Oligomer-phenothiazine conjugates
View Patent ↗The invention relates to (among other things) oligomer-phenothiazine conjugates and related compounds. A conjugate of the invention, when administered by any of a number of administration routes, exhibits advantages over un-conjugated phenothiazine compounds.
1. A compound having the formula:
R 1 , R 2 , R 3 , and R 4 , each independently are selected from the group consisting of hydrogen, unsubstituted alkyl, and substituted alkyl; or R 3 and R 4 together with the nitrogen form a heterocycle;
n is an integer equal to or greater than one;
X is a spacer moiety; and
POLY is a water-soluble, non-peptidic oligomer.
2. The compound of claim 1 , wherein the water-soluble, non-peptidic oligomer is a poly(alkylene oxide).
3. The compound of claim 2 , wherein the poly(alkylene oxide) is a poly(ethylene oxide).
4. The compound of claim 1 , wherein water-soluble, non-peptidic oligomer is made of from about 1 to about 30 monomers.
5. The compound of claim 4 , wherein the water-soluble, non-peptidic oligomer is made of from about 1 to about 10 monomers.
6. The compound of claim 2 , wherein the poly(alkylene oxide) includes an alkoxy or hydroxy end-capping moiety.
7. The compound of claim 1 , wherein a single water-soluble, non-peptidic oligomer is attached to the phenothiazine residue.
8. The compound of claim 1 , wherein more than one water-soluble, non-peptidic oligomer is attached to the phenothiazine residue.
9. The compound of claim 1 , wherein the phenothiazine residue is covalently attached via a stable linkage.
10. The compound of claim 1 , wherein the phenothiazine residue is covalently attached via a degradable linkage.
11. The compound of claim 1 , wherein the linkage is an ether linkage.
12. The compound of claim 1 , wherein the linkage is an ester linkage.
13. A composition comprising the compound of claim 1 , and a pharmaceutically acceptable excipient.
14. The compound of claim 1 , wherein POLY is —(CH 2 CH 2 O) n Y,
wherein Y is selected from H and —CH 3 ; and
n is 1 to 30.
15. The compound of claim 1 , wherein X is —O— or a bond.
16. The compound of claim 1 , having the formula:
17. The compound of claim 1 , having the formula: