Patent Number: 6,251,913

Title: Hydroxamic acids substituted by heterocycles useful for inhibition of tumor necrosis factor

Abstract: Compounds of formula (I), ##STR1## 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.1-8 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkyny, C.sub.3-8 cycloalkyl, aryl, heteroaryl, heterocyclyl, arylC.sub.1-6 alkyl, heteroarylC.sub.1-6 alkyl, heterocyclylC.sub.1-6 alkyl or C.sub.3-8 cycloalkylC.sub.1-6 alkyl; R.sup.2 is C.sub.1-6 alkyl, C.sub.2-6 alkenyl, arylC.sub.1-6 alkyl, heteroarylC.sub.1-6 alkyl or the side-chain of a naturally occurring amino acid; R.sup.3 is hydrogen, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.4-8 cycloalkenyl, arylC.sub.1-6 alkyl, heteroarylC.sub.1-6 alkyl or heterocycylC.sub.1-6 alkyl; R.sup.4 is hydrogen or C.sub.1-6 alkyl; 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 pharmaceutically acceptable salts and in vivo hydrolysable esters thereof, are described as inhibitors of the production of Tumor Necrosis Factor and/or one or more matrix metalloproteinase enzymes. Compositions containing them and their preparation are also described.

Inventors: Bird; Thomas Geoffrey Colerick (Reims, FR)

Assignee: Zeneca Limited

International Classification: C07D 209/38 (20060101); C07D 215/14 (20060101); C07D 239/00 (20060101); C07D 239/90 (20060101); C07D 241/00 (20060101); C07D 209/00 (20060101); C07D 241/42 (20060101); C07D 215/00 (20060101); C07D 265/36 (20060101); C07D 277/00 (20060101); C07D 265/00 (20060101); C07D 263/56 (20060101); C07D 263/00 (20060101); C07D 215/227 (20060101); C07D 277/64 (20060101); A61K 031/470 (); A61K 031/505 (); C07D 215/14 (); C07D 239/90 (); C07D 263/64 ()

Expiration Date: 06/26/2018