4-Arylamino, 4-aryloxy, and 4-arylthio diarylamines and derivatives thereof as selective MEK inhibitors

A compound having the formula (II):

• W is OR1, NR2OR1, NRARB, NR2NRARB, or NR2(CH2)2-4 NRARB;
• R1 is H, C1-8 alkyl, C3-8 alkenyl, C3-8 alkynyl, C3-8 cycloalkyl, phenyl, (phenyl)C1-4 alkyl, (phenyl)C3-4 alkenyl, (phenyl)C3-4 alkynyl, (C3-8 cycloalkyl)-C1-4 alkyl, (C3-8 cycloalkyl)C3-4 alkenyl, (C3-8 cycloalkyl)C3-4 alkynyl, C3-8 heterocyclic radical, (C3-8 heterocyclic radical)C1-4 alkyl, (C3-8 heterocyclic radical)C3-4 alkenyl, (C3-8 heterocyclic radical)C3-4 alkynyl or (CH2)2-4NRARB;
• R2 is H, phenyl, C1-4 alkyl, C3-4 alkenyl, C3-8 alkynyl, C3-8 cycloalkyl, or (C3-8 cycloalkyl)-C1-4 alkyl;
• RA is H, C1-6 alkyl, C3-8 alkenyl, C3-8 alkynyl, C3-8 cycloalkyl, phenyl, (C3-8 cycloalkyl)C1-4 alkyl, (C3-8 cycloalkyl)C3-4 alkenyl, (C3-8 cycloalkyl)C3-4 alkynyl, C3-8 heterocyclic radical, (C3-8 heterocyclic radical)C1-4 alkyl, (aminosulfonyl)phenyl, [(aminosulfonyl)phenyl]C1-4 alkyl, (aminosulfonyl)C1-6 alkyl, (aminosulfonyl)C3-6 cycloalkyl, or [(aminosulfonyl)C3-6 cycloalkyl]C1-4 alkyl;
• RB is H, C1-8 alkyl, C3-8 alkenyl, C3-8 alkynyl, C3-8 cycloalkyl, or C6-8 aryl;
• R3 is halo, NO2, SO2NRI(CH2)2-4NRERF, SO2NRIRK or (CO)T;
• T is C1-8 alkyl, C3-8 cycloalkyl, (NRERF)C1-4 alkyl, ORF, NRI(CH2)2-4NRERF, or NRERF;
• R4 is H or F;
• R5 is H, methyl, halo, or NO2;
• R6 is H, methyl, halo, or NO2;
• Ar is phenyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl;
• each of R7 and R8 is independently selected from H, halo, C1-4 alkyl, SO2NRJ (CH2)2-4NRGRH, (CO)(CH2)2-4NRGRH, (CO)NRJ(CH2)2-4NRGRH, (CO)O(CH2)2-4NRGRH, SO2NRGRH, and (CO)NRGRH;
• provided that where Ar is a pyridyl, each of R7 and R8 is H;
• each of RC, RD, RE, RF, RG, and RH is independently selected from H, C1-4 alkyl, C3-4 alkenyl, C3-4 alkynyl, C3-6 cycloalkyl, and phenyl;
• each of NRCRD, NRERF, and NRGRHcan also be independently morpholinyl, piperazinyl, pyrrolidinyl, or piperadinyl;
• each of RI and RJ is independently H, methyl, or ethyl;
• RK is C1-4 alkyl, C3-4 alkenyl, C3-4 alkynyl, C3-6 cycloalkyl, or phenyl;
• X is O, S, or NH;
• and
• wherein each hydrocarbon radical or heterocyclic radical above is optionally substituted with between 1 and 3 substituents independently selected from halo, C1-4 alkyl, C3-6 cycloalkyl, C2-4 alkenyl, C2-4 alkynyl, phenyl, hydroxyl, amino, (amino)sulfonyl, and NO2, wherein each substituent alkyl, cycloalkyl, alkenyl, alkynyl or phenyl is in turn optionally substituted with between 1 and 2 substituents independently selected from halo, C1-2 alkyl, hydroxyl, amino, and NO2;
• or a pharmaceutically acceptable salt or C1-7 ester thereof.