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Abstract

The invention is directed to methods to inhibit p38-.alpha. kinase using compounds of the formula and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein represents a single or double bond; one Z.sup.2 is CA or CR.sup.8A and the other is CR.sup.1, CR.sup.1.sub.2, NR.sup.6 or N wherein each R.sup.1, R.sup.6 and R.sup.8 is independently hydrogen or noninterfering substituent; A is --W.sub.i--COX.sub.jY wherein Y is COR.sup.2 or an isostere thereof and R.sup.2 is hydrogen or a noninterfering substituent, each of W and X is a spacer of 2-6 .ANG., and each of i and j is independently 0 or 1; Z.sup.3 is NR.sup.7 or O; each R.sup.3 is independently a noninterfering substituent; n is 0-3; each of L.sup.1 and L.sup.2 is a linker; each R.sup.4 is independently a noninterfering substituent; m is 0-4; Z.sup.1 is CR.sup.5 or N wherein R.sup.5 is hydrogen or a noninterfering substituent; each of 1 and k is an integer from 0-2 wherein the sum of 1 and k is 0-3; Ar is an aryl group substituted with 0-5 noninterfering substituents, wherein two noninterfering substituents can form a fused ring; and the distance between the atom of Ar linked to L.sup.2 and the center of the .alpha. ring is 4.5-24 .ANG..

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First Claim