Oligomer-foscarnet conjugates
View Patent ↗The invention relates to (among other things) oligomer-foscarnet conjugates and related compounds. A conjugate of the invention, when administered by any of a number of administration routes, exhibits advantages over previously administered un-conjugated foscarnet compounds.
1. A compound according to Formula Ib-C:
or a pharmaceutically acceptable salt thereof, wherein:
X is a spacer moiety; and
POLY is a water-soluble, non-peptidic poly(alkylene oxide) oligomer comprising 3 to 30 alkylene oxide monomers selected from ethylene oxide and propylene oxide.
2. The compound of claim 1 , wherein the alkylene oxide is ethylene oxide.
3. The compound of claim 1 , wherein POLY comprises 3 to 10 monomers of alkylene oxide.
4. The compound of claim 1 , wherein POLY has an alkoxy or hydroxy end-capping moiety.
5. The compound of claim 1 , wherein X is a stable linkage.
6. The compound of claim 1 , wherein Formula Ib-C is attached to POLY via an ester linkage.
7. A composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.
8. The composition of claim 7 , wherein the composition is present in a dosage form.
9. A method of treating herpes simplex virus (HSV), cytomegalovirus (CMV), or human immunodeficiency virus (HIV) comprising administering a compound of claim 1 to a patient in need thereof.
10. The compound of claim 1 , wherein:
X is a single bond, —C(O)—, —OC(O)—, —CH 2 OC(O)—, —C(O)OCH 2 —, —OC(O)CH 2 —, —C(S)—, —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, —OCH 2 —, —OCH 2 CH 2 —, —CH 2 OCH 2 —, —OCH 2 CH 2 CH 2 —, —CH 2 OCH 2 CH 2 —, —CH 2 CH 2 OCH 2 —, —OCH 2 CH 2 CH 2 CH 2 —, —CH 2 OCH 2 CH 2 CH 2 —, —CH 2 CH 2 OCH 2 CH 2 —, —CH 2 CH 2 CH 2 OCH 2 —, —C(O)NHCH 2 —, —C(O)NHCH 2 CH 2 —, —CH 2 C(O)NHCH 2 —, —C(O)NHCH 2 CH 2 CH 2 —, —CH 2 C(O)NHCH 2 CH 2 —, —CH 2 CH 2 C(O)NHCH 2 —, —C(O)NHCH 2 CH 2 CH 2 CH 2 —, —CH 2 C(O)NHCH 2 CH 2 CH 2 —, —CH 2 CH 2 C(O)NHCH 2 CH 2 —, —CH 2 CH 2 CH 2 C(O)NHCH 2 —, —CH 2 CH 2 CH 2 C(O)NHCH 2 CH 2 —, —NHC(O)CH 2 —, —CH 2 NHC(O)CH 2 —, —CH 2 CH 2 NHC(O)CH 2 —, —NHC(O)CH 2 CH 2 —, —CH 2 NHC(O)CH 2 CH 2 —, —CH 2 CH 2 NHC(O)CH 2 CH 2 —, —C(O)NHCH 2 —, —C(O)NHCH 2 CH 2 —, —OC(O)NHCH 2 —, —OC(O)NHCH 2 CH 2 —, —NHCH 2 —, —NHCH 2 CH 2 —, —CH 2 NHCH 2 —, —CH 2 CH 2 NHCH 2 —, —C(O)CH 2 —, —C(O)CH 2 CH 2 —, —CH 2 C(O)CH 2 —, —CH 2 CH 2 C(O)CH 2 —, —CH 2 CH 2 C(O)CH 2 CH 2 —, —CH 2 CH 2 C(O)—, —CH 2 CH 2 CH 2 C(O)NHCH 2 CH 2 NHC(O)—, —CH 2 CH 2 CH 2 C(O)NHCH 2 CH 2 NHC(O)CH 2 —, a bivalent cycloalkyl group, acyl, an alkylene bridge containing between 1 and 5 inclusive carbon atoms, or piperidino.
11. The compound of claim 1 , wherein X is a single bond.