RAF kinase modulators and methods of use

A compound of Formula II:

• or a pharmaceutically acceptable salt thereof, wherein
• each of A3 and A4, independently, is CH;
• X is CR2R2, C(O), NR2, O or S(O)p wherein p is 0, 1, or 2;
• Z1 is
• Z2 is
• R1 is H;
• each R2 independently, is H, halo, haloalkyl, NO2, CN or C1-6-alkyl;
• R3 is NR5R5, NR5R6, OR5, SR5, OR6, SR6, C(O)R5, C(S)R5, C(NCN)R5, C(O)R6, C(S)R6, C(NCN)R6, OC(O)R5, COOR5, C(O)NR5R5, C(O)NR5R6, NR5C(O)R5, NR5C(O)R6, NR5C(O)NR5R5, NR5C(O)NR5R6, NR5(COOR5), NR5(COOR6), S(O)2R5, S(O)2R6, S(O)2NR5R5, S(O)2NR5R6, NR5S(O)2NR5R6, NR5S(O)2R5 or NR5S(O)2R6;
• each R4, independently, is H, halo, haloalkyl or C1-8-alkyl, wherein said C1-8-alkyl is optionally substituted independently with 1-5 substituents of R7;
• each R5 independently, is H, C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, C3-6-cycloalkyl or C4-8-cycloalkenyl, each of the C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C3-10-cycloalkyl and C4-10-cycloalkenyl optionally comprising 1-4 heteroatoms selected from N, O and S and optionally substituted with one or more substituents of R6 or R7, NR6R7, NR7R7, OR6, SR6, OR7, SR6, C(O)R7, OC(O)R6, COOR6, C(O)R7, OC(O)R7, COOR7, C(O)NR6R7, NR7C(O)R6, C(O)NR7R7, NR7C(O)R7, NR7C(O)NR6R7, NR7C(O)NR7R7, NR7(COOR6), NR7(COOR7), OC(O)NR6R7, OC(O)NR7R7, S(O)2R6, S(O)2R7, S(O)2NR6R7, S(O)2NR7R7, NR7S(O)2NR6R7, NR7S(O)2NR7R7, NR7S(O)2R6, NR7S(O)2R7, NR7S(O)2R6 or NR7S(O)2R7;
• R6 is a partially or fully saturated or unsaturated 5-8 membered monocyclic or 6-12 membered bicyclic ring system, said ring system formed of carbon atoms optionally including 1-3 heteroatoms if monocyclic or 1-6 heteroatoms if bicyclic, said heteroatoms selected from O, N, or S, and wherein each ring of said ring system is optionally substituted independently with 1-5 substituents of R7;
• alternatively, R5 and R6 taken together form a partially or fully saturated or unsaturated 5-6 membered ring of carbon atoms optionally including 1-3 heteroatoms selected from O, N, or S, and the ring optionally substituted independently with 1-5 substituents of R7;
• and
• each R7, independently, is H, F, Cl, Br, I, haloalkyl, CN, OH, NO2, NH2, C1-8-alkyl, —O—C1-8-alkyl, —C1-6-alkyl-O—C1-6-alkyl, —S—C1-8-alkyl, —C1-6-alkyl-S—C1-6-alkyl, —NH—C1-8-alkyl, —N-di-C1-8-alkyl, —C1-6-alkyl-NH—C1-6-alkyl, C2-8-alkenyl, C2-8-alkynyl, C3-6-cycloalkyl, oxo, acetyl, benzyl or a partially or fully saturated or unsaturated 5-8 membered monocyclic or 6-12 membered bicyclic ring system, said ring system formed of carbon atoms optionally including 1-3 heteroatoms if monocyclic or 1-6 heteroatoms if bicyclic, said heteroatoms selected from O, N, or S, wherein each of said C1-8-alkyl, C1-8-alkenyl, C1-8-alkynyl and ring of said ring system is optionally substituted independently with 1-5 substituents of halo, haloalkyl, CN, NO2, NH2, OH, methyl, methoxyl, ethyl, ethoxyl, propyl, propoxyl, isopropyl, cyclopropyl, butyl, isobutyl, tert-butyl, methylamino, dimethylamino, ethylamino, diethylamino, isopropylamino, benzyl or phenyl.