Hoffmann-la Roche Inc.

Christopher R Self

John M Osbond

Geoffrey Lawton

Peter J Machin

Carey Ernest Smithen

Brian P Tong

Compounds of the formula ##STR1## wherein A taken together with the two carbon atoms denoted as .alpha. and .beta. is a group of the formula ##STR2## and the dotted line is the double bond present in formulas (i) and (iii); and wherein n is zero, 1, 2 or 3, one of R.sup.1 and R.sup.2 is carboxy or alkoxycarbonyl and the other is hydrogen, R.sup.3 is hydrogen, alkyl, alkoxy, aryloxy, azido, cyano or alkylthio, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 each, independently, is hydrogen or alkyl or, when R.sup.1 is carboxy or alkoxycarbonyl and n stands for 1, R.sup.4 and R.sup.6 taken together can be a carbon-carbon bond or, when R.sup.2 is carboxy or alkoxycarbonyl, R.sup.5 and R.sup.7 taken together can be a carbon-carbon bond, R.sup.8 is halogen, alkyl, haloalkyl or alkoxy and R.sup.9 is hydrogen, halogen, alkyl or alkoxy, and pharmaceutically acceptable salts of the compounds of formula I in which one of R.sup.1 and R.sup.2 is carboxy and the other is hydrogen with bases, can be used as medicaments for the treatment of rheumatoid arthritis, inflammatory respiratory diseases, inflammatory bowel disease, shock and inflammation associated with ischemia. The compounds of formula I can be prepared according to methods hereinafter described.

Substituted isoxazole derivatives

Oxazole and isoxazole derivatives of the formula ##STR1## wherein A is C.sub.1-6 -alkylene, Het is a 2-R-oxazol-5-yl, 5-R-oxazol-2-yl, 4-R-oxazol-2-yl, 2-R-oxazol-4-yl, 3-R-isoxazol-5-yl or 5-R-isoxazol-3-yl group which is optionally substituted on the heterocyclic ring by a C.sub.1-6 -alkyl group, R is phenyl or thienyl monosubstituted or disubstituted by halogen, trifluoromethyl or C.sub.1-6 -alkylthio, R.sup.1 and R.sup.2 each is a C.sub.1-6 -alkyl group and R.sup.3 is a hydroxy or C.sub.1-6 -alkoxy group or a group of the formula --NR.sup.4 R.sup.5 in which R.sup.4 and R.sup.5 each is a hydrogen atom or a C.sub.1-6 -alkyl group or R.sup.4 and R.sup.5 together with the nitrogen atom to which they are attached is a 5-membered or 6-membered saturated heteromonocyclic ring which may contain an oxygen or sulphur atom or an additional nitrogen atom, and pharmaceutically acceptable salts of the compounds of formula I in which R.sup.3 is a hydroxy group with bases, have anti-arthritic activity.

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Christopher R Self