SELECTIVE CANCER THERAPEUTIC AGENTS: CDK4 / 6 INHIBITORS

Abstract

This description describes selective and potent CDK 4 / 6 inhibitors that exhibit advantageous inhibition of cancer growth, even at low concentrations. This class of anticancer CDK 4 / 6 inhibitors consists of substituted pyrrolopyrimidine compounds of formula 1A, which contain a fatty acid moiety. These compounds can be used as pharmaceuticals for anticancer therapies and are useful for the treatment, prevention, and / or enhancement of cancer.

Claims

1. A compound, characterized in that it comprises the general formula, wherein: R4 is selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms, substituted alkyl of 1 to 8 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, substituted cycloalkyl of 3 to 8 carbon atoms, aryl, substituted aryl, heteroaryl and substituted heteroaryl; Z is CRZ wherein Rz is selected from the group consisting of halo, hydrogen, 1- to 3-carbon alkyl, 1- to 3-carbon alkoxy, CN, C=NOH, C=NOCH3, C(O)H, C(O)C3-alkyl, 3- to 8-carbon cycloalkyl, heterocyclyl, aryl, heteroaryl, substituted 1- to 3-carbon alkyl, substituted 3- to 8-carbon cycloalkyl, substituted heterocyclyl, substituted aryl, substituted heteroaryl, —B—NRaRb, —B—ORa, —B—C(O)Ra, —B—C(O)ORa, —B—C(O)NRaRa; wherein B is either a bond, a 1- to 3-carbon alkyl, or a branched 1- to 3-carbon alkyl;and each of Ra and Rb is selected independently from the group consisting of hydrogen, alkyl of 1 to 3 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, heterocyclyl, aryl, heteroaryl, substituted alkyl, substituted cycloalkyl, substituted heterocyclyl, substituted aryl, and substituted heteroaryl; and n is an integer from 9 to 20.

2. The compound according to claim 1, characterized in that n is an integer from 12 to 20.

3. The compound according to claim 2, characterized in that R4 is cyclopentyl and Z is dimethylcarboxamide.

4. The compound according to claim 1, characterized in that the compound comprises the general formula ML / Ί where U represents an integer from 9 to 20.

5. The compound according to claim 4, characterized in that n is an integer from 12 to 20.

6. The compound according to claim 4, characterized in that n is 12.

7. A pharmaceutical composition, characterized in that it comprises a compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition according to claim 7, characterized in that the composition is a tablet comprising a core having between 35% and 55% by weight of the compound of any of claims 1 to 6, and a pharmaceutically acceptable carrier.

9. The pharmaceutical composition according to claim 8, characterized in that the pharmaceutically acceptable carrier comprises microcrystalline cellulose, crospovidone type A, low-substituted hydroxypropylcellulose, magnesium stearate, and colloidal anhydrous silica.

10. A method for treating cancer, the method being characterized in that it comprises administering to a patient in need thereof, a pharmaceutically effective amount of the compound according to any of claims 1 to 6 or the pharmaceutical composition according to any of claims 7 to 9.

11. A method for treating or preventing metastatic diseases, the method being characterized in that it comprises administering to a patient in need thereof, a pharmaceutically effective amount of the compound according to any of claims 1 to 6 or the pharmaceutical composition according to any of claims 7 to 9.

12. A method for treating or preventing tumor recurrence, the method being characterized in that it comprises administering to a patient in need thereof, a pharmaceutically effective amount of the compound according to any of claims 1 to 6 or the pharmaceutical composition according to any of claims 7 to 9.

13. A method for reducing resistance to cancer treatment, the method being characterized in that it comprises administering to a patient in need thereof, a pharmaceutically effective amount of the compound according to any of claims 1 to 6 or the pharmaceutical composition according to any of claims 7 to 9.

14. A method for treating or preventing at least one of the resistances to radiation therapy, resistance to chemotherapy, and resistance to hormone therapy, the method being characterized in that it comprises administering to a patient in need thereof, a pharmaceutically effective amount of the compound according to any one of claims 1 to 6 or the pharmaceutical composition according to any one of claims 7 to 9.

15. A method for preventing or reducing the proliferation of at least one of the cancer cells, cancer stem cells, and circulating tumor cells, the method being characterized in that it comprises administering to a patient in need thereof, a pharmaceutically effective amount of the compound according to any one of claims 1 to 6 or the pharmaceutical composition according to any one of claims 7 to 9.

16. The use of the compound according to any of claims 1 to 6, in the manufacture of a medicament for the treatment of cancer.

17. The use of the compound according to any of claims 1 to 6, in the manufacture of a medicament for the treatment of cancer.

18. The use of the compound according to any of claims 1 to 6, in the manufacture of a medicament for the treatment of a metaphasic disease.