Benzimidazole derivatives as ERBB tyrosine kinase inhibitors for the treatment of cancer
Provided herein are benzimidazole derivatives, for example, of Formula I, and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a proliferative disease.
1. A compound selected from:
and single enantiomers, racemic mixtures, mixtures of diastereomers, and isotopic variants thereof; and pharmaceutically acceptable salts, solvates, and prodrugs thereof.
2. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.
3. The pharmaceutical composition of claim 2 , wherein the composition is formulated for oral, nasal, bronchial, or topical administration.
4. The pharmaceutical composition of claim 2 , wherein the composition is formulated as a single dosage form.
5. The pharmaceutical composition of claim 2 , wherein the composition is formulated as oral, parenteral, nasal, respiratory, pulmonary, or intravenous dosage form.
6. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is in an oral dosage form.
7. The pharmaceutical composition of claim 6 , wherein the oral dosage form is a tablet or capsule.
8. The pharmaceutical composition of claim 2 , further comprising a second therapeutic agent.
9. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
10. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
11. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
13. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
14. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
15. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
16. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
17. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
18. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
19. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
20. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
21. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
22. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
23. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
24. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
25. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
26. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
27. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
28. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
29. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
30. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
31. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
32. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
33. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
34. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
35. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
36. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
37. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
38. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
39. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
40. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
41. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
42. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
43. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
44. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
45. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
46. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
47. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
48. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
49. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
50. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.