Oxime derivatives of indole and indene compounds as inhibitors of prostaglandin biosynthesis

摘要

Described herein are compounds having the formula <IMAGE> or a pharmaceutically acceptable salt thereof wherein L is selected from the group consisting of <IMAGE> R2 is selected from (a) <IMAGE> <IMAGE> (b) <IMAGE> (c) <IMAGE> (d) R3 is selected from optionally substituted phenyl, and optionally substituted pyridyl; Y is selected from halogen, alkyl, haloalkyl, alkoxy, pyridylmethoxy, thiazolylmethoxy, benzothiazolylmethoxy, quinolylmethoxy, and optionally substituted quinolylmethoxy; W is selected from hydrogen, alkyl, hydroxyalkyl, and hydroxy; A is absent or is selected from optionally substituted alkylene optionally substituted cycloalkylene, optionally substituted cycloalkylene wherein one or two of the carbon atoms is replaced with one or two heteroatoms independently selected from O, S, and N, and <IMAGE> and X is absent or is alkylene; Z is selected from (a) hydrogen, (b) COM wherein M is selected from (b-1) a pharmaceutically acceptable metabolically cleavable group, (b-2)-OR10,(b-3)-O(CH2)w-CH(OR12)-CH2OR13, and (b-4)-NR15R16(c)-OR17, (d) tetrazolyl, (e)-CH(OR17)-CH2OR18,(f)-CH(OR17)-CH2-CH2OR18, (g)-CH(OR17)-CH(OR18)-CH2OR19, and (h)=N-OR17; and R1 and R4 selected from (a) hydrogen, (b) alkyl, and (c) optionally substituted phenyl, are prostaglandin biosynthesis inhibitors and are useful in the treatment of inflammatory disease states. Also disclosed are prostaglandin inhibiting compositions, and a method of inhibiting prostaglandin biosynthesis in a mammal.