Kif18a inhibitors

A compound of formula I:

• or any pharmaceutically-acceptable salt thereof, wherein:
• X1 is N or —CR6;
• R1 is —CN, or a group —Z—R12 wherein Z is —C0-4alk-, —NR11—, —NR11SO2—, —SO2NR11—, —NR11—S(═O)(═NH), —S(═O)(═NH)—, —S—, —S(═O)—, —SO2—, C0-4alk-O—, —(C═O)—, —(C═O)NR11—, —C═N(OH)—, or —NR11(C═O);
• or
• the group —Z—R12 is —N═S(═O)—(R12)2, wherein the two R12 pair can alternatively combine with the sulfur atom attached to each of them to form a saturated or partially-saturated 3-, 4-, 5-, or 6-membered monocyclic ring containing 0, 1, 2 or 3 N atoms and 0, 1, or 2 atoms selected from O and S;
• R2 is halo or a group —Y—R13, wherein Y is —C0-4alk-, —N(C0-1alk)-C0-4alk-, —C(═O)NRaRa(C1-4alk), —O—C0-4alk-, S, S═O, S(═O)2, —SO2NR13, or —S(═O)(═NH)—;
• R3 is H, C1-4alk, or C1-4haloalk;
• R4 is H, halo, R4a or R4b;
• R5 is H, halo, C1-8alk, or C1-4haloalk;
• R6 is H, halo, C1-8alk, C1-4haloalk, —O—C1-8alk, or —O—R6a;
• wherein R6a is a saturated or partially-saturated 3-, 4-, 5-, or 6-membered monocyclic ring containing 0, 1, 2 or 3 N atoms and 0, 1, or 2 atoms selected from O and S;
• R7 is H, halo, C1-8alk, or C1-4haloalk;
• R8 is H, halo, C1-8alk, C1-4haloalk, —OH, —O—R8a, or —O—R8b;
• R9 is H, halo, C1-8alk, or C1-4haloalk;
• Rx is selected from the group consisting of
• Each of R10a, R10b, R10c, R10d, R10e, R10f, R10g, R10h, R10i, and R10j is H, halo, R10k, or R10l;
• or alternatively, each of R10a and R10b pair, R10c and R10d pair, R10e and R10f pair, R10g and R10h pair, or R10i and R10j pair, independently, can combine with the carbon atom attached to each of them to form a saturated or partially-saturated 3-, 4-, 5-, 6-membered monocyclic ring spiro to the Rx ring;
• wherein said 3-, 4-, 5-, 6-membered monocyclic ring contains 0, 1, 2 or 3 N atoms and 0, 1, or 2 atoms selected from O and S, and further wherein said 3-, 4-, 5-, 6-membered monocyclic ring is substituted by 0, 1, 2 or 3 group(s) selected from F, Cl, Br, C1-6alk, C1-4haloalk, —ORa, —OC1-4haloalk, CN, —NRaRa, or oxo;
• R11 is H, R11a, or R11b;
• R12 is H, R12a, or R12b;
• R13 is R13a or R13b;
• R4a, R8a, R10k, R11a, R12a, and R13a is independently, at each instance, selected from the group consisting of a saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered monocyclic or 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered bicyclic ring containing 0, 1, 2 or 3 N atoms and 0, 1, or 2 atoms selected from O and S, which is substituted by 0, 1, 2 or 3 group(s) selected from F, Cl, Br, C1-6alk, C1-4haloalk, —ORa, —OC1-4haloalk, CN, —C(═O)Rb, —C(═O)ORa, —C(═O)NRaRa, —C(═NRa)NRaRa, —OC(═O)Rb, —OC(═O)NRaRa, —OC2-6alkNRaRa, —OC2-6alkORa, —SRa, —S(═O)Rb, —S(═O)2Rb, —S(═O)2NRaRa, —NRaRa, —N(Ra)C(═O)Rb, —N(Ra)C(═O)ORb, —N(Ra)C(═O)NRaRa, —N(Ra)C(═NRa)NRaRa, —N(Ra)S(═O)2Rb, —N(Ra)S(═O)2NRaRa, —NRaC2-6alkNRaRa, —NRaC2-6alkORa, —C1-6alkNRaRa, —C1-6alkORa, —C1-6alkN(Ra)C(═O)Rb, —C1-6alkOC(═O)Rb, —C1-6alkC(═O)NRaRa, —C1-6alkC(═O)ORa, R14, and oxo;
• R4b, R8b, R10l, R11b, R12b, and R13b is independently, at each instance, selected from the group consisting of C1-6alk substituted by 0, 1, 2, 3, 4, or 5 group(s) selected from F, Cl, Br, —ORa, —OC1-4haloalk, or CN;
• R14 is independently, at each instance, selected from the group consisting of a saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered monocyclic or 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered bicyclic ring containing 0, 1, 2 or 3 N atoms and 0 or 1 atoms selected from O and S, which is substituted by 0, 1, 2 or 3 group(s) selected from F, Cl, Br, C1-6alk, C1-4haloalk, —ORa, —OC1-4haloalk, CN, —C(═O)Rb, —C(═O)ORa, —C(═O)NRaRa, —C(═NRa)NRaRa, —OC(═O)Rb, —OC(═O)NRaRa, —OC2-6alkNRaRa, —OC2-6alkORa, —SRa, —S(═O)Rb, —S(═O)2Rb, —S(═O)2NRaRa, —NRaRa, —N(Ra)C(═O)Rb, —N(Ra)C(═O)ORb, —N(Ra)C(═O)NRaRa, —N(Ra)C(═NRa)NRaRa, —N(Ra)S(═O)2Rb, —N(Ra)S(═O)2NRaRa, —NRaC2-6alkNRaRa, —NRaC2-6alkORa, —C1-6alkNRaRa, —C1-6alkORa, —C1-6alkN(Ra)C(═O)Rb, —C1-6alkOC(═O)Rb, —C1-6alkC(═O)NRaRa, —C1-6alkC(═O)ORa, and oxo;
• Ra is independently, at each instance, H or Rb;
• and
• Rb is independently, at each instance, C1-6alk, phenyl, or benzyl, wherein the C1-6alk is being substituted by 0, 1, 2 or 3 substituents selected from halo, —OH, —OC1-4alk, —NH2, —NHC1-4alk, —OC(═O)C1-4alk, or —N(C1-4alk)C1-4alk;
• and the phenyl or benzyl is being substituted by 0, 1, 2 or 3 substituents selected from halo, C1-4alk, C1-3haloalk, —OH, —OC1-4alk, —NH2, —NHC1-4alk, —OC(═O)C1-4alk, or —N(C1-4alk)C1-4alk.