Patent ID: 11896671
Assignee: ASCENDIS PHARMA A/S
Field: Pharmaceuticals (Chemistry)
Classification: CPC A  C | IPC A

Claim 17:
18. A method of synthesizing a carrier-linked prodrug, the method comprising the step of reacting a compound of formula (I)

D-(L1-L2-A)a  (I),

wherein
-D is a drug moiety;
each -L1- is independently a reversible prodrug linker, which is covalently conjugated to -D through a reversible linkage that is cleavable in the absence of enzymes in aqueous buffer at pH 7.4 and 37° C.;
each -L2- is independently a chemical bond or a spacer;
each -A is —X0 or —Y0;
a is selected from the group consisting of 1, 2, 3, 4, 5, 6, 7 and 8;
—X0 is a substituted acyl borate; and
—Y0 is a substituted hydroxylamine;, under aqueous conditions with a compound of formula (II)

Z-(L2′-B0)b  (II),

wherein
—Z is a carrier comprising a C8-24 alkyl moiety or a polymeric moiety;
-L2′- is a chemical bond or a spacer;
—B0 is —Y0;
b is an integer of at least 1; and
—Y0 is a substituted hydroxylamine;, with -A being —X0 and —B0 being —Y0, and forming an amide bond between moiety -A and a moiety —B0.