Maleate salts of a quinazoline derivative useful as an antiangiogenic agent

Abstract

The present invention relates to AZD2171 maleate salt, to particular crystalline forms of AZD2171 maleate salt, to processes for their preparation, to pharmaceutical compositions containing them as active ingredient, to their use in the manufacture of medicaments for use in the production of antiangiogenic and/or vascular permeability reducing effects in warm-blooded animals such as humans, and to their use in methods for the treatment of disease states associated with angiogenesis and/or increased vascular permeability.

1 - 20 . (canceled) 
     
     
         21 . A method for inhibiting VEGF receptor tyrosine kinase in a warm-blooded animal in need of such treatment which comprises orally administering to said animal an effective amount of a pharmaceutical composition comprising crystalline Form A of 4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline maleate, wherein said warm-blooded animal in need of such treatment has a solid tumor cancer that is recurrent. 
     
     
         22 . The method according to  claim 21 , wherein said cancer is a female reproductive cancer. 
     
     
         23 . The method according to  claim 21 , wherein the daily dose of Form A of 4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline maleate administered to said animal ranges from 0.03 mg/kg to 0.5 mg/kg. 
     
     
         24 . The method according to  claim 21 , further comprising administering at least one additional treatment chosen from surgery, radiotherapy, and chemotherapy. 
     
     
         25 . The method according to  claim 24 , wherein said chemotherapy comprises at least one therapeutic agent chosen from (i) other antiangiogenic agents; (ii) cytostatic agents; and (iii) antiproliferative/antineoplastic drugs. 
     
     
         26 . The method according to  claim 25 , wherein said antiproliferative/antineoplastic drugs are chosen from platinum derivatives.