Iodinated compounds having radiocontrast properties

Abstract

The present disclosure pertains to iodinated compounds that comprise at least one 2,4,6-triiodobenzene moiety in which at least one of the hydrogens at 1-, 3- and 5-positions of the 2,4,6-triiodobenzene moiety is substituted by an iodinated substituent that comprises one or more iodophenyl-containing groups. The present disclosure also pertains to compositions containing such iodinated compounds and methods of making such iodinated compounds.

1 . A composition comprising one or more iodinated compounds that comprise at least one 2,4,6-triiodobenzene moiety in which at least one of the hydrogens at 1-, 3- and 5-positions of the 2,4,6-triiodobenzene moiety is substituted by an iodinated substituent that comprises one or more iodophenyl-containing groups. 
     
     
         2 . The composition of  claim 1 , wherein the iodinated compounds comprise one or two 2,4,6-triiodobenzene moieties in which at least one of the hydrogens at 1-, 3- and 5-positions of each of the 2,4,6-triiodobenzene moieties is substituted by an iodinated substituent that comprises one or more iodophenyl-containing groups. 
     
     
         3 . The composition of  claim 1 , wherein the one or more iodophenyl-containing groups are selected from one or more of mono-iodophenyl-containing groups, di-iodophenyl-containing groups, tri-iodophenyl-containing groups, tetra-iodophenyl-containing groups or penta-iodophenyl-containing groups. 
     
     
         4 . The composition of  claim 1 , wherein the one or more iodophenyl-containing groups are selected from iodophenyloxy groups, iodophenylcarbonyloxy groups, or iodophenyl groups coupled via a cyclic acetal group or a carbamate group. 
     
     
         5 . The composition of  claim 1 , wherein the iodinated substituent comprises a C 2 -C 6 -alkyl-amino group in which C 2 -C 6 -alkyl hydrogens are substituted by (a) the one or more iodophenyl-containing groups and (b) zero, one or a plurality of hydroxyl groups. 
     
     
         6 . The composition of  claim 1 , wherein the iodinated substituent is a C 2 -C 6 -alkyl-aminocarbonyl group or a C 2 -C 6 -alkyl-carbonylamino group in which C 2 -C 6 -alkyl hydrogens are substituted by (a) the one or more iodophenyl-containing groups and (b) zero, one or a plurality of hydroxyl groups. 
     
     
         7 . The composition of  claim 1 , wherein the C 2 -C 6 -alkyl-aminocarbonyl group is a C 3 -alkyl-aminocarbonyl group. 
     
     
         8 . The composition of any of  claim 1 , wherein a molar ratio of hydroxyl groups to iodophenyl-containing groups ranges from 0:1 to 10:1. 
     
     
         9 . A composition of  claim 1 , further comprising a polymer. 
     
     
         10 . The composition of  claim 9  having a radiopacity ranging from 10-1000 Hounsfield Units (HU). 
     
     
         11 . The composition of  claim 9  having an amount of iodine ranging from 5 to 40 wt % or an amount of iodine ranging from 50-900 mg I/cm 3 . 
     
     
         12 . A medical supply comprising (a) a composition comprising one or more iodinated compounds that comprise at least one 2,4,6-triiodobenzene moiety in which at least one of the hydrogens at 1-, 3- and 5-positions of the 2,4,6-triiodobenzene moiety is substituted by an iodinated substituent that comprises one or more iodophenyl-containing groups and (b) a polymer. 
     
     
         13 . The medical supply of  claim 12 , wherein the medical supply is an embolic composition. 
     
     
         14 . The medical supply of  claim 13 , wherein the embolic composition is a liquid embolic composition. 
     
     
         15 . The medical supply of  claim 12 , wherein the medical supply is a medical device. 
     
     
         16 . The medical supply of  claim 15 , wherein the composition is in the form of a medical device coating. 
     
     
         17 . A method comprising reacting (a) at least one compound that comprises at least one 2,4,6-triiodobenzene moiety in which at least one of the hydrogens at 1-, 3- and 5-positions of the 2,4,6-triiodobenzene moiety is substituted by a polyhydroxylated substituent with (b) a compound of the formula XI, formula XII, or formula XIX 
       
         
           
           
               
               
           
         
         wherein n is 1, 2, 3, 4 or 5, wherein R 81  is selected from —H, —F, —Cl, —Br, —I, anhydride, —OH, an imidazolide, or an O-acylisourea, wherein R 70  is —H or C 1 -C 6  alkyl, wherein m is 0, 1, 2, 3, 4 or 5, wherein X is —O − Na +  when m is 0, and wherein X is —F, —Cl, —Br, or —I when m is 1, 2, 3, 4 or 5, under conditions such a linkage comprising a moiety selected from an ether, an ester, a cyclic acetal or a hemiacetal, is formed. 
       
     
     
         18 . The method of  claim 17 , wherein an ester-containing linkage is formed by carbodiimide coupling, wherein an ether-containing linkage is formed by Williamson synthesis, or wherein a cyclic-acetal-containing linkage or hemiacetal is formed by acetalization of aldehyde or ketone. 
     
     
         19 . The method of  claim 18 , wherein the polyhydroxylated substituent comprises a polyhydroxylated C 2 -C 6 -alkyl group. 
     
     
         20 . The method of  claim 17 , wherein the at least one compound is selected from the following: