| abstract |
The invention is directed to methods to inhibit p38-α kinase using compounds of formula (I) and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein ---- represents a single or double bond; B 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 A, and each of i and j is independently 0 or 1; each R3 is independently a noninterfering substituent, wherein n is 0-3; Z?3 is NR7¿ or O; wherein R7 is H or a noninterfering substituent; one Z2 is C or CR8A and the other is CR1, CR12, NR6 or N wherein each R?1, R6 and R8¿ is independently hydrogen or noninterfering substituent; wherein A is (II) such that Z?1 is CR5¿ or N wherein R5 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; each R4 is independently a noninterfering substituent where m is 0-4; each of L?1 and L2¿ is a linker; and the distance between the atom of Ar linked to L2 and the center of the β ring is a 4.5-24A. |