Cdk inhibitors and methods of use thereof

A compound of formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• Q is L1;
• CyA is a 5-6 membered heteroarylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• wherein CyA is substituted with m instances of RA in addition to Q and CyB;
• CyB is a saturated or partially unsaturated 3-14 membered carbocyclic ring;
• a saturated or partially unsaturated 3-14 membered heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• phenylene;
• or a 5-14 membered heteroarylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• wherein CyB is substituted with n instances of RB in addition to CyA and P;
• P is hydrogen or —L2-RP;
• RP is R;
• CyC is a saturated or partially unsaturated 3-14 membered carbocyclic ring;
• a saturated or partially unsaturated 3-14 membered heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• phenyl;
• or a 5-14 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• wherein CyC is substituted with p instances of RC in addition to Q;
• each instance of RA, RB, and RC is independently R1 or R2, wherein RA is substituted by qA instances of R3, RB is substituted by qB instances of R3, and RC is substituted by qC instances of R3;
• or
• two instances of RA, two instances of RB, two instances of RC, an instance of RA and an instance of RL, or an instance of RC and an instance of RL are taken together with their intervening atoms to form a 4-8 membered saturated, partially unsaturated or aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• wherein said ring is substituted with r instances of R3;
• each of L1 and L2 is independently a covalent bond, or a C1-5 saturated or unsaturated, straight or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by —CH(RL)—, —C(RL)2—, C34 cycloalkylene, 3-6 membered heterocycloalkylene, 5-6 membered heteroarylene, —NH—, —N(RL)—, —NHC(O)—, —N(RL)C(O)—, —C(O)NH—, —C(O)N(RL)—, —NHS(O)2—, —N(RL)S(O)2—, —S(O)2NH—, —S(O)2N(RL)—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —S(O)—, or —S(O)2—;
• wherein each of said C34 cycloalkylene, 3-6 membered heterocycloalkylene, and 5-6 membered heteroarylene is optionally substituted with one instance of R1 or C1-6 aliphatic;
• each instance of RL is independently R1 or R2, and is substituted by t instances of R3;
• each instance of R1 is independently oxo, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —S(O)NR2, —C(O)R, —C(O)OR, —C(O)NR2, —C(NR)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(NR)R, —N(R)C(O)NR2, —N(R)C(NR)NR2, —N(R)S(O)2NR2, —N(R)S(O)R, —N(R)S(O)2R;
• each instance of R2 is independently C1-7 aliphatic;
• phenyl;
• a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 3-7 membered saturated or partially unsaturated carbocyclic ring;
• a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each instance of R3 is independently oxo, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —S(O)NR2, —S(O)2F, —OS(O)2F, —C(O)R, —C(O)OR, —C(O)NR2, —C(NR)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(NR)R, —N(R)C(O)NR2, —N(R)C(NR)NR2, —N(R)S(O)2NR2, —N(R)S(O)R, —N(R)S(O)2R, or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each R is independently hydrogen, or an optionally substituted group selected from C1-6 aliphatic, a saturated or partially unsaturated 3-7 membered carbocyclic ring, phenyl, a 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:
• two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur;
• and
• each of m, n, p, qA, qB, qC, r, and t is independently 0, 1, 2, 3, or 4.

A compound of formula II, III, IV, V, VI, or VII:

• or a pharmaceutically acceptable salt thereof, wherein:
• Q is L1;
• CyA is a 5-6 membered heteroarylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• wherein CyA is substituted with m instances of RA in addition to Q and CyB;
• CyB is a saturated or partially unsaturated 3-14 membered carbocyclic ring;
• a saturated or partially unsaturated 3-14 membered heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• phenylene;
• or a 5-14 membered heteroarylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• wherein CyB is substituted with n instances of RB in addition to CyA and P or X;
• X is selected from O, NRX, and S;
• Y is selected from O, NRY, and S;
• each instance of RX and RY is independently R;
• P is hydrogen or —L2-RP;
• RP is R;
• CyC is a saturated or partially unsaturated 3-14 membered carbocyclic ring;
• a saturated or partially unsaturated 3-14 membered heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• phenyl;
• or a 5-14 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• wherein CyC is substituted with p instances of RC in addition to Q;
• each instance of RA, RB, and Rc is independently R1 or R2, wherein RA is substituted by qA instances of R3, RB is substituted by qB instances of R3, and RC is substituted by qC instances of R3;
• or
• two instances of RA, two instances of RB, two instances of RC, an instance of RA and an instance of RL, or an instance of RC and an instance of RL are taken together with their intervening atoms to form a 4-8 membered saturated, partially unsaturated or aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• wherein said ring is substituted with r instances of R3;
• each of L and L2 is independently a covalent bond, or a C1-5 saturated or unsaturated, straight or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by —CH(RL)—, —C(RL)2—, C34 cycloalkylene, 3-6 membered heterocycloalkylene, 5-6 membered heteroarylene, —NH—, —N(RL)—, —NHC(O)—, —N(RL)C(O)—, —C(O)NH—, —C(O)N(RL)—, —NHS(O)2—, —N(RL)S(O)2—, —S(O)2NH—, —S(O)2N(RL)—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —S(O)—, or —S(O)2—;
• wherein each of said C34 cycloalkylene, 3-6 membered heterocycloalkylene, and 5-6 membered heteroarylene is optionally substituted with one instance of R1 or C1-6 aliphatic;
• each instance of RL is independently R1 or R2, and is substituted by t instances of R3;
• each instance of R1 is independently oxo, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —S(O)NR2, —C(O)R, —C(O)OR, —C(O)NR2, —C(NR)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(NR)R, —N(R)C(O)NR2, —N(R)C(NR)NR2, —N(R)S(O)2NR2, —N(R)S(O)R, or —N(R)S(O)2R;
• each instance of R2 is independently C1-7 aliphatic;
• phenyl;
• a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 3-7 membered saturated or partially unsaturated carbocyclic ring;
• a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each instance of R3 is independently oxo, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —S(O)NR2, —S(O)2F, —OS(O)2F, —C(O)R, —C(O)OR, —C(O)NR2, —C(NR)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(NR)R, —N(R)C(O)NR2, —N(R)C(NR)NR2, —N(R)S(O)2NR2, —N(R)S(O)R, —N(R)S(O)2R, or an optionally substituted group selected from C1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each R is independently hydrogen, or an optionally substituted group selected from C1-6 aliphatic, a saturated or partially unsaturated 3-7 membered carbocyclic ring, phenyl, a 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:
• two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur;
• and
• each of m, n, p, qA, qB, qC, r, and t is independently 0, 1, 2, 3, or 4.