Inhibitors of raf kinases

A compound, or pharmaceutically acceptable salt or solvate thereof, having the structure of Formula (I):

• wherein,
• R is selected from the group consisting of optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C4-C8 cycloalkylalkyl, optionally substituted C3-C6 heterocyclyl, optionally substituted C4-C8 heterocyclylalkyl, optionally substituted C6 aryl, optionally substituted 5- or 6-membered heteroaryl, and —CON(R1)2;
• R1 is selected from H or optionally substituted C1-C8 alkyl, wherein, optionally, two R1 substituents join to form a ring;
• X is H or F;
• Z is selected from:
• (a) —NRaRb, wherein Ra is selected from H, optionally substituted alkyl, optionally substituted C3-C6 alkenyl, optionally substituted C3-C6 alkynyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C3-C6 cycloalkylalkyl, optionally substituted heterocyclyl, or optionally substituted heterocyclylalkyl;
• and Rb is selected from optionally substituted alkyl, optionally substituted C3-C6 alkenyl, optionally substituted C3-C6 alkynyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C3-C6 cycloalkylalkyl, optionally substituted C4-C6 heterocyclyl, or optionally substituted heterocyclylalkyl;
• wherein m is 0, 1, 2, or 3;
• p is 0, 1, 2, 3, or 4;
• and
• each R11 is independently selected from amino, alkylamino, dialkylamino, —OH, halogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C1-C6 alkoxy, optionally substituted C2-C6 alkynyl, optionally substituted —S-alkyl, optionally substituted —SO2alkyl, optionally substituted C3-C6 cycloalkylalkyl, optionally substituted heterocyclyl, or optionally substituted heterocyclylalkyl;
• or two R11 groups together form an oxo;
• wherein m is 0, 1, 2, or 3;
• n is 0, 1, 2, or 3;
• p is 0, 1, 2, 3, or 4;
• W is O, S, S(O), SO2, NH or N (optionally substituted C1-C6 alkyl);
• and
• each R11 is independently selected from amino, alkylamino, dialkylamino, —OH, halogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C1-C6 alkoxy, optionally substituted C2-C6 alkynyl, optionally substituted —SO2alkyl, optionally substituted C3-C6 cycloalkylalkyl, optionally substituted heterocyclyl, or optionally substituted heterocyclylalkyl, or two R11 groups together form an oxo;
• wherein m is 0, 1, or 2;
• n is 0, 1, or 2;
• m1 is 0, 1, or 2;
• n1 is 0, 1, or 2 provided both m1 and n1 are not both 0;
• p is 0, 1, or 2;
• and q is 0, 1 or 2;
• W is O, S, S(O), SO2, NH or N (optionally substituted C1-C6 alkyl), CH2, CHR11, or C(R11)2;
• and
• each R11 is independently selected from amino, alkylamino, dialkylamino, —OH, halogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C1-C6 alkoxy, optionally substituted C2-C6 alkynyl, optionally substituted —SO2alkyl, optionally substituted C3-C6 cycloalkylalkyl, optionally substituted heterocyclyl, or optionally substituted heterocyclylalkyl, or two R11 groups together form an oxo;
• wherein m is 0, 1, or 2;
• n is 0, 1, or 2;
• m1 is 1, or 2;
• p is 0, 1, 2, or 3;
• W is O, S, S(O), SO2, NH or N (optionally substituted C1-C6 alkyl), CH2, CHR11, —CH2—CH2—, —CH2—CHR11—, —CH2—C(R11)2—, —CHR11—CH2—, —C(R11)2—CH2—, —NH—CH2—, —NH—CHR11—, —NH—C(R11)2—, —CH2—NH—, —CHR11—NH—, —C(R11)2—NH—, —N(R11)—CH2—, —N(R11)—CHR11—, —N(R11)—C(R11)2—, —CH2—N(R11)—, —CHR11—N(R11)—, —C(R11)2—N(R11)—, —O—CH2—, or —CH2—O—;
• each R11 is independently selected from amino, alkylamino, dialkylamino, —OH, halogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C1-C6 alkoxy, optionally substituted C2-C6 alkynyl, optionally substituted —SO2alkyl, optionally substituted C3-C6 cycloalkylalkyl, optionally substituted heterocyclyl, or optionally substituted heterocyclylalkyl, or two R11 groups together form an oxo;
• and R12 and R13 are each independently selected from H, or optionally substituted C1-C6 alkyl;
• wherein m is 0, 1, or 2;
• n is 0, 1, or 2;
• m1 is 0, 1, or 2;
• p is 0, 1, or 2;
• W is O, S, S(O), SO2, NH or N (optionally substituted C1-C6 alkyl), CH2, CHR11, or C(R11)2;
• each R11 is independently selected from amino, alkylamino, dialkylamino, —OH, halogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C1-C6 alkoxy, optionally substituted C2-C6 alkynyl, optionally substituted —SO2alkyl, optionally substituted C3-C6 cycloalkylalkyl, optionally substituted heterocyclyl, or optionally substituted heterocyclylalkyl, or two R11 groups together form an oxo;
• and R12 and R13 are each independently selected from H, or optionally substituted C1-C6 alkyl;
• wherein m is 0, 1, 2, or 3;
• n is 0, 1, 2, or 3;
• p is 0, 1, 2, 3, or 4;
• and each R11 is independently selected from amino, alkylamino, dialkylamino, —OH, halogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C1-C6 alkoxy, optionally substituted C2-C6 alkynyl, optionally substituted —S-alkyl, optionally substituted —SO2alkyl, optionally substituted C3-C6 cycloalkylalkyl, optionally substituted heterocyclyl, or optionally substituted heterocyclylalkyl;
• or two R11 groups together form an oxo;
• wherein m is 1, 2, or 3;
• n is 1, 2, or 3;
• p is 0, 1, or 2;
• and
• each R13 or R14 is independently selected from hydrogen, halogen, —CN, optionally substituted C1-C6 alkyl, or optionally substituted C3-C6 cycloalkyl;
• each R11 is independently selected from —OH, halogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C1-C6 alkoxy, optionally substituted C2-C6 alkynyl, optionally substituted —SO2alkyl, optionally substituted C3-C6 cycloalkylalkyl, optionally substituted heterocyclyl, or optionally substituted heterocyclylalkyl;
• or
• wherein m is 0, 1, or 2;
• n is 0, 1, or 2;
• m1 is 0, 1, or 2;
• p is 0, 1, or 2;
• and q is 0, 1 or 2;
• W is O, S, S(O), SO2, NH or N (optionally substituted C1-C6 alkyl), CH2, CHR11, or C(R11)2;
• and each R11 is independently selected from amino, alkylamino, dialkylamino, —OH, halogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C1-C6 alkoxy, optionally substituted C2-C6 alkynyl, optionally substituted —SO2alkyl, optionally substituted C3-C6 cycloalkylalkyl, optionally substituted heterocyclyl, or optionally substituted heterocyclylalkyl, or two geminal R11 groups together form an oxo.