Cdk inhibitors and methods of use thereof

A compound of formula I′:

• or a pharmaceutically acceptable salt thereof, wherein:
• Q is L1;
• Z is H, halogen, or CyB;
• L is a covalent bond or a bivalent C1-3 aliphatic group, wherein one carbon is optionally replaced by —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)—, —S(O)2—, C3-6 cycloalkylene, or 3-6 membered heterocycloalkylene having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• wherein each of said C3-6 cycloalkylene and 3-6 membered heterocycloalkylene is optionally substituted with one instance of R1 or C1-6 aliphatic;
• CyA is a phenyl;
• a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur;
• an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur;
• a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring;
• a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur;
• a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur;
• a 10-14 membered saturated or partially unsaturated tricyclic heterocyclic ring having 1-6 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur;
• or a 10-14 membered tricyclic heteroaryl ring having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• wherein CyA is substituted with m instances of RA;
• CyB is a phenyl;
• a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur;
• an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur;
• a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring;
• a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur;
• a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur;
• a 10-14 membered saturated or partially unsaturated tricyclic heterocyclic ring having 1-6 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur;
• or a 10-14 membered tricyclic heteroaryl ring having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• wherein CyB is substituted with n instances of RB;
• CyX is phenyl, naphthyl, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur;
• an 8-12 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur;
• a 7-12 membered saturated, partially unsaturated, or aromatic bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur;
• or a 10-15 membered saturated, partially unsaturated, or aromatic tricyclic heterocyclic ring having 1-6 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur;
• wherein CyX is substituted with u instances of L2-X0;
• X0 is hydrogen, a halogen, oxo, CN, or a group selected from C1-8 aliphatic, a saturated or partially unsaturated 3-14 membered monocyclic or bicyclic carbocyclic ring, phenyl, a 3-10 membered saturated or partially unsaturated monocyclic or bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-14 membered monocyclic or bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• wherein X0 is substituted with p instances of RX;
• Y is N or CH;
• each instance of RA, RB, and RX is independently R1 or R2, wherein RA is substituted by qA instances of R3, RB is substituted by qB instances of R3, and RX is substituted with qX instances of R3;
• or
• two instances of RA, two instances of RB, two instances of RX, two instances of X0, an instance of X0 and an instance of RA, or an instance of RA and an instance of RX are taken together with their intervening atoms to form a 3-8 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 C1-6 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—, C3-6 cycloalkylene, 3-6 membered heterocycloalkylene having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 5-6 membered heteroarylene having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, —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 C3-6 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, —SR(O)NR, —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 —P(O)R2;
• each instance of R2 is independently C1-7 aliphatic;
• —O—C1-7 aliphatic;
• C1-4 haloalkyl;
• 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 monocyclic 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, —SR(O)NR, —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, qX, r, t, and u is independently 0, 1, 2, 3, or 4.