Inventors:
Dangshe Ma - Millwood NY, US
Michael McDevitt - Bronx NY, US
David Scheinberg - New York NY, US
Jaime Simon - Angleton TX, US
Garry Kiefer - Lake Jackson TX, US
R. Frank - Lake Jackson TX, US
Gyongyi Gulyas - Lake Jackson TX, US
International Classification:
A61K051/00
C07F005/00
US Classification:
424/001650, 534/011000, 540/474000
Abstract:
Actinium-225 (Ac) complexes with functionalized chelants of the formula (I) wherein; each Q is independently hydrogen or ((CHR)COR; Qis hydrogen or (CHR)COR; each R independently is hydrogen, benzyl or C-Calkyl; with the proviso that at least two of the sum of Q and Qmust be other than hydrogen, each Rindependently is hydrogen; C-Calkyl or (C-Calkyl)phenyl; X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon—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 carbon to 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 (1) wherein s is an integer of 0 or 1; t is an integer of 0 to 20 inclusive; Ris an electrophilie or nucleophilic moiety which allows for covalent attachment to an antibody or fragment thereof, or synthetic linker which can be attached to an antibody or fragment thereof, 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 an antibody or antibody fragment; with the proviso that when s, t, m, r, and n are 0, then Ris other than carboxyl; their pharmaceutically acceptable salts, their conjugates and the use thereof for radioimmunotherapy is disclosed.
