(3H)-one; C029322:phenylbenzoquinone