Treatment of brain cancer

Abstract

Compounds for the treatment of brain cancer are provided herein. Pharmaceutical compositions comprised of those compounds for the treatment of brain cancer are also provided herein.

What is claimed is: 
     
         1 - 17 . (canceled) 
     
     
         18 . A method of treating local or metastatic brain cancer that is caused by ErbB2 over-expression or amplification in a mammal comprising administering a therapeutically effective amount of N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine or (2-((4-((4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)amino)-4-methyl-4,5-dihydrooxazol-4-yl)methanol to the mammal. 
     
     
         19 . A method of treating local or metastatic brain cancer that is caused by ErbB2 over-expression or amplification in a patient having brain cancer comprising administering a therapeutically effective amount of N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine or (2-((4-((4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)amino)-4-methyl-4,5-dihydrooxazol-4-yl)methanol to the patient. 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 18 , wherein the N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine or (2-((4-((4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)amino)-4-methyl-4,5-dihydrooxazol-4-yl)methanol is administered as an oral dosage form. 
     
     
         22 . The method of  claim 18 , wherein the N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine or (2-((4-((4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)amino)-4-methyl-4,5-dihydrooxazol-4-yl)methanol is in a tablet. 
     
     
         23 . The method of  claim 18 , wherein the method includes another therapeutic agent. 
     
     
         24 . The method of  claim 23 , wherein the therapeutic agent is selected from trastuzumab, capecitabine, bevacizumab, paclitaxel and docetaxel. 
     
     
         25 . The method of  claim 18 , wherein the method is used after previous treatment for brain cancer. 
     
     
         26 . The method of  claim 25 , wherein the previous treatment for brain cancer is selected from surgery, radiation therapy and chemotherapy or mixtures thereof. 
     
     
         27 . The method of  claim 25 , wherein the previous treatment for brain cancer is selected from surgery, conventional external radiation therapy, three-dimensional conformal radiation therapy, intensity modulated radiation therapy, stereotactic radiosurgery, fractionated stereotactic radiation therapy, proton radiation therapy, internal or implant radiation therapy, temozolomide, bevacizumab, carmustine, lomustine, procarbazine, vincristine, tumor treating fields therapy, everolimus, procarbazine, lomustine, cisplatin, carboplatin and methotrexate or mixtures thereof. 
     
     
         28 . The method of  claim 18 , wherein the method is used after previous treatment for breast cancer. 
     
     
         29 . The method of  claim 28 , wherein the previous treatment for breast cancer is selected from surgery, sentinel lymph node biopsy followed by surgery, radiation therapy, chemotherapy, hormone therapy and targeted therapy. 
     
     
         30 . The method of  claim 28 , wherein the previous treatment for breast cancer is selected from lumpectomy, partial mastectomy, segmental mastectomy, total mastectomy, modified radical mastectomy, external radiation, internal radiation, methotrexate, paclitaxel albumin-stabilized nanoparticle formulation, ado-trastuzumab emtansine, doxorubicin, fluorouracil, everolimus, anastrozole, exemestane, capecitabine, cyclophosphamide, docetaxel, epirubicin, exemestane, toremifene, fulvestrant, letrozole, gemcitabine, trastuzumab, ixabepilone, lapatinib, tamoxifen, pertuzumab and toremifene, or mixtures thereof. 
     
     
         31 . The method of  claim 18 , wherein N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is administered. 
     
     
         32 . The method of  claim 31 , wherein about 550 to about 650 mg twice per day of N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is administered. 
     
     
         33 . The method of  claim 18 , wherein (2-((4-((4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)amino)-4-methyl-4,5-dihydrooxazol-4-yl)methanol is administered. 
     
     
         34 . The method of  claim 33 , wherein about 25 to about 1800 mg per day of (2-((4-((4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)amino)-4-methyl-4,5-dihydrooxazol-4-yl)methanol is administered. 
     
     
         35 . (canceled) 
     
     
         36 . The method of  claim 19 , wherein the N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine or (2-((4-((4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)amino)-4-methyl-4,5-dihydrooxazol-4-yl)methanol is administered as an oral dosage form. 
     
     
         37 . The method of  claim 19 , wherein the N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine or (2-((4-((4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)amino)-4-methyl-4,5-dihydrooxazol-4-yl)methanol is in the form of a tablet. 
     
     
         38 . The method of  claim 19 , wherein the method includes another therapeutic agent. 
     
     
         39 . The method of  claim 38 , wherein the therapeutic agent is selected from trastuzumab, capecitabine, bevacizumab, paclitaxel and docetaxel. 
     
     
         40 . The method of  claim 19 , wherein the use is after previous treatment for brain cancer. 
     
     
         41 . The method of  claim 40 , wherein the previous treatment for brain cancer is selected from surgery, radiation therapy and chemotherapy or mixtures thereof. 
     
