US 7,579,373 B2
Targeted bisplatinum polyamines as pro-drugs: selective release of platinum
Nicholas Farrell, Richmond, Va. (US); Alexander Hegmans, Kingston (Canada); and John D. Roberts, Richmond, Va. (US)
Assigned to Virginia Commonwealth University, Richmond, Va. (US)
Filed on Aug. 22, 2002, as Appl. No. 10/225,436.
Prior Publication US 2003/0114433 A1, Jun. 19, 2003
Int. Cl. A61K 31/27 (2006.01); A61K 31/28 (2006.01); C07F 15/00 (2006.01)
U.S. Cl. 514—478  [514/483; 514/492; 556/137] 61 Claims
 
1. A linear polyamine-bridged platinum compound having the general formula
[(PtXYZ)-A-(Pt X′Y′Z′)], or salts thereof, where X, Y, Z, X′, Y′, and Z′ may be the same or different and are
anionic groups, or
neutral groups which may be substituted or unsubstituted; and
A is a bridging polyamine having a general formula selected from the group consisting of
H2N(CH2)xNBB′(CH2)yNH2 where x ranges from 1 to 10 and y ranges from 1 to 10, or
H2N(CH2)xNBB′(CH2)yNBB′(CH2)xNH2 where x ranges from 1 to 10 and y ranges from 1 to 10,
where B and B′ are hydrogen or a labile blocking group and may be the same or different, and may be the same or different at each location, and where B′ may be present or absent,
and wherein when said anionic groups or neutral groups of said linear polyamine-bridged platinum compound are in a 1,1/t,t configuration with respect to said bridging polyamine, said labile blocking group is not tBOC;
and wherein
i) said anionic groups are selected from the group consisting of halide, pseudohalide, substituted pseudohalide, sulphate, phosphate, phosphonate, nitrate, carboxylate, substituted carboxylate, dicarboxylate, and substituted dicarboxylate;
ii) said neutral groups are selected from the group consisting of ammonia, primary or secondary amines, a “dangling” diamine H2N(CH2)nNBB′ where only the —NH2 moiety is bound to platinum, pyridine, substituted pyridine, quinoline, imidazole, thiazole, pyrimidine, purine, acridine, pyrazole, benzimidazole, and benzothiazole; and for 1,1/c,c configurations, Y, Y′, Z and Z′ may be a chelating bidentate diamine; and
iii) said labile blocking group is an amide protection group,
with the proviso that when x =4, y =3, and at least two of X, Y, Z and X′, Y′, Z′ are NH3, one of B or B′ is a labile protecting group.