Cyclin dependent kinase inhibitors

A method of the treatment of cancer in a subject in need thereof, comprising administering to the subject a therapeutically effect amount of a compound having formula (IX):

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is H, F, Cl, CN, C1-C2 alkyl or C1-C2 fluoroalkyl, where each said C1-C2 alkyl and C1-C2 fluoroalkyl is optionally substituted by R20;
• R2 is H, C1-C5 alkyl, C1-C5 fluoroalkyl, C3-C8 cycloalkyl or 3-6 membered heterocyclyl, where each said C1-C5 alkyl and C1-C5 fluoroalkyl is optionally substituted by R20 and each said C3-C8 cycloalkyl and 3-6 membered heterocyclyl is optionally substituted by R21;
• R4 is H, C1-C4 alkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy or C1-C4 fluoroalkoxy, where each said C1-C4 alkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy and C1-C4 fluoroalkoxy is optionally substituted by R20;
• R6 is H, F, Cl, CN, CH3, CH2F, CHF2 or CF3,
• R7 and R8 are independently H, F, Cl, CN, C1-C2 alkyl, C1-C2 fluoroalkyl, C1-C2 alkoxy or C1-C2 fluoroalkoxy, where each said C1-C2 alkyl, C1-C2 fluoroalkyl, C1-C2 alkoxy and C1-C2 fluoroalkoxy is optionally substituted by R20;
• R9 is H, OH, NH2, NHCH3 or N(CH3)2;
• each R10 is independently F, CN, C1-C2 alkyl or C1-C2 fluoroalkyl, where each said C1-C2 alkyl and C1-C2 fluoroalkyl is optionally substituted by R20;
• R11 is H, C1-C4 alkyl, C1-C4 fluoroalkyl, SO2R14, SO2NR15R16, COR17, COOR17 or CONR18R19;
• R14 is C1-C4 alkyl or C1-C4 fluoroalkyl;
• each R15 and R16 is independently H or CH3,
• R17 is C1-C4 alkyl or C1-C4 fluoroalkyl, where each said C1-C4 alkyl and C1-C4 fluoroalkyl is optionally substituted by R29;
• each R18 and R19 is independently H, C1-C4 alkyl or C1-C4 fluoroalkyl, where each said C1-C4 alkyl and C1-C4 fluoroalkyl is optionally substituted by R20;
• each R20 is independently OH, C1-C2 alkoxy, C1-C2 fluoroalkoxy, CN or NR22R23;
• each R21 is independently F, OH, CN, NR22R23, C1-C4 alkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy or C1-C4 fluoroalkoxy, where each said C1-C4 alkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy and C1-C4 fluoroalkoxy is optionally further substituted by OH, NH2, NHCH3 or N(CH3)2;
• each R22 and R23 is independently H, C1-C2 alkyl or C1-C2 fluoroalkyl;
• or
• R22 and R23 may be taken together with the nitrogen atom to which they are attached to form an azetidinyl ring, which is optionally substituted by F or OH;
• and n is 0, 1, 2, 3 or 4,
• wherein the cancer is selected from the group consisting of breast cancer, ovarian cancer, bladder cancer, uterine cancer, prostate cancer, lung cancer, esophageal cancer, head and neck cancer, colorectal cancer, kidney cancer, liver cancer, pancreatic cancer, stomach cancer and thyroid cancer.

A method of the treatment of cancer in a subject in need thereof, comprising administering to the subject a therapeutically effect amount of a compound having Formula (II):

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is H, F, Cl, CN, C1-C2 alkyl or C1-C2 fluoroalkyl, where each said C1-C2 alkyl and C1-C2 fluoroalkyl is optionally substituted by R20;
• U is NR2 or CR3;
• V is N or CR4 when U is NR2;
• and
• V is NR5 when U is CR3,
• X is CR6 or N;
• Y is CR7 or N;
• Z is CR8 or N;
• R2 and R3 are H, C1-C5 alkyl, C1-C5 fluoroalkyl, C3-C8 cycloalkyl or 3-6 membered heterocyclyl, where each said C1-C5 alkyl and C1-C5 fluoroalkyl is optionally substituted by R20 and each said C3-C8 cycloalkyl and 3-6 membered heterocyclyl is optionally substituted by R21;
• R4 is H, C1-C4 alkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy or C1-C4 fluoroalkoxy, where each said C1-C4 alkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy and C1-C4 fluoroalkoxy is optionally substituted by R20;
• R5 is H, C1-C4 alkyl or C1-C4 fluoroalkyl, where each said C1-C4 alkyl and C1-C4 fluoroalkyl is optionally substituted by R20;
• R6 is H, F, Cl, CN, CH3, CH2F, CHF2 or CF3,
• R7 and R8 are independently H, F, Cl, CN, C1-C2 alkyl, C1-C2 fluoroalkyl, C1-C2 alkoxy or C1-C2 fluoroalkoxy, where each said C1-C2 alkyl, C1-C2 fluoroalkyl, C1-C2 alkoxy and C1-C2 fluoroalkoxy is optionally substituted by R20;
• R9 is H, OH, NH2, NHCH3 or N(CH3)2;
• each R10 is independently F, CN, C1-C2 alkyl or C1-C2 fluoroalkyl, where each said C1-C2 alkyl and C1-C2 fluoroalkyl is optionally substituted by R20;
• Q is NR11 or O;
• or
• Q is CR12R13, where R12 and R13 are taken together with the C atom to which they are attached to form a 4-6 membered heterocyclic ring containing NR11 or O as a ring member, which ring is optionally further substituted by R10;
• R11 is H, C1-C4 alkyl, C1-C4 fluoroalkyl, SO2R14, SO2NR15R16, COR17, COOR17 or CONR18R19;
• R14 is C1-C4 alkyl or C1-C4 fluoroalkyl;
• each R15 and R16 is independently H or CH3;
• R17 is C1-C4 alkyl, C1-C4 fluoroalkyl, where each said C1-C4 alkyl and C1-C4 fluoroalkyl is optionally substituted by R20;
• each R18 and R19 is independently H, C1-C4 alkyl or C1-C4 fluoroalkyl, where each said C1-C4 alkyl and C1-C4 fluoroalkyl is optionally substituted by R20;
• each R29 is independently OH, C1-C2 alkoxy, C1-C2 fluoroalkoxy, CN or NR22R23;
• each R21 is independently F, OH, CN, NR22R23, C1-C4 alkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy or C1-C4 fluoroalkoxy, where each said C1-C4 alkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy and C1-C4 fluoroalkoxy is optionally further substituted by OH, NH2, NHCH3 or N(CH3)2;
• each R22 and R23 is independently H, C1-C2 alkyl or C1-C2 fluoroalkyl;
• or
• R22 and R23 may be taken together with the nitrogen atom to which they are attached to form an azetidinyl ring, which is optionally substituted by F or OH;
• n is 0, 1, 2, 3 or 4;
• p is 1, 2 or 3;
• and
• q is 0, 1, 2 or 3;
• wherein the sum of p and q is an integer from 1 to 4.