Potent dual brd4-kinase inhibitors as cancer therapeutics

A compound having Formula III:

• wherein
• X is N or CH;
• L is O, S, C1-4alkyl, C(O)NH, NHC(O), CH2C(O), C(O)CH2, CH2CH2C(O), CH2C(O)CH2, CH2C(O)NH, NH(CO)CH2;
• R1 is selected from the group consisting of H, Cl, F, Br, I, CN, NO2, NH2, CF3, CO2H, CO2NH2, CO2NHR5, CO2R5, C(O)R5, C(O)NH2, C(O)NHR5, or C1-C6 alkyl optionally substituted with alkoxy, alkenyl, alkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone, nitro, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol;
• R2 is H, OH, CN, NO2, NH2, unsubstituted C1-C6 alkyl, cycloalkyl, aryl, or heteroaryl;
• or C1-C6 alkyl, cycloalkyl, aryl, or heteroaryl substituted with alkoxy, alkenyl, alkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone, nitro, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol;
• or R1 and R2 together form a fused cycloalkyl, cycloheteroalkyl, aryl or heteraryl group;
• each R3 is selected, independently, from the group consisting of SO2NH2, SO2NHR5, NHSO2R5, NHCO2R5, NHC(O)R5, NHCONHR5, F, Cl, Br, I, NO2, C1-C6 alkyl, C1-C6 alkoxy, cycloheteroaryl, and fused cycloheteroalkyl, optionally substituted with sulfonyl;
• each R5 is selected, independently, from C1-C6 alkyl, C1-C6 cycloalkyl, aryl, heteroaryl, heterocycloalkyl, or heteroalkyl, any of which are optionally substituted with C1-C6 alkyl, C1-C6 alkoxyl, alkenyl, alkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone, nitro, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol;
• R6 is H, C1-C6 alkyl, CO2R5, CO2H, CO2NHR5;
• R7 is H, C1-C6 alkyl, C1-C6 alkoxyl, halide, hydroxyl, cyano, nitro, or amino;
• R8 is OH or ═O;
• n is 1-5;
• and
• p is 1 or 2
• or a pharmaceutically acceptable salt thereof.