Pyrido[2,3-b]pyrazin-8-substituted compounds and their use

摘要

The present invention pertains generally to the field of therapeutic compounds for treating proliferative disorders, cancer, etc., and more specifically to certain pyrido[2,3-b]pyrazin-8-substituted compounds, as described herein, which, inter alia, inhibit RAF (e.g.,B-RAF) activity. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., BRAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and disorders that are ameliorated by the inhibition of RAF, RTK, etc., proliferative disorders such as cancer (e.g., colorectal cancer, melanoma), etc.

主权项

1. A method of inhibiting the progress of, reducing the rate of progress of, alleviating a symptom of, or ameliorating cancer comprising administering to a subject in need of treatment a therapeutically-effective amount of a compound of the following formula, or a pharmaceutically acceptable salt thereof:wherein:
—RPH1 is independently —F or —SMe; and —RPY1 is independently phenyl or pyridyl, and is optionally substituted with one or more substituents selected from —F, —Cl, —Br, —I, —R5, —OH, —OR5, —CF3, —OCF3, wherein each —R5 is independently saturated aliphatic C1-4alkyl;and wherein the cancer is:
thyroid cancer; melanoma (including malignant melanoma); lung cancer (including non-small cell lung cancer and small cell lung cancer); colorectal cancer; pancreatic cancer; sarcoma; gastrointestinal cancer; ovarian cancer; lymphoma; leukemia; skin cancer; testicular cancer; prostate cancer; a carcinoma of the cervix; bladder cancer; breast cancer; liver cancer; kidney cancer; stomach cancer; endometrial cancer; seminoma; a hematopoietic tumor of myeloid lineage; myelodisplastic syndrome; a carcinoma of the oesophagus; brain cancer; glioma; bone cancer; or squamous cancer.