Patent ID: 6670456
Filing Date: 2003-12-30
Classification: A61K,A61P

Abstract:
An Actinium-225 complex comprising a functionalized polyazamacrocyclic chelant compound of the formula I, hereinbelow: G is independently hydrogen or each Q is independently hydrogen, (CHR5)pCO2R or (CHR5)pPO3R6R7 or Q1 is hydrogen, (CHR5)wCO2R or (CHR5)wPO3R6R7; each R is independently hydrogen, benzyl or C1-C4 alkyl; R6 and R7 are independently H, C1-C6 alkyl or (C1-C2 alkyl) phenyl; each R5 is independently hydrogen; C1-C4 alkyl or (C1-C2 alkyl) phenyl; with the proviso that at least two of the sum of Q and Q1 must be other than hydrogen; A is CH, N, Câ€”Br, Câ€”Cl, Câ€”SO3H, Câ€”OR8, Câ€”OR9N+â€”R0Xâˆ’, or Z and Z1 independently are CH, N, Câ€”SO3H, N+â€”R10Xâˆ’, Câ€”CH2â€”OR8 or Câ€”C(O)â€”R11; R8 is H, C1-C5 alkyl, benzyl, or benzyl substituted with at least one R12; R9 is C1-C16 alkylamino; R10 is C1-C16 alkyl, benzyl, or benzyl substituted with at least one R12; R11 is â€”Oâ€”(C1-C3 alkyl), OH or NHR13; R12 is H, NO2, NH2, isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetamido or carboxyl; R13 is C1-C5 alkyl; X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbonâ€”carbon bond; n is 0 or 1; m is an integer from 0 to 10 inclusive; p is 1 or 2; r is 0 or 1; w is 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbonâ€”carbon bond, and the sum of r and w is 0 or 1; L is a linker/spacer group covalently bonded to, and replaces one hydrogen atom of one of the carbon atoms to which it is joined, said linker/spacer group being represented by the formula wherein: s is an integer of 0 or 1; t is an integer of 0 to 20 inclusive; R1 is H or an electrophilic or nucleophilic moiety which allows for covalent attachment to a biological carrier, or synthetic linker which can be attached to a biological carrier, or precursor thereof; and Cyc represents a cyclic aliphatic moiety, aromatic moiety, aliphatic heterocyclic moiety, or aromatic heterocyclic moiety, each of said moieties optionally substituted with one or more groups which do not interfere with binding to a biological carrier; with the proviso that when R1 is H, the linkage to the biological carrier is through one of Q or Q1; and with the proviso that when R1 is other than H, at least one of Q and Q1 must be (CHR5)pPO3R6R7; and with further proviso that when Q is (CHR5)pCO2R, Q1 is (CHR5)wCO2R, R is H, R5 is H, and R1 is H, then the sum of m, n, p, r, s, t, and w is greater than 1; or pharmaceutically acceptable salt thereof; complexed with 225Ac.