Covalent cdk2-binding compounds for therapeutic purposes

A pharmaceutically acceptable compound of Formula:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• R1 is selected from the group consisting of:
• a)
• or
• b) a bicyclic heteroaryl which is optionally substituted with 1, 2, or 3 substituents selected from R7;
• R2 is independently selected at each instance from the group consisting of bond, alkyl, cycloalkyl, aryl, heterocycle, —S—, —O—, —NR6—, —(CH2)p—C(O)—NR6—, —(CH2CH2O)p—, —(OCH2CH2)p—, —NR6C(O)NR6—, —C(O)NR6—, —OC(O)NR6—, aryl-C(O)—NR6—, heteroaryl-C(O)—NR6—, bicycle, and heteroaryl, each of which is optionally substituted with 1, 2, or 3 substituents selected from R7;
• R3 is independently selected at each instance from bond, alkyl, cycloalkyl, aryl, heterocycle, —S—, —O—, —NR6—, —(CH2)p—C(O)—, —(CH2)p—C(O)—NR6—, —(CH2CH2O)p—, —(OCH2CH2)p—, —C(O)—, —NR6C(O)—, —NR6C(O)NR6—, —C(O)NR6—, —OC(O)NR6—, —NR6S(O)2NR6—, —S(O)2NR6—, aryl-C(O)—NR6—, heteroaryl-C(O)—NR6—, bicycle, and heteroaryl, each of which is optionally substituted with 1, 2, or 3 substituents selected from R7;
• p is independently selected from 1, 2, 3, 4, 5, and 6;
• R4 is a heteroaryl group with 1, 2, 3, or 4 nitrogen atoms, where the bond to the sulfur atom is through one of the nitrogen atoms present in the cycle, and each heteroaryl is optionally substituted with 1, 2, or 3 substituents selected from R7;
• R5 is selected from the group consisting of alkyl, cycloalkyl, naphthyl, heterocycle, —S—, —O—, —NR6—, —(CH2)p—C(O)—NR6—, —(CH2CH2O)p—, —(OCH2CH2)p—, —NR6C(O)NR6—, —C(O)NR6—, —OC(O)NR6—, heteroaryl-C(O)—NR6—, bicycle, and heteroaryl, each of which is optionally substituted with 1, 2, or 3 substituents selected from R7;
• R6 is independently selected at each instance hydrogen or alkyl;
• R7, R7a, R7b, R7c, and R7d are independently selected at each instance from the group consisting of hydrogen, halogen, alkyl, haloalkyl, alkenyl, cycloalkyl, heterocycle, aryl, heteroaryl, cyano, nitro, —C(O)R6, —OC(O)R6, —NR6C(O)R6, —C(O)OR6, —OC(O)OR6, —NR6C(O)OR6, —C(O)N(R6)2, —OC(O)N(R6)2, —NR6C(O)N(R6)2, —OR6, —N(R6)2, —S(O)R6, —S(O)2R6, —S(O)OR6, —S(O)2OR6, —S(O)N(R6)2, S(O)2N(R6)2, and —SR6, wherein each alkyl, haloalkyl, alkenyl, cycloalkyl, heterocycle, aryl, and heteroaryl is optionally substituted with 1, 2, or 3 substituents selected from R17;
• R17 is independently selected in each instance from the group consisting of hydrogen, halogen, alkyl, haloalkyl, alkenyl, cycloalkyl, heterocycle, aryl, heteroaryl, cyano, nitro, —C(O)R6, —OC(O)R6, —NR6C(O)R6, —C(O)OR6, —OC(O)OR6, —NR6C(O)OR6, —C(O)N(R6)2, —OC(O)N(R6)2, —NR6C(O)N(R6)2, —OR6, —N(R6)2, —S(O)R6, —S(O)2R6, —S(O)OR6, —S(O)2OR6, —S(O)N(R6)2, —S(O)2N(R6)2, and —SR6;
• R8a, R8b, R8c, and R8d are independently selected at each instance from the group consisting of R7 and R12 wherein at least one of R8a, R8b, R8c, and R8d is R12;
• R9 is alkyl, alkenyl, haloalkyl, cycloalkyl, heterocycle, —NR6C(O)—, —NR6C(O)NR6—, —C(O)NR6—, —OC(O)NR6—, —NR6S(O)2NR6—, —S(O)2NR6—, bicycle, or heteroaryl, each of which is optionally substituted with 1, 2, or 3 substituents selected from R7;
• R11 is hydrogen, halogen, alkyl, haloalkyl, alkenyl, cycloalkyl, heterocycle, naphthyl, heteroaryl, cyano, nitro, —C(O)R6, —OC(O)R6, —NR6C(O)R6, —C(O)OR6, —OC(O)OR6, —NR6C(O)OR6, —C(O)N(R6)2, —OC(O)N(R6)2, —NR6C(O)N(R6)2, —OR6, —N(R6)2, or —SR6, wherein each alkyl, haloalkyl, alkenyl, cycloalkyl, heterocycle, aryl, and heteroaryl optionally substituted with 1, 2, or 3 substituents selected from R17;
• R12 is halogen, alkyl, haloalkyl, alkenyl, cycloalkyl, heterocycle, aryl, heteroaryl, cyano, nitro, —C(O)R6, —OC(O)R6, —NR6C(O)R6, —C(O)OR6, —OC(O)OR6, —NR6C(O)OR6, —C(O)N(R6)2, —OC(O)N(R6)2, —NR6C(O)N(R6)2, —OR6, —N(R6)2, —S(O)R6, —S(O)2R6, —S(O)OR6, —S(O)2OR6, —S(O)N(R6)2, S(O)2N(R6)2, or —SR6, wherein each alkyl, haloalkyl, alkenyl, cycloalkyl, heterocycle, aryl, and heteroaryl is optionally substituted with 1, 2, or 3 substituents selected from R17;
• R13 is alkyl, haloalkyl, cycloalkyl, heterocycle, heteroaryl, aryl, —OR6, —N(R6)2, —C(O)R6, —NR6C(O)R6, —C(O)N(R6)2, or —NR6C(O)N(R6)2, each of which is optionally substituted with 1, 2, or 3 substituents selected from R7;
• R15 is alkyl, alkenyl, haloalkyl, cycloalkyl, aryl, heterocycle, —S—, —O—, —NR6—, —S-alkyl-, —O-alkyl-, —NR6-alkyl-, -alkyl-C(O)—, -alkyl-C(O)-alkyl-, -alkyl-C(O)—NR6-alkyl-, —C(O)—NR6-alkyl-, -alkyl-C(O)—NR6—, -alkyl-C(O)—O-alkyl-, —C(O)—O-alkyl-, -alkyl-C(O)—O—, —C(O)—, —NR6C(O)NR6—, —C(O)NR6—, —OC(O)NR6—, —NR6S(O)2NR6—, —S(O)2NR6—, bicycle, or heteroaryl, each of which except bond is optionally substituted with 1, 2, or 3 substituents independently selected from R7;
• R16 is a heteroaryl group, where the bond to the sulfur atom is through one of the nitrogen atoms present in the cycle, and R16 is optionally substituted with 1, 2, or 3 substituents selected from R7;
• and
• CDK2 Recognition Moiety is a molecule which can bind to or otherwise anchors to CDK2.