Substituted benzazoles and methods of their use as inhibitors of raf kinase
AssigneeNovartis AG
InventorsPayman Amiri, Wendy Fantl, Barry Haskell Levine, Daniel J. Poon, Savithri Ramurthy, Paul A. Renhowe, Sharadha Subramanian, Leonard Sung
Life of this patent
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Abstract
New substituted benz-azole compounds, compositions and methods of inhibition of Raf kinase activity in a human or animal subject are provided. The new compounds compositions may be used either alone or in combination with at least one additional agent for the treatment of a Raf kinase mediated disorder, such as cancer.
Claims23
A method of inhibiting Raf kinase activity in a human or animal subject suffering from a Ras/mitogen-activated protein kinase signal pathway-mediated cancer disorder selected from the group consisting of melanoma, breast cancer, prostate cancer, lung cancer, pancreatic cancer, thyroid cancer, bladder cancer, colon cancer, liver cancer, myeloid leukemia, and villous colon adenoma, comprising administering to the human or animal subject a composition comprising an amount of a compound of the formula (II) effective to inhibit Raf kinase activity in the human or animal subject:
- wherein Y is O;
- A1 is substituted monocyclic carbocyclic aryl;
- A2 is pyridyl;
- R1 is taken together with R2 to form a substituted or unsubstituted imidazolyl group, or a substituted or unsubstituted benzimidazolyl group, wherein the dashed line represents a single or double bond;
- R3 is hydrogen;
- and
- R4 is C1-6 alkyl;
- or a pharmaceutically acceptable salt thereof.
A method of inhibiting Raf kinase activity in a human or animal subject suffering from a Ras/mitogen-activated protein kinase signal pathway-mediated hormone dependent cancer disorder selected from the group consisting of breast cancer and prostate cancer, comprising administering to the human or animal subject a composition comprising an amount of a compound of the formula (II) effective to inhibit Raf kinase activity in the human or animal subject:
- wherein Y is O;
- A1 is substituted monocyclic carbocyclic aryl;
- A2 is pyridyl;
- R1 is taken together with R2 to form a substituted or unsubstituted imidazolyl group, or a substituted or unsubstituted benzimidazolyl group, wherein the dashed line represents a single or double bond;
- R3 is hydrogen;
- and
- R4 is C1-6 alkyl;
- or a pharmaceutically acceptable salt thereof.
A method of inhibiting Raf kinase activity in a human or animal subject suffering from a Ras/mitogen-activated protein kinase signal pathway-mediated hematological cancer disorder, comprising administering to the human or animal subject a composition comprising an amount of a compound of the formula (II) effective to inhibit Raf kinase activity in the human or animal subject:
- wherein Y is O;
- A1 is substituted monocyclic carbocyclic aryl;
- A2 is pyridyl;
- R1 is taken together with R2 to form a substituted or unsubstituted imidazolyl group, or a substituted or unsubstituted benzimidazolyl group, wherein the dashed line represents a single or double bond;
- R3 is hydrogen;
- and
- R4 is C1-6 alkyl;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.