| 摘要 |
The invention is directed to inhibition of p38- alpha kinase using compounds of the formula (1) and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein: Ar<1> is an aryl group substituted with 0-5 non-interfering substituents, wherein two adjacent noninterfering substituents can form a fused aromatic or nonaromatic ring; L<1> and L<2> are linkers; each R<1> is independently a noninterfering substitutent; Z<1> is CR<2> or N wherein R<2> is hydrogen or a noninterfering substituent; m is 0-4; each of n and p is an integer from 0-2 wherein the some of n and p is 0-3; Ar<2> is a substantially planar, monocyclic or polycyclic aromatic moiety having one or more optional ring heteroatoms, said moiety being optionally substituted with one or more optional ring heteroatoms, said moiety being optionally substituted with one or more non-interfering substituents, two or more of which may form a fused ring; Z is W1-COXjY wherein Y is COR<3> or an isotere thereof; R<3> is a noninterfering substituent, each of W and X is a spacer of 2-6 ANGSTROM , and each of i and j is independently 0 or 1; wherein the smallest number of covalent bonds is the compound separating the atom of Ar<1> bonded to L<2> to the atom of Ar<2> bonded to L<1> is at least 6, where each of said bonds has a bond length of 1.2 to 2.0 angstroms; and/or wherein the distance in space between the atom of Ar<1> bonded to L<2> and the atom of Ar<2> bonded to L<1> is 4.5-24 angstroms; with the proviso that the protion of the compound represented by Ar<2>-Z is not formula (2) wherein formula (3) represents a singel or double bond; n is 0-3; one Z<2> is CA or CRA and the other is CR, CR2, NR or N; A is Wi-COXjY wherein Y is COR or an isostere thereof, each of W and X is a spacer of 2-6 ANGSTROM , and each of i and j is independently 0 ot 1; Z<3> is NR or O; and each R independently hydrogen or a mominterfering substituent. |
