Analgesic activity of novel spiro heterocycles. 2-Amino-7-oxa-3-thia-1-azaspiro[5,5]undec-1-enes and related compounds.
(+/-)-2-Amino-7-oxa-3-thia-1-azaspiro[5,5]undec-1-ene (1a) and many of its derivatives exhibit significant activity in the phenylquinone writhing and yeast inflamed foot assays. In order to develop structure-activity relationships, the related spiroheterocycles, (+/-)-2-amino-7-oxa-3-thia-1-azaspiro[5,4]dec-1-ene (2), (+/-)-2-amino-3-thia-1-azaspiro[5,5]undec-1-ene (3), and (+/-)-2-amino-7-oxa-1-azaspiro[5,5]undec-1-ene (4), were examined. Of these, only 4 failed to show activity indicating that the analgetic properties displayed by compounds 1--3 are associated, mainly, with the 2-amino-1,3-thiazine ring system. In the 2-acylimino series, evidence is presented suggesting a contribution to the observed activity on the part of the spiroannulated ether ring as well. Both 1a and its p-fluorobenzoyl derivative 33 exhibit analgesic activity in the rat tail-flick assay.
D000700:Analgesics / Q000138:chemical synthesis* / Q000633:toxicity; D000818:Animals; D005260:Female; D007249:Inflammation / Q000503:physiopathology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D011809:Quinones / Q000037:antagonists & inhibitors; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship
D000700:Analgesics; D011809:Quinones; D013141:Spiro Compounds