4-[4-(amino)-3-fluorophenoxy]-n-methylpyridine-2-carboxamide monohydrate

Abstract

The present invention relates to 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide monohydrate, to processes for its preparation, to pharmaceutical compositions comprising it and to its use in the control of disorders.

1 . (canceled) 
     
     
         2 . The compound of the formula (II) 
       
         
           
           
               
               
           
         
         which shows in the X-ray diffractometry a peak maximum of the 2 Theta angle of 21.2. 
       
     
     
         3 . The compound of  claim 2  which shows in the FIR spectrum a peak maximum of 353 cm −1 . 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . A pharmaceutical composition comprising a compound of  claim 2  and one or more pharmaceutically suitable excipients for the treatment of solid tumors, lymphomas, sarcomas, leukaemia's, cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid and/or parathyroid. 
     
     
         8 . A method for the treatment of a hyper-proliferative disorder comprising administering an effective amount of a pharmaceutical composition of  claim 7  to a subject in need thereof. 
     
     
         9 . The method of  claim 8  wherein the hyper-proliferative disorder to be treated is a solid tumor, lymphoma, sarcoma, leukaemia tumors, cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid and/or parathyroid. 
     
     
         10 . A pharmaceutical composition comprising the compound of the formula (II) 
       
         
           
           
               
               
           
         
       
       and
 the compound of the formula (I) 
 
       
         
           
           
               
               
           
         
         in the polymorph I form having a melting point of 186°-206° C. 
         and one or more inert, nontoxic, pharmaceutically suitable excipients. 
       
     
     
         11 . The pharmaceutical composition of  claim 10  containing more than 90 percent by weight of the compound of the formula (II) related to the total amount of the compound of the formula (II) and formula (I) present in the composition. 
     
     
         12 . The pharmaceutical composition of  claim 10  for the treatment of hyper-proliferative disorders. 
     
     
         13 . A method for treating hyper-proliferative disorders using an effective amount of the a pharmaceutical composition as defined in  claim 10 . 
     
     
         14 . A combination comprising the compound of the formula (II) of  claim 2  and one or more other pharmaceutical agents. 
     
     
         15 . The combination of  claim 14  wherein the one or more other pharmaceutical agents are cytotoxic agents, signal transduction inhibitors, anti-cancer agents, or antiemetics. 
     
     
         16 . The pharmaceutical composition of  claim 10  comprising one or more other pharmaceutical agents. 
     
     
         17 . The pharmaceutical composition of  claim 16  wherein the one or more other pharmaceutical agents are anti-hyper-proliferative agents, cytotoxic agents, signal transduction inhibitors, anti-cancer agents and/or antiemetics. 
     
     
         18 . A pharmaceutical composition of  claim 10  for the treatment of solid tumors, lymphomas, sarcomas, leukemias, cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid and/or parathyroid. 
     
     
         19 . A method of  claim 13  wherein the hyper-proliferative disorder to be treated is a solid tumor, lymphoma, sarcoma, leukemia, cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid and/or parathyroid. 
     
     
         20 . A pharmaceutical composition comprising a compound of  claim 2  of the formula (II) and a pharmaceutically suitable excipient for the treatment of tumors of the digestive tract. 
     
     
         21 . A pharmaceutical composition comprising a compound of  claim 2  of the formula (II) and a pharmaceutically suitable excipient for the treatment of colorectal cancer. 
     
     
         22 . A method for the treatment of tumors of the digestive tract comprising administering an effective amount of a pharmaceutical composition of  claim 20  to a subject in need thereof. 
     
     
         23 . A method for the treatment of colorectal cancer comprising administering an effective amount of a pharmaceutical composition of  claim 21  to a subject in need thereof. 
     
     
         24 . A pharmaceutical composition of  claim 10  for the treatment of tumors of the digestive tract. 
     
     
         25 . A pharmaceutical composition of  claim 10  for the treatment of colorectal cancer. 
     
     
         26 . A method for the treatment of tumors of the digestive tract comprising administering an effective amount of a pharmaceutical composition of  claim 24  to a subject in need thereof. 
     
     
         27 . A method for the treatment of colorectal cancer comprising administering an effective amount of a pharmaceutical composition of  claim 25  to a subject in need thereof.