A novel synthesis of Rhein (2), the active metabolite of the anti-osteoarthritic drug Diacetyl Rhein (1) has been acehived. Key steps include stereospecific olefination of aldehyde 21 with novel phosphonate 28 and the cyclisation of acid 31 to produce anthracene 32.

A series of 5-acyl-3-substituted-benzofuran-2(3H)-ones and their respective ring-opened o-hydroxy acids were synthesized. The antiinflammatory activity was evaluated in terms of their ability to improve adjuvant induced arthritis in rats. Their effect on the production of both cyclooxygenase (CO) and lipoxygenase (LO) metabolites of arachidonic acid in guinea pig peritoneal polymorphonuclear neutrophils (PMNs) was also examined. No correlation between the antiinflammatory activity and increasing stability of the lactones could be found. The degree of activity in general shown by the benzofuranones was similar to that of their corresponding o-hydroxy acids. This, coupled with the evidence from studies on opening of the lactone ring, suggests an in vivo transformation of the former into the latter. Benzofuranones displayed a dual inhibition of CO and LO products, while a moderate reduction in CO metabolites was shown by their acids.

The synthesis of the 4H-thieno-[2,3-b][1,5]-, -[3,2-b][1,5]-, and -[3,4-b][1,5]-benzodiazepinone ring systems is described. Sodium methylsulphinylmethanide was used for the intramolecular cyclisation of the intermediate amino-esters (5), (9), and (14). However, attempted cyclisation of ethyl 2-(2-amino-4-fluoroanilino)-5-ethyl-thiophen-3-carboxylate (5b) with sodium hydride at a higher temperature caused rearrangement to a benzimidazolone (12).

Bei Zugabe der auf ‐20 bis ‐40°C gekühlten lithiierten Aminoester (II) zu einer Lösung der Benzole (I) in THF bei 20‐40°C entstehen die Verbindungen (III).

The synthesis and antiinflammatory activity of 5-substituted 2-arylbenzoxazoles are described. Initial screening on carrageenin-induced rat paw edema showed that alpha-methylacetic substitution in the 5 position was preferable to substitutions with the equivalent esters, amides, alcohols, amines or tetrazoles. Halogen substitution in the aryl ring led to the most active compounds which were 2-(4-chlorophenyl)-alpha-methyl-5-benzoxazoleacetic acid (14) and 2-(4-fluorophenyl)-alpha-methyl-5-benzoxazoleacetic acid (29). These compounds were three to five times more active than phenylbutazone as assessed from ED30 values determined on rat paw edema 5 hr after single oral doses.