Fgfr inhibitor for use in the treatment of hypophosphatemic disorders

Abstract

The present invention relates generally to 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimid-4-yl}-1-methyl-urea or a pharmaceutically acceptable salt or solvate thereof or a pharmaceutical composition comprising 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimid-4-yl}-1-methyl-urea or a pharmaceutically acceptable salt or solvate thereof for use in the treatment of X-linked hypophosphatemic rickets (XLH), autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets (ARHR), tumor-induced osteomalacia, post-renal transplant hypophosphatemia, epidermal nevus syndrome, osteoglophonic dysplasia or McCune-Albright syndrome.

1 . A method of treating a disease selected from the group consisting of post-renal transplant hypophosphatemia, epidermal nevus syndrome, osteoglophonic dysplasia and McCune-Albright syndrome, the method comprising administering to a patient a therapeutically effective amount of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-(6[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimid-4-ul)-1-methyl-urea, or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The method of  claim 1 , wherein 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-(6[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimid-4-ul)-1-methy1-urea is present as a monophosphoric acid salt. 
     
     
         3 . The method of  claim 2 , wherein the amount of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimid-4-yl}-1-methyl-urea monophosphoric acid salt is about 1 mg- 50 mg. 
     
     
         4 . The method of  claim 2 . wherein the amount of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimid-4-yl}-1-methyl-urea monophosphoric acid salt is about 1 mg-25 mg. 
     
     
         5 . The method of  claim 2 , further comprising administering to the patient another FGFR inhibitor, phosphate, calcium, osteopontin (OPN), parathyroid hormone or its analogue (PTH), or vitamin D or vitamin D analogue. 
     
     
         6 . The method of  claim 1 , wherein 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-(6[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimid-4-ul)-1-methyl-urea is present as a free base.