Releasable glp-1 conjugates

A compound of Formula (I)

• or a pharmaceutically acceptable salt thereof, wherein:
• the aliphatic moiety is selected from a polymer, RP, and a group selected from:
• polymer-L-(CH2)m— and polymer-L-(CH2—CH2—O)p—(CH2)m—;
• RP is selected from optionally substituted C1-6 alkyl, optionally substituted C1-3 alkyl-O—(CH2—CH2—O)p—(CH2)m—, and optionally substituted C3-7 cycloalkyl;
• L is a linking group;
• m and p are each independently an integer from 1 to 10;
• D is a residue of a GLP-1 polypeptide or an analog thereof,
• 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, 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):
• 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.