US 12,269,837 B2
Bifunctional do2pa derivatives, chelates with metallic cations and use thereof
Fatima Oukhatar, Brest (FR); Maryline Beyler, Brest (FR); and Raphaël Tripier, Kersaint-Plabennec (FR)
Assigned to CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS), Paris (FR); and UNIVERSITÉ DE BRETAGNE OCCIDENTALE, Brest (FR)
Filed by CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS), Paris (FR); and UNIVERSITE DE BRETAGNE OCCIDENTALE, Brest (FR)
Filed on Jan. 24, 2022, as Appl. No. 17/648,688.
Application 17/648,688 is a division of application No. 16/579,133, filed on Sep. 23, 2019, granted, now 11,266,754.
Application 16/579,133 is a division of application No. 15/533,204, abandoned, previously published as PCT/EP2015/078732, filed on Dec. 4, 2015.
Claims priority of application No. 14196637 (EP), filed on Dec. 5, 2014.
Prior Publication US 2022/0143230 A1, May 12, 2022
Int. Cl. C07D 401/12 (2006.01); A61K 51/10 (2006.01); C07D 213/79 (2006.01); C07D 257/02 (2006.01); C07D 401/06 (2006.01); C07F 7/24 (2006.01); C07F 9/6524 (2006.01); C07F 9/94 (2006.01)
CPC C07F 9/94 (2013.01) [A61K 51/1093 (2013.01); C07D 213/79 (2013.01); C07D 257/02 (2013.01); C07D 401/06 (2013.01); C07D 401/12 (2013.01); C07F 7/24 (2013.01); C07F 9/6524 (2013.01); A61K 2123/00 (2013.01)] 15 Claims
 
1. A chelate resulting from the complexation of a ligand of formula (Ia)

OG Complex Work Unit Chemistry
or a basic salt thereof;
wherein
R1 and R1′ each independently represents:
a hydrogen atom;
a coupling function, wherein the coupling function is selected from the group consisting of amine; isothiocyanate; isocyanate;
N-hydroxysuccinimide ester, N-hydroxyglutarimide ester, maleimide ester; carboxylic acid; acid anhydride, acid halide; alcohol; alkyne; halide; azide; siloxy; phosphonic acid; thiol; tetrazine; norbornen; oxoamine; aminooxy; thioether; haloacetamide; glutamate; glutaric anhydride, succinic anhydride, maleic anhydride; aldehyde; ketone; hydrazide; chloroformate; and maleimide; or
a bioactive group, wherein the bioactive group is a peptide;
L1 and L1′ each independently represents:
a single bond; or
a linker selected from the group consisting of alkyl, aryl, arylalkyl, alkylaryl, heteroaryl, heteroarylalkyl, alkylheteroaryl, alkenyl, and alkynyl; wherein alkyl moieties are optionally interrupted by one or more heteroatoms selected from the group consisting of O, N, and S; optionally additionally comprising a residue of a coupling function through which R1 and R1′ are bounded to L1, and L1′ respectively;
provided that at least one of -L1-R1 and-L1′-R1′ represents a linker with a coupling function or a linker with a bioactive group;
with a metallic cation selected from the group consisting of bismuth (III), lead (II), copper (II), copper (I), gallium (III), zirconium (IV), technetium (III), indium (III), rhenium (VI), astatine (III), yttrium (III), samarium (III), actinium (III), lutetium (III), terbium (III), holmium (III), gadolinium (III), europium (III), and 212Bi(212Pb).