Patent ID: 6221334
Filing Date: 2001-04-24
Classification: A61K,A61P

Abstract:
A composition comprising folate-receptor binding ligands and a pharmaceutically acceptable carrier, said folate-receptor binding ligands comprising dendrimeric first-generation conjugates containing one folate-receptor binding moiety coupled to one or more macrocyclic metal-chelating ligand radicals that are optionally chelated to paramagnetic, superparamagnetic, radioactive or non-radioactive metals for detection outside the body by imaging means for diagnosis or for providing a therapeutic or radiotherapeutic effect; wherein said folate-receptor binding ligands have the structure of formulae ##STR56##wherein R.sub.0 is a folate-receptor moiety of formula: ##STR57##wherein for the first generation dendrimers of formula VIIa, bearing one folate-receptor binding moiety and 3 or 6 metal chelating ligand radicals:W.sub.1 and W.sub.2 are each independently --OR'"", --SR'"", --NR'""R'"" --CON(R.sub.2).sub.2, -glutamate, -polyglutamate, or -K.sub.6 ;wherein each -R'"" is independently --H, -alkyl or -hydroxyalkyl;with the proviso that either W.sub.1, W.sub.2, or both W.sub.1 and W.sub.2 of formula VIIa must be -K.sub.6, where -K.sub.6 is a moiety of formula VIIIa: ##STR58##whereinY is a single bond;A is --C(.dbd.O)-- or C(.dbd.S);M.sub.1 is a superparamagnetic, paramagnetic, radioactive or non-radioactive metal; andR.sub.1 through R.sub.5 is H;K.sub.1 is a macrocyclic metal chelating ligand of formula VI: ##STR59##whereinQ is --[(CR')(R"")].sub.s1 --[C(t)(R.sub.21)].sub.s2 --[C(R.sub.22)(R.sub.23)].sub.s3 --X.sub.3 --Y--X.sub.4 --;s1 is 0;t is COOH;s2 is 1;s3 is 1;X.sub.3 and Y are independently a single bond;n is 1;R' is H;R"" is methyl;G is COOH; andeach of R.sub.13 through R.sub.23 is independently H;or a pharmaceutically acceptable salt thereof.