US 12,103,927 B2
Pyclen-based macrocyclic ligands, chelates thereof and uses thereof
Nadège Hamon, Brest (FR); Maryline Beyler, Brest (FR); Raphaël Tripier, Kersaint-Plabennec (FR); Olivier Maury, Brindas (FR); and Janah Shaya, Lyons (FR)
Assigned to CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE, Paris (FR); ÉCOLE NORMALE SUPÉRIEURE DE LYON, Lyons (FR); UNIVERSITÉ CLAUDE BERNARD LYON 1 (UCBL1), Villeurbanne (FR); and UNIVERSITÉ DE BRETAGNE OCCIDENTALE, Brest (FR)
Appl. No. 17/042,408
Filed by CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE, Paris (FR); ÉCOLE NORMALE SUPÉRIEURE DE LYON, Lyons (FR); UNIVERSITÉ CLAUDE BERNARD LYON 1 (UCBL1), Villeurbanne (FR); and UNIVERSITÉ DE BRETAGNE OCCIDENTALE, Brest (FR)
PCT Filed Mar. 29, 2019, PCT No. PCT/EP2019/058066
§ 371(c)(1), (2) Date Sep. 28, 2020,
PCT Pub. No. WO2019/185901, PCT Pub. Date Oct. 3, 2019.
Claims priority of application No. 18305380 (EP), filed on Mar. 30, 2018.
Prior Publication US 2021/0017180 A1, Jan. 21, 2021
Int. Cl. C07D 471/08 (2006.01); A61K 49/00 (2006.01)
CPC C07D 471/08 (2013.01) [A61K 49/0021 (2013.01)] 17 Claims
 
1. A compound of Formula (A):

OG Complex Work Unit Chemistry
or a salt thereof;
wherein
Y1, Y2 and Y3 each independently represents —COOH or a picolinate of Formula (i):

OG Complex Work Unit Chemistry
wherein each R1 independently represents
a chromophore group of Formula (ii):

OG Complex Work Unit Chemistry
wherein
m is an integer ranging from 0 to 2;
each R21a independently represents —O-polyether, —S-polyether, —N(polyether)R, or —O-L41-polyether;
 wherein
 R represents hydrogen, alkyl, or polyether;
 L41 represents alkyl, said alkyl optionally additionally comprising a coupling product through which R21a is bound to L41; and
each R21b represents independently alkyl;
or a chromophore group of Formula (iii):

OG Complex Work Unit Chemistry
wherein
n is an integer ranging from 0 to 2;
each R22a independently represents —O-polyether, —S-polyether, —N(polyether)R, or —O-L42-polyether;
 wherein
 R represents hydrogen, alkyl, or polyether;
 L42 represents alkyl, said alkyl optionally additionally comprising a coupling product through which R22a is bound to L42; and
each R22b represents independently alkyl;
provided that at least two among Y1, Y2 and Y3 represents a picolinate of Formula (i);
L1, L2 and L3 each independently represents
a single bond; or
a linker selected from alkyl, aryl, arylalkyl, alkylaryl, heteroalkyl, heteroaryl, heteroarylalkyl, alkylheteroaryl, alkenyl, and alkynyl; said linker optionally additionally comprising a coupling product through which X1, X2 and X3 are bounded to L1, L2 and L3 respectively;
X1, X2 and X3 each independently represents:
a hydrogen atom;
a coupling function selected from amine; isothiocyanate; isocyanate; activated ester; carboxylic acid; activated carboxylic acid; alcohol; alkene; 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 bio-vectorizing group selected from antibody; hapten; peptide; protein; polysaccharide; fatty acid; liposome; lipid; polyamine; nanoparticle; polymeric microparticle; macrocyclic chelate; cationic group suitable for cellular internalization; and combinations thereof.