Compositions for modulating a kinase cascade and methods of use thereof
The invention relates to compositions comprising 2-(5-(4-(2-morpholinoethoxyl)phenyl)pyridin-2-yl)-N-benzylacetamide and its mesylate and dihydrochloride salts. The invention provides an efficient process for the synthesis of 2-(5-(4-(2-morpholinoethoxyl)phenyl)pyridin-2-yl)-N-benzylacetamide and its mesylate and dihydrochloride salts and methods for modulating one or more components of a kinase cascade using the compositions of the invention. The present invention also provides a novel polymorph of the mesylate salt of 2-(5-(4-(2-morpholinoethoxyl)phenyl)pyridin-2-yl)-N-benzylacetamide (Form A), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure.
1. A polymorph of 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide di-HCl salt, characterized by an X-ray powder diffraction pattern including peaks at about 15.6, 22.7, and 23.5 degrees 2θ.
2. A pharmaceutical composition comprising a polymorph according to claim 1 and a pharmaceutically acceptable excipient or carrier.
3. A method of treating a disease or condition in a subject in need thereof, said method comprising the step of administering to said subject a pharmaceutical composition according to claim 2 , wherein said disease or condition is selected from the group consisting of lung cancer, colon cancer, breast cancer, brain cancer, hearing loss, osteoporosis, obesity, diabetes, ophthalmic diseases, stroke, atherosclerosis, neuropathic pain, hepatitis B, and autoimmune disease.
4. A method of preparing a polymorph according to claim 1 , comprising the step of adding hydrochloric acid to 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide in ethanol.
5. A polymorph of 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide di-HCl salt, characterized by an X-ray powder diffraction pattern including peaks at about 15.6, 17.0, 19.3, 21.8, 22.7, 23.5, 24.6, 26.0, 27.6, and 28.8 degrees 2θ.
6. A pharmaceutical composition comprising a polymorph according to claim 5 and a pharmaceutically acceptable excipient or carrier.
7. A method of treating a disease or condition in a subject in need thereof, said method comprising the step of administering to said subject a pharmaceutical composition according to claim 6 , wherein said disease or condition is selected from the group consisting of lung cancer, colon cancer, breast cancer, brain cancer, hearing loss, osteoporosis, obesity, diabetes, ophthalmic diseases, stroke, atherosclerosis, neuropathic pain, hepatitis B, and autoimmune disease.
8. A method of preparing a polymorph according to claim 5 , comprising the step of adding hydrochloric acid to 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide in ethanol.
9. A polymorph of 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide di-HCl salt, characterized by an X-ray powder diffraction pattern substantially similar to that set forth in FIG. 13 .
10. A pharmaceutical composition comprising a polymorph according to claim 9 and a pharmaceutically acceptable excipient or carrier.
11. A method of treating a disease or condition in a subject in need thereof, said method comprising the step of administering to said subject a pharmaceutical composition according to claim 10 , wherein said disease or condition is selected from the group consisting of lung cancer, colon cancer, breast cancer, brain cancer, hearing loss, osteoporosis, obesity, diabetes, ophthalmic diseases, stroke, atherosclerosis, neuropathic pain, hepatitis B, and autoimmune disease.
12. A method of preparing a polymorph according to claim 9 , comprising the step of adding hydrochloric acid to 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide in ethanol.