Use of derivatives containing c-o-p bonds in patients with kidney failure

Abstract

Use of a derivative containing C—O—P bonds in a controlled release form to treat patients with kidney failure. Moreover, it comprises the use of said derivatives together with other active substances, which particularly may be selected from a list comprising a calcimimetic, vitamin, phosphate binder, thiosulfate, bisphosphonate, pyrophosphate, citrate, diuretic, antihypertensive and anticholesteraemic agent.

1 . A method for the treatment and/or prevention of a kidney failure-related disease in a subject with kidney failure comprising administering to a subject in need an effective amount of a medicament which comprises at least one compound of formula I, or a pharmaceutical acceptable salt thereof: 
       
         
           
           
               
               
           
         
         where: 
         each R 1  to R 12  independently represents H, —X, —OX, —NHX, —SX, —OSO 3 HX, —OSO 3 X 2  or a compound of formula II: 
       
       
         
           
           
               
               
           
         
         where each X independently represents H, C 1-30 alkyl, C 2-30 alkenyl, C 2-30 alkynyl or Cy 1 , where C 1-30 alkyl, C 2-30 alkenyl and C 2-30 alkynyl are independently optionally substituted by one or more R 14  and where Cy 1  is optionally substituted by one or more R 15 ; 
         Cy 1  represents a carbocyclic or heterocyclic three- to 10-membered ring, which may be saturated, partially unsaturated or aromatic, where said heterocycle has between one and four heteroatoms selected from amongst O, S and N, where said ring can be bound to the rest of the molecule via any available C atom and where Cy 1  optionally fused to between one and four five- or six-membered rings, each saturated, partially unsaturated or aromatic, carbocyclic or heterocyclic, and where said fused heterocycle may contain one or two heteroatoms selected from amongst O, N and S; 
         each R 13  independently represents H, C 1-30 alkyl, —NH 2 , —NHC 1-30 alkyl or —N(C 1-30 alkyl) 2 , where each C 1-30 alkyl is independently optionally substituted with one or more halogen, —OH, —CN and —NO 2  groups; and 
         each R 14  and R 15  independently represents —OH, C 1-30 alkoxy, C 1-30 alkylthionyl, C 1-30 acyloxy, phosphate, halogen, trihaloC 1-30 alkyl, nitrile or azide, 
         with the condition that at least one of R 1  to R 12  independently represents a compound of formula II, 
         characterised in that said medicament is administered in a prolonged release form. 
       
     
     
         2 . The method according to  claim 1 , where:
 each X independently represents H, C 1-30 alkyl or Cy 1 , where C 1-30 alkyl is optionally substituted by one or more R 14  and where Cy 1  is optionally substituted by one or more R 15 ; and   each R 14  and R 15  independently represents —OH, C 1-30 alkoxy, C 1-30 alkylthionyl, C 1-30 acyloxy, phosphate, halogen, trihaloC 1-30 alkyl, nitrile or azide.   
     
     
         3 . The method according to  claim 1 , where:
 each X represents H, C 1-30 alkyl or Cy 1 .   
     
     
         4 . The method according to  claim 1 , where:
 each X represents H.   
     
     
         5 . The method according to  claim 1 , where:
 At least one of radicals R 1 , R 3 , R 5 , R 7 , R 9  and R 11  independently represents a compound of formula II:   
       
         
           
           
               
               
           
         
         where each R 13  independently represents H, C 1-30 alkyl, —NH 2 , —NHC 1-30 alkyl or —N(C 1-30 alkyl) 2 , where each C 1-30 alkyl is independently optionally substituted by one or more halogen, —OH, —CN and —NO 2  groups; and 
         R 2 , R 4 , R 6 , R 8 , R 10  and R 12  independently represent H. 
       
     
     
         6 . The method according to  claim 1 , where:
 R 1 , R 3 , R 5 , R 7 , R 9  and R 11  independently represent a compound of formula II:   
       
         
           
           
               
               
           
         
         each R 13  independently represents H or C 1-30 alkyl, where each C 1-30 alkyl is independently optionally substituted by one or more halogen, —OH, —CN and —NO 2  groups; and 
         R 2 , R 4 , R 6 , R 8 , R 10  and R 12  independently represent H. 
       
     
     
         7 . The method according to  claim 1 , where:
 R 1 , R 3 , R 5 , R 7 , R 9  and R 11  independently represent a compound of formula II:   
       
         
           
           
               
               
           
         
         each R 13  independently represents H or C 1-30 alkyl; and 
         R 2 , R 4 , R 6 , R 8 , R 10  and R 12  independently represent H. 
       
     
     
         8 . The method according to  claim 1 , where:
 R 1 , R 3 , R 5 , R 7 , R 9  and R 11  independently represent a compound of formula II:   
       
         
           
           
               
               
           
         
         each R 13  independently represents H; and 
         R 2 , R 4 , R 6 , R 8 , R 10  and R 12  independently represent H. 
       
     
     
         9 . A method for the treatment and/or prevention of a kidney failure-related disease in a subject with kidney failure comprising administering to a subject in need an effective amount of a medicament which comprises a composition comprising at least one compound of general formula I as described in  claims 1  to  8  and another active substance characterised in that said medicament is administered in a prolonged release form. 
     
     
         10 . The method according to  claim 9 , where the active substance is selected from a list comprising a calcimimetic, vitamin, phosphorus chelator, thiosulfate, bisphosphonate, pyrophosphate, citrate, diuretic, antihypertensive and anticholesteraemic agent. 
     
     
         11 . A method for the treatment and/or prevention of a kidney failure-related disease in a subject with kidney failure comprising administering to a subject in need an effective amount of a medicament which comprises a combined preparation composing at least one compound of general formula I as described in  claims 1  to  8  and a compound selected from a list comprising a calcimimetic, vitamin B, vitamin D or vitamin K, phosphorus chelator, thiosulfate, bisphosphonate, pyrophosphate, citrate, diuretic, antihypertensive and anticholesteraemic agent separately, simultaneously or sequentially. 
     
     
         12 . The method according to any of  claims 1 ,  9  or  11 , where the kidney failure-related diseases are calcium disorder-related diseases. 
     
     
         13 . The method according to any of  claims 1 ,  9  or  11 , where the calcium disorder-related diseases are selected from the list comprising renal lithiasis, cardiovascular calcification, cardiovascular disease, osteoporosis, bone cancer, podagra, calcific tendinitis, calcinosis cutis, rheumatoid arthritis, bone mineral disease, osteomalacia, adynamic bone, calciphylaxis and cardiovascular diseases. 
     
     
         14 . The method according to any of  claims 1 ,  9  or  11 , where the medicinal product is found in a form suitable for parenteral, topical or enteral administration.