Pharmaceutical composition and use thereof

A method for the treatment of a cancer, which comprises administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a CDK inhibitor or a pharmaceutically acceptable salt thereof:

• is selected from the group consisting of
• B is a C4-7 carbocyclic ring;
• R1 is H, unsubstituted C1-4 alkyl, unsubstituted C3-8 cycloalkyl, unsubstituted 4 to 12-membered heterocycloalkyl, ORa, or NRaRb;
• the heteroatom of the heterocycloalkyl is independently selected from nitrogen, oxygen, and sulfur, the number of the heteroatom is 1-4;
• n is 0, 1, or 2;
• R2, R3, R4, R5, R7, R8, R9 and R10 are independently selected from the group consisting of H, F, Cl, CH3, and CF3;
• R6 is
• each of Ra is independently H or unsubstituted C1-4 alkyl;
• each of Rb is independently H or unsubstituted C1-4 alkyl;
• Rc and Rd are substituents on one carbon atom of ring B, wherein
• Rc is H, C1-3 alkyl, C1-3 alkylene-ORa, ORa, or halo;
• Rd is H, C1-3 alkyl, C1-3 alkylene-ORa, ORa, or halo;
• or
• Rc and Rd are taken together with the carbon to which they are attached to form a 4 to 6-membered spiro carbocyclic substituent, optionally containing an oxygen atom;
• and
• Re is —C(═O)ORa, —C(═O)NRaRb, or —C(═O)NHSO2CH3;
• and
• wherein the cancer is liposarcoma or lung cancer.

A kit comprising separate containers in a single package:

• in one container a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and in a second container a pharmaceutical composition comprising a CDK inhibitor or a pharmaceutically acceptable salt thereof:
• is selected from the group consisting of
• B is a C4-7 carbocyclic ring;
• R1 is H, unsubstituted C1-4 alkyl, unsubstituted C3-8 cycloalkyl, unsubstituted 4 to 12-membered heterocycloalkyl, ORa, or NRaRb;
• the heteroatom of the heterocycloalkyl is independently selected from nitrogen, oxygen, and sulfur, the number of the heteroatom is 1-4;
• n is 0, 1, or 2;
• R2, R3, R4, R5, R7, R8, R9 and R10 are independently selected from the group consisting of H, F, Cl, CH3, and CF3;
• R6 is
• each of Ra is independently H or unsubstituted C1-4 alkyl;
• each of Rb is independently H or unsubstituted C1-4 alkyl;
• Rc and Rd are substituents on one carbon atom of ring B, wherein
• Rc is H, C1-3 alkyl, C1-3 alkylene-ORa, ORa, or halo;
• Rd is H, C1-3 alkyl, C1-3 alkylene-ORa, ORa, or halo;
• or
• Rc and Rd are taken together with the carbon to which they are attached to form a 4 to 6-membered spiro carbocyclic substituent, optionally containing an oxygen atom;
• and
• Re is —C(═O)ORa, —C(═O)NRaRb, or —C(═O)NHSO2CH3.