Substituted pyrazolo[1,5-a][1,3,5]triazines as CDK inhibitors

A compound having Formula I:

• or a pharmaceutically acceptable salt or stereoisomer thereof,
• wherein:
• Z is
• R6 is a ring selected from Group B:
• R7 is H, NHR14, OR14, or a ring selected from Group B:
• each R14 is independently a ring selected from Group D:
• R8 is H, halogen, CN, C1-C6 alkyl, C1-C3 haloalkyl, or OR5, wherein the C1-C6 alkyl is optionally substituted with one substituent selected from the group consisting of NHR5 and OR5;
• R9 is H, halogen, CN, C1-C6 alkyl, C1-C3 haloalkyl, or OR5, wherein the C1-C6 alkyl is optionally substituted with one substituent selected from the group consisting of NHR5 and OR5;
• R10 is H, halogen, CN, C1-C6 alkyl, C1-C3 haloalkyl, or OR5, wherein the C1-C6 alkyl is optionally substituted with one substituent selected from the group consisting of NHR5 and OR5;
• each R12 is independently H or W;
• each R15 is independently H or W;
• each R16 is independently H, halogen, CN, C1-C6 alkyl, C1-C3 haloalkyl, NH2, OR5, or W;
• each R17 is independently H, C1-C6 alkyl, or C1-C3 haloalkyl;
• each R18 is independently H, halogen, CN, C1-C6 alkyl, C1-C3 haloalkyl, NH2, or OR5;
• each R19 is independently H, C1-C6 alkyl, C3-C10 cycloalkyl, or W;
• each o is independently 1, 2, or 3;
• each W is independently a structure selected from Group C:
• each L is independently absent, —NH—, or —O—;
• each R20 is independently H, halogen, CN, C1-C6 alkyl, C1-C3 haloalkyl, OR5, or heterocyclyl;
• each R21 is independently H, halogen, CN, C1-C6 alkyl, C1-C3 haloalkyl, OR5, or heterocyclyl;
• each R22 is independently H, halogen, CN, C1-C6 alkyl, NR5R5, NR19R20, NR19CH2C(O)NH2, OR5, C3-C10 cycloalkyl, or heterocyclyl;
• each n is independently 1, 2, or 3;
• R1 is H or CH3;
• X is N;
• Q is —C(O)—, —C(O)CH2—, —C(O)NH—, —NH—, —NHCH2—, —NHCH2CH2—, —NHC(O)—, —NHS(O)2—, —O—, or —OCH2—;
• Y is halogen, C1-C6 alkyl, C1-C3 haloalkyl, S(O)2R3, C3-C8 cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• wherein the C1-C6 alkyl is substituted with one or two substituents independently selected from the group consisting of NR5R5, OR5, heterocyclyl, aryl, and heteroaryl;
• wherein the C3-C8 cycloalkyl or heterocyclyl is optionally substituted with one or two substituents independently selected from the group consisting of C(O)R5, R3, and R4;
• and
• wherein the aryl or heteroaryl is optionally substituted with one or two substituents independently selected from the group consisting of halogen, C1-C6 alkyl, C(O)R5, NR5R5, OR5, heterocyclyl, heteroaryl, and R3;
• each R3 is independently H, halogen, CN, C1-C6 alkyl, C1-C3 haloalkyl, C(O)NH2, NR5R5, NHC(O)R5, OR5, S(O)2NR5R5, heterocyclyl, aryl, or heteroaryl, wherein each C1-C6 alkyl is optionally and independently substituted with one substituent selected from the group consisting of NH2, OR5, and S(O)2NR5R5;
• each R4 is independently H, halogen, CN, C1-C6 alkyl, C1-C3 haloalkyl, NR5R5, OR5, ═O, S(O)2NR5R5, heterocyclyl, aryl, or heteroaryl, wherein each C1-C6 alkyl is optionally and independently substituted with one substituent selected from the group consisting of NH2, OH, and S(O)2NR5R5;
• or
• any R3 and R4, together with the atoms to which they are attached, independently forms a heterocyclyl, aryl, or heteroaryl, wherein each heterocyclyl, aryl, and heteroaryl is optionally and independently fused or bridged;
• each R5 is independently H, C1-C6 alkyl, C1-C3 haloalkyl, C3-C6 cycloalkyl, heterocyclyl, or heteroaryl;
• wherein each heterocyclyl and heteroaryl is optionally and independently substituted with one or two substituents independently selected from the group consisting of halogen, C1-C6 alkyl, NR11R11, and OR11;
• and
• wherein each C1-C6 alkyl substituent of each heterocyclyl and heteroaryl is optionally and independently substituted with one substituent selected from the group consisting of NH2 and OH;
• each R11 is independently H, C1-C6 alkyl, C3-C10 cycloalkyl, or W;
• and
• R2 is C1-C6 alkyl, C1-C3 haloalkyl, or C(O)CH3;
• with the provisos that:
• (1) at least one of Z, R6, R7, R11, R12, R13, R15, R16, and R19 is W or a structure containing W;
• (2) if Y is a heterocyclyl containing a single sulfur atom, then the group containing the single sulfur atom is —S(O)2—;
• (3) if R11 is W, then R12 is H;
• (4) if R16 is W, then R12 is H;
• and
• (5) if R19 is W, then R15 is H.