Quinazoline derivatives as medicaments

A pharmaceutical composition for treating conditions characterized by enhanced p38-α activity and/or enhanced TGF-β activity which composition comprises a therapeutically effective amount of a compound of the formula

• 22
• or the pharmaceutically acceptable salts thereof
• wherein R3 is a noninterfering substituent;
• each Z is CR2 or N, wherein no more than two Z positions in ring A are N, and wherein two adjacent Z positions in ring A cannot be N;
• each R2 is independently a noninterfering substituent;
• L is a linker;
• n is 0 or 1;
• and
• Ar′ is the residue of a cyclic aliphatic, cyclic heteroaliphatic, aromatic or heteroaromatic moiety optionally substituted with 1-3 noninterfering substituents in admixture with at least one pharmaceutically acceptable excipient.

A compound of the formula:

• 23
• and the pharmaceutically acceptable salts thereof
• wherein each R2 is independently a noninterfering substituent;
• m is an integer of 0-4;
• Z is CH;
• R1 is alkyl (1-6C) or arylalkyl optionally substituted on the aryl group with 1-3 substituents independently selected from alkyl (1-6C), halo, OR, NR2, SR, —OOCR, —NROCR, RCO, —COOR, —CONR2, —SO2NR2, CN, CF3, and NO2, wherein each R is independently H or lower alkyl (1-4C);
• n is 0, 1 or 2;
• and
• (a) Ar is phenyl, substituted with at least one group selected from the group consisting of optionally substituted alkyl (1-6C), halo, OR, NR2, SR, —OOCR, —NROCR, RCO, —COOR, —CONR2, SO2NR2, CN, CF3, and NO2, wherein each R is independently H or lower alkyl (1-4C), or pyridyl, indolyl, or pyrimidyl, each optionally substituted with at least one group selected from the group consisting of optionally substituted alkyl (1 -6C), halo, OR, NR2, SR, -OOCR, —NROCR, RCO, —COOR, —CONR2, SO2NR2, CN, CF3, and NO2, wherein each R is independently H or lower alkyl (1-4C);
• and
• R3 is a branched or cyclic alkyl group (5-7C) or is phenyl optionally substituted with 1-2 substituents which substituents are selected from the group consisting of alkyl (1-6C), halo, OR, NR2, SR, —OOCR, —NROCR, RCO, —COOR, —CONR2, —SO2NR2, CN, CF3, and NO2, wherein each R is independently H or lower alkyl (1-4C);
• or
• (b) Ar is phenyl, pyridyl, indolyl, or pyrimidyl, each optionally substituted with a group selected from the group consisting of optionally substituted alkyl (1-6C), halo, OR, NR2, SR, —OOCR, —NROCR, RCO, —COOR, —CONR2, SO2NR2, CN, CF3, and NO2, wherein each R is independently H or lower alkyl (1-4C);
• and R3 is a branched or cyclic alkyl group (5-7C) or is phenyl substituted with 1-2 substituents which substituents are selected from the group consisting of alkyl (1-6C), halo, SR, —OOCR, —NROCR, RCO, —COOR, —CONR2, —SO2NR2, CN, and CF3, wherein each R is independently H or lower alkyl (1C);
• or
• (c) Ar is phenyl substituted with a group selected from the group consisting of optionally substituted NR2, SR, —NROCR, RCO, —CONR2, SO2NR2, CN, and CF3, wherein each R is independently H or lower alkyl (1-4C);
• or pyridyl substituted with a group selected from the group consisting of optionally substituted alkyl (1-6C), halo, OR, NR2, SR, —OOCR, —NROCR, RCO, —COOR, —CONR2, SO2NR2, CN, CF3, and NO2, wherein each R is independently H or lower alkyl (14C);
• or indolyl or pyrimidyl, each optionally substituted with a group selected from the group consisting of optionally substituted alkyl (1-6C), halo, OR, NR2, SR, —OOCR, —NROCR, RCO, —COOR, —CONR2, SO2NR2, CN, CF3, and NO2, wherein each R is independently H or lower alkyl (1-4C);
• and
• R3 is a branched or cyclic alkyl group (5-7C) or is phenyl optionally substituted with 1-2 substituents which substituents are selected from the group consisting of alkyl (1-6C), halo, OR, NR2, SR, -OOCR, —NROCR, RCO, —COOR, —CONR2, —SO2NR2, CN, CF3, and NO2, wherein each R is independently H or lower alkyl (1-4C);
• or
• (d) Ar is phenyl, pyridyl, indolyl, or pyrimidyl, each optionally substituted with a group selected from the group consisting of optionally substituted alkyl (1-6C), halo, OR, NR2, SR, —OOCR, —NROCR, RCO, —COOR, —CONR2, SO2NR2, CN, CF3, and NO2, wherein each R is independently H or lower alkyl (1-4C);
• and
• R3 is a branched or cyclic alkyl group (5-7C) or is phenyl substituted with 1-2 substituents which substituents are selected from the group consisting of alkyl (1-6C), halo, OR, SR, —OOCR, —NROCR, RCO, —COOR, —CONR2, —SO2NR2, CN, CF3, and NO2, wherein each R is independently H or lower alkyl (1-4C).