CPC C07D 487/04 (2013.01) [A61P 35/00 (2018.01); C12Q 1/6886 (2013.01); C12Q 2600/156 (2013.01)] | 30 Claims |
1. A method of treating cancer in a patient comprising administering to the patient a therapeutically effective amount of a compound having Formula I:
or a pharmaceutically acceptable salt or solvate thereof, wherein:
each of R1 and R2 is independently selected from hydrogen, halo, cyano, optionally substituted alkyl, optionally substituted alkenyl, and optionally substituted alkynyl;
R3 is an optionally substituted phenyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, optionally substituted pyrazinyl, optionally substituted pyridazinyl, or optionally substituted pyrazolyl;
each of X11 and X12 is independently selected from N and CH;
R5′ is selected from hydrogen, optionally substituted (C1-C6) alkyl, optionally substituted (C2-C6) alkenyl, optionally substituted (C2-C6) alkynyl, optionally substituted (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, cyano, halo, sulfonamido, —C(═O)R23, —C(═O)OR24, —NR32aR32b, —NR31aC(═O)R25, —NR31aC(═O)NR31aR31b, —C(═O)NR31aR31b, —S(O)2R27, —NR31aSO2R27, optionally substituted (C6-C14) aryl, optionally substituted (C6-C14) ar-(C1-C2) alkyl, optionally substituted heteroaryl, optionally substituted heteroar-(C1-C2) alkyl, optionally substituted (C3-C8) cycloalkyl, optionally substituted ((C3-C8) cycloalkyl)-(C1-C2) alkyl, optionally substituted heterocyclo, optionally substituted heterocyclo-(C1-C2) alkyl, optionally substituted —O—(C6-C14) aryl, optionally substituted —O—(C6-C14) ar-(C1-C2) alkyl, optionally substituted —O-heteroaryl, optionally substituted —O-heteroar-(C1-C2) alkyl, optionally substituted —O—(C3-C8) cycloalkyl, optionally substituted —O—((C3-C8) cycloalkyl)-(C1-C2) alkyl, optionally substituted —O-heterocyclo, optionally substituted —O-heterocyclo-(C1-C2) alkyl;
R5 is selected from optionally substituted (C1-C6) alkyl, optionally substituted (C2-C6) alkenyl, optionally substituted (C2-C6) alkynyl, optionally substituted (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, cyano, halo, sulfonamido, —C(═O)R23, —C(═O)OR24, —NR32aR32b, —NR31aC(═O)R25, —NR31aC(═O)NR31aR31a(═O)NR31aR31b, —S(O)2R27, —NR31aSO2R27, optionally substituted (C6-C14) aryl, optionally substituted (C6-C14) ar-(C1-C2) alkyl, optionally substituted heteroaryl, optionally substituted heteroar-(C1-C2) alkyl, optionally substituted (C3-C8) cycloalkyl, optionally substituted ((C3-C8) cycloalkyl)-(C1-C2) alkyl, optionally substituted heterocyclo, optionally substituted heterocyclo-(C1-C2) alkyl, optionally substituted —O—(C6-C14) aryl, optionally substituted —O—(C6-C14) ar-(C1-C2) alkyl, optionally substituted —O-heteroaryl, optionally substituted —O-heteroar-(C1-C2) alkyl, optionally substituted —O—(C3-C8) cycloalkyl, optionally substituted —O—((C3-C8) cycloalkyl)-(C1-C2) alkyl, optionally substituted —O-heterocyclo, optionally substituted —O-heterocyclo-(C1-C2) alkyl; or
one of R5 and one of R5′ on adjacent atoms are taken together with the atoms to which they are attached to form an optionally substituted (C6-C14) aryl ring; or one of R5 and one of R5′ on adjacent atoms are taken together with the atoms to which they are attached to form an optionally substituted heteroaryl ring; or one of R5 and one of R5′ on adjacent atoms are taken together with the atoms to which they are attached to form an optionally substituted (C3-C8) cycloalkyl ring; or one of R5 and one of R5′ on adjacent atoms are taken together with the atoms to which they are attached to form an optionally substituted heterocycloalkyl ring; or one of R5 and one of R5′ on adjacent atoms on the same atom to which they are attached are taken together to form an optionally substituted spirocycloalkyl ring; or one of R5 and one of R5′ on adjacent atoms on the same atom to which they are attached are taken together to form an optionally substituted spiroheterocycloalkyl ring;
each of R6 and R7 is independently selected from hydrogen, halo, cyano, optionally substituted alkyl, optionally substituted alkenyl, and optionally substituted alkynyl;
R23 is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, amino, alkylamino, dialkylamino, cycloalkylamino, hydroxyalkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, (cycloalkylamino)alkyl, (cycloalkyl)alkyl, aralkyl, (heterocyclo)alkyl, (heteroaryl)alkyl, (amino)(hydroxy)alkyl, (aralkylamino)alkyl, optionally substituted heterocyclo, optionally substituted heteroaryl, optionally substituted aryl, and optionally substituted cycloalkyl;
R31a and R31b are each independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, hydroxyalkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, alkoxyalkyl, cycloalkyl, (cycloalkyl)alkyl, (heterocyclo)alkyl, aralkyl, and (heteroaryl)alkyl; and
each of R24, R25, R27, R32a, and R32b is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, amino, alkylamino, dialkylamino, cycloalkylamino, hydroxyalkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, (cycloalkylamino)alkyl, (cycloalkyl)alkyl, aralkyl, (heterocyclo)alkyl, (heteroaryl)alkyl, (amino)(hydroxy)alkyl, (aralkylamino)alkyl, alkoxyalkyl, optionally substituted heterocyclo, optionally substituted heteroaryl, optionally substituted aryl, and optionally substituted cycloalkyl.
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