US 11,786,599 B2
Releasable conjugates
Marek Kwiatkowski, Uppsala (SE); and Christian Sund, Varby (SE)
Assigned to QuiaPEG Pharmaceuticals AB, Uppsala (SE)
Filed by QuiaPEG Pharmaceuticals AB, Stockholm (SE)
Filed on Mar. 12, 2018, as Appl. No. 15/918,944.
Claims priority of provisional application 62/564,820, filed on Sep. 28, 2017.
Claims priority of provisional application 62/469,989, filed on Mar. 10, 2017.
Prior Publication US 2018/0360974 A1, Dec. 20, 2018
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/56 (2017.01); A61K 47/54 (2017.01); A61K 47/60 (2017.01); A61P 3/04 (2006.01); A61P 3/10 (2006.01); A61K 38/26 (2006.01)
CPC A61K 47/549 (2017.08) [A61K 38/26 (2013.01); A61K 47/60 (2017.08); A61P 3/04 (2018.01); A61P 3/10 (2018.01)] 27 Claims
 
1. A compound of Formula (B) for releasing a biologically active drug:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
the aliphatic moiety is selected from the group consisting of a polymer, polymer-L-(CH2)m—, and polymer-L-(CH2—CH2—O)p—(CH2)m—;
L is a linking group;
m and p are each independently an integer from 1 to 10;
D is a residue of said biologically active drug;
Z1 is selected from O, S, and N(RN);
Z3 is selected from O and N(RN), or Z3 is absent;
A is O or N, wherein when A is O then R3 is absent;
RN is selected from H and optionally substituted C1-6 alkyl;
R3 is selected from H and C1-6 alkyl, or
R3 and R1, together with A and the carbon atom to which R1 is attached, form an optionally substituted 4 to 7 membered aliphatic heterocyclic ring; or
R3 and R2, together with A to which R3 and E are attached, the carbon atom to which R1 is attached, and the carbon atom to which R2 is attached, form an optionally substituted 4 to 8 membered aliphatic heterocyclic ring;
MA is a self-immolative group having any one of formulae (a)-(i):

OG Complex Work Unit Chemistry
wherein x denotes a point of attachment to Z1 and y denotes a point of attachment to Z3;
R1 and R2 are independently selected from the group consisting of hydrogen, optionally substituted C1-6 alkyl, optionally substituted C6-10 aryl and optionally substituted 5- to 14-membered heteroaryl;
or R1 and R2 are joined together with the carbon atoms to which they are attached to form an optionally substituted C3-7 cycloalkyl ring, an optionally substituted 4 to 7 membered aliphatic heterocyclic ring, an optionally substituted C6-10 aryl or an optionally substituted 5- to 14-membered heteroaryl;
or R1 and R2 are joined together to form a ribose ring system;
R7 and R8 are independently selected from H and C1-6 alkyl; and
E is a cleavable moiety,
wherein said compound of Formula (B) is capable of releasing said biologically active drug upon activation of said self-immolative group.