| abstract |
Compounds of formula (I), where: X1 is N or -CR6; R1 is -CN, or a group -Z-R12 where Z is -NR11 -, -NR11SO2-, among others; R2 is halo or a group -Y-R13, wherein Y is -alk C0-4-, -N (alk C0-1) -alk C0-4-, among others; R3 is H, C1-4 alk, or C1-4 haloalk; R4 is H, halo, R4a or R4b; R5 is H, halo, C1-8 alk, or C1-4 haloalk; R6 is H, halo, C1-8 alk, C1-4 haloalk, among others; R7 is H, halo, C1-8 alk, or C1-4 haloalk; R8 is H, halo, C1-8 alk, C1-4 haloalk, among others; R9 is H, halo, C1-8 alk, or C1-4 haloalk; Rx is a), b), c) or d); each of R10a, R10b, R10c, R10d, R10e, R10f, R10g, R10h, R10i, and R10j is H, halo, R10k, or R10l; R11 is H, R11a, or R11b; R12 is H, R12a, or R12b; R13 is R13a or R13b; R4a, R10k, R11a, R12a, and R13a is a monocyclic ring of 3, 4, 5, 6 or 7 membered saturated, partially saturated or unsaturated, among others; R4b, R8b, R10l, R11b, R12b, and R13b are C1-6 alk substituted by 0, 1, 2, 3, 4, or 5 group (s) selected from F, Cl, Br, -ORa, - Ohaloalc C1-4, or CN; Ra is H or Rb; and Rb is C1-6 alk, phenyl or benzyl, wherein the C1-6 alk is being substituted by 0, 1, 2 or 3 substituents selected from halo, -OH, -alc OC1-4, -NH2, -NHalc C1-4, -OC (= O) C1-4 alk, or -N (C1-4 alk) C1-4 alk; and the phenyl or benzyl is being substituted by 0, 1, 2 or 3 substituents selected from halo, C1-4 alk, C1-3 haloalk, -OH, -Oalc C1-4, -NH2, among others. Said compounds modulate the KIF18A protein, thereby altering the cell cycle process and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods for treating pathologies related to KIF18A activity. |