INDOLE-TYPE DERIVATIVES AS INHIBITORS OF P38 KINASE

摘要

The invention is directed to methods to inhibit p38-.alpha. kinase using compounds of formula (1), and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein (a) represents a single or double bond; one Z2 is CA or CR8A and the other is CR1, CR12, NR6 or N where in each R1, R6 and R8 is independently hydrogen or noninterfering substituent; A is -Wi-COXjY wherein Y is COR2 or an isostere thereof and R2 is hydrogen or a noninterfering substituent, each of W and X is a spacer of 2-6.ANG., and eac h of i and j is independently 0 or 1; Z3 is NR7 or O; each R3 is independently a noninterfering substituent; n is 0-3; each of L1 and L2 is a linker; each R4 is independently a noninterfering substituent; m is 0-4; Z1 is CR5 or N wherein R5 is hydrogen or a noninterfering substituent; each of l and k is a n integer from 0-2 wherein the sum of l 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 L2 and the center of the .alpha. ring is 4.5-24.ANG..