US 12,459,928 B2
Therapeutic vectors and prodrugs for treating cancers
Sébastien Papot, Poitiers (FR); Brigitte Renoux, Nouaille Maupertuis (FR); and Rémi Chatre, Poitiers (FR)
Assigned to SEEKYO, Futuroscope (FR); and CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE, Paris (FR)
Appl. No. 17/595,012
Filed by SEEKYO, Futuroscope (FR); and CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE, Paris (FR)
PCT Filed May 6, 2020, PCT No. PCT/EP2020/062617
§ 371(c)(1), (2) Date Nov. 5, 2021,
PCT Pub. No. WO2020/225323, PCT Pub. Date Nov. 12, 2020.
Claims priority of application No. 19305574 (EP), filed on May 6, 2019.
Prior Publication US 2022/0227741 A1, Jul. 21, 2022
Int. Cl. A61K 47/64 (2017.01); A61K 47/54 (2017.01); A61K 47/55 (2017.01); C07D 405/14 (2006.01)
CPC C07D 405/14 (2013.01) [A61K 47/549 (2017.08); A61K 47/55 (2017.08); A61K 47/643 (2017.08)] 16 Claims
 
1. A compound having the following formula (I):

OG Complex Work Unit Chemistry
wherein:
Ra represents H or a (C1-C12)alkyl group, optionally interrupted with one or several oxygen atoms;
L represents a group having the following formula (II):

OG Complex Work Unit Chemistry
wherein:
A is an anticancer agent;
Y is an electron-withdrawing group;
X is —O—;
G is a glucuronyl radical or a derivative thereof;
L1 represents a linker represented by the following formula (III):
-A1-A2-A3-A4-A5-A6-A7-  (III)
wherein:
A1 is an (C1-C6)alkylene radical;
A2 is a triazole radical;
A3 is an (C1-C6)alkylene radical;
A4 is chosen from the group consisting of: —C(═O)—NRb—, —C(═S)—NRb—, —NRb—C(═O)—, —NRb—C(═S)—, and NRb, Rb representing H or a (C1-C12)alkyl group;
A5 is an (C1-C32)alkylene radical interrupted by at least on oxygen atom;
A6 is a triazole radical;
A7 is an (C1-C6)alkylene radical;
L′ represents a group having the following formula (IV):
-A8-A9-L″  (IV)
wherein:
A8 is an (C1-C6)alkylene radical interrupted by at least one oxygen atom;
A9 is chosen from the group consisting of: —NRc—, —O—, and —S—, Rc representing H or a (C1-C12)alkyl group; and
L″ is a maleimidocaproyl group or a radical having one of the following formulae:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, or a racemate, diastereomer or enantiomer thereof.