     
         42 . The method of  claim 40 , wherein the previous treatment for brain cancer is selected from surgery, conventional external radiation therapy, three-dimensional conformal radiation therapy, intensity modulated radiation therapy, stereotactic radiosurgery, fractionated stereotactic radiation therapy, proton radiation therapy, internal or implant radiation therapy, temozolomide, bevacizumab, carmustine, lomustine, procarbazine, vincristine, tumor treating fields therapy, everolimus, procarbazine, lomustine, cisplatin, carboplatin and methotrexate or mixtures thereof. 
     
     
         43 . The method of  claim 19 , wherein the use is after previous treatment for breast cancer. 
     
     
         44 . The method of  claim 43 , wherein the previous treatment for breast cancer is selected from surgery, sentinel lymph node biopsy followed by surgery, radiation therapy, chemotherapy, hormone therapy and targeted therapy. 
     
     
         45 . The method of  claim 43 , wherein the previous treatment for breast cancer is selected from lumpectomy, partial mastectomy, segmental mastectomy, total mastectomy, modified radical mastectomy, external radiation, internal radiation, methotrexate, paclitaxel albumin-stabilized nanoparticle formulation, ado-trastuzumab emtansine, doxorubicin, fluorouracil, everolimus, anastrozole, exemestane, capecitabine, cyclophosphamide, docetaxel, epirubicin, exemestane, toremifene, fulvestrant, letrozole, gemcitabine, trastuzumab, ixabepilone, lapatinib, tamoxifen, pertuzumab and toremifene, or mixtures thereof. 
     
     
         46 . The method of  claims 19 , wherein N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is administered. 
     
     
         47 . The method of  claim 46 , wherein about 550 to about 650 mg twice per day of N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is administered. 
     
     
         48 . The method of  claim 19 , wherein (2-((4-((4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)amino)-4-methyl-4,5-dihydrooxazol-4-yl)methanol is administered. 
     
     
         49 . The method of  claim 48 , wherein about 25 to about 1800 mg per day of (2-((4-((4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)amino)-4-methyl-4,5-dihydrooxazol-4-yl)methanol is administered. 
     
     
         50 - 62 . (canceled) 
     
     
         63 . A method of treating local or metastatic brain cancer that is caused by ErbB2 over-expression or amplification using (2-((4-((4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)amino)quinazolin-6-yl)amino)-4-methyl-4,5-dihydrooxazol-4-yl)methanol in a patient having brain cancer comprising administering an effective amount of N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine to the patient. 
     
     
         64 . (canceled) 
     
     
         65 . The method of  claim 63 , wherein the N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is administered as an oral dosage form. 
     
     
         66 . The method of  claim 65 , wherein the N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is in a tablet. 
     
     
         67 . The method of  claim 63 , wherein the method includes another therapeutic agent. 
     
     
         68 . The method of  claim 67 , wherein the therapeutic agent is selected from trastuzumab, capecitabine, bevacizumab, paclitaxel and docetaxel. 
     
     
         69 . The method of  claim 63 , wherein the method is used after previous treatment for brain cancer. 
     
     
         70 . The method of  claim 69 , wherein the previous treatment for brain cancer is selected from surgery, radiation therapy and chemotherapy or mixtures thereof. 
     
     
         71 . The method of  claim 69 , wherein the previous treatment for brain cancer is selected from surgery, conventional external radiation therapy, three-dimensional conformal radiation therapy, intensity modulated radiation therapy, stereotactic radiosurgery, fractionated stereotactic radiation therapy, proton radiation therapy, internal or implant radiation therapy, temozolomide, bevacizumab, carmustine, lomustine, procarbazine, vincristine, tumor treating fields therapy, everolimus, procarbazine, lomustine, cisplatin, carboplatin and methotrexate or mixtures thereof. 
     
     
         72 . The method of  claim 63 , wherein the method is used after previous treatment for breast cancer. 
     
     
         73 . The method of  claim 72 , wherein the previous treatment for breast cancer is selected from surgery, sentinel lymph node biopsy followed by surgery, radiation therapy, chemotherapy, hormone therapy and targeted therapy. 
     
     
         74 . The method of  claim 72 , wherein the previous treatment for breast cancer is selected from lumpectomy, partial mastectomy, segmental mastectomy, total mastectomy, modified radical mastectomy, external radiation, internal radiation, methotrexate, paclitaxel albumin-stabilized nanoparticle formulation, ado-trastuzumab emtansine, doxorubicin, fluorouracil, everolimus, anastrozole, exemestane, capecitabine, cyclophosphamide, docetaxel, epirubicin, exemestane, toremifene, fulvestrant, letrozole, gemcitabine, trastuzumab, ixabepilone, lapatinib, tamoxifen, pertuzumab and toremifene, or mixtures thereof. 
     
     
         75 . The method of  claim 63 , wherein about 550 to about 650 mg twice per day of N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is administered.