Chemically modified small molecules
View Patent ↗The invention provides small molecule drugs that are chemically modified by covalent attachment of a water-soluble oligomer obtained from a monodisperse or bimodal water-soluble oligomer composition. A conjugate of the invention, when administered by any of a number of administration routes, exhibits a reduced biological membrane crossing rate as compared to the biological membrane crossