Hydroxamic acids substituted by heterocycles useful for inhibition of tumor necrosis factor
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United States of America Patent
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app pub date -
Mar 22, 2001
filing date -
Mar 28, 1997
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Abstract
1Compounds of formula (I), wherein: n is 1 to 6; Het is a nitrogen containing ring fused to the benzene ring on two adjacent carbon atoms to form a bicyclic ring system which ring system may be optionally substituted; R.sup.1 is hydrogen, C.sub.1-8alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.3-8cycloalkyl, aryl, heteroaryl, heterocyclyl, arylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, heterocyclylC.sub.1-6alkyl or C.sub.3-8cycloalkylC.sub.1-6alkyl; R.sup.2 is C.sub.1-6alkyl, C.sub.2-6alkenyl, arylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl or the side-chain of a naturally occurring amino acid; R.sup.3 is hydrogen, C.sub.1-6alkyl, C.sub.3-8cycloalkyl, C.sub.4-8cycloalkenyl, arylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl or heterocyclylC.sub.1-6alky-l; R.sup.4 is hydrogen or C.sub.1-6alkyl; or R.sup.3 and R.sup.4 together with the nitrogen atom to which they are joined form a heterocyclic ring; wherein any group or ring, in R.sup.1-R.sup.4, is optionally substituted; and pharmceutically acceptable salts and in vivo hydrolysable esters thereof, are described as inhibitors of the production of Tumour Necrosis Factor and/or one or more matrix metalloproteinase enzymes. Compositions containing them and their preparation are also described.
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