Substituted 5H-dibenz[b,g]-1,4-oxazocines and related amino acids with antiinflammatory activity.
During an investigation of the antiinflammatory properties of a number of tetracyclic derivatives of 6,8-dichlorodibenz[b,f]oxepin-10(11H)-one, the ring-expanded 1,3-dichloro-5H-dibenz[b,g]-1,4-oxazocine (9) was prepared and found to be considerable pharmacological interest. It was subsequently found that the corresponding ring-opened amino acid 66, a close analogue of the antiinflammatory agent fenclofenac, also possessed significant antiinflammatory activity, superior both to the dibenzoxazocine and to fenclofenac. These findings prompted extensive synthetic programs in both areas, and a number of derivatives in the amino acid series showed potencies considerably in excess of the standard compound. These phenylacetic acids, however, were significantly more ulcerogenic than fenclofenac whereas the corresponding dibenzoxazocines showed few signs of ulcerogenicity at doses up to 1 g/kg.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis*; D001169:Arthritis, Experimental / Q000188:drug therapy; D005260:Female; D008297:Male; D010079:Oxazocines / Q000138:chemical synthesis* / Q000627:therapeutic use; D010648:Phenylacetates / Q000138:chemical synthesis* / Q000627:therapeutic use; D051381:Rats; D013270:Stomach / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced
D000893:Anti-Inflammatory Agents; D010079:Oxazocines; D010648:Phenylacetates; C044508:1,3-dichloro-6,7-dihydro-5H-dibenz(b,g)-1,4-oxazocine; C044509:2-(6-amino-2,4-dichlorophenoxy)phenylacetic acid