Polymeric hGH prodrugs

A polymeric human growth hormone (hGH) prodrug or a pharmaceutically acceptable salt thereof of formula (Ia) or (Ib):

• wherein:
• -D is a hGH moiety connected to the rest of the molecule through an amine functional group;
• n is 0, 1, 2, 3, or 4;
• —X— is a chemical bond or a spacer;
• =Y1, is selected from the group consisting of =0 and =S;
• —Y2— is selected from the group consisting of —0— and —S—;
• —Y3— and —Y5— are independently of each other selected from the group
• consisting of —0— and —S—;
• —Y4— is selected from the group consisting of —0—, —NR5— and —C(R6R6a)—;
• —R1 comprises a moiety of formula-(IIc):
• wherein:
• p1, p2, p3, and p4 are independently an integer ranging from 180 to 240;
• —R2, —R3, —R5, —R6, and —R6a are independently of each other selected from the group consisting of -H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl and 3,3-dimethylpropyl;
• —R4 is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tent-butyl, n-pentyl, 2-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl and 3,3-dimethylpropyl;
• —W— is selected from the group consisting of C1-20 alkyl optionally interrupted by one or more groups selected from the group consisting of C3-10 cycloalkyl, 8- to 30-membered carbopolycyclyl, 3- to 10-membered heterocyclyl, —C(O)—, —C(O)N(R7)—, —O—, —S—, and —N(R7)—;
• —Nu is a nucleophile selected from the group consisting of —N(R7R7a),
• —Ar— is selected from the group consisting of
• wherein:
• dashed lines indicate attachment to the rest of the prodrug,
• —Z1— is selected from the group consisting of —O—, —S— and —N(R7)—, and
• —Z2— is —N(R7)—;
• and
• —R7, —R7a, and —R7b are independently of each other selected from the group consisting of —H, C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl;
• and
• wherein the prodrug of formula (Ia) and (Ib) is optionally further substituted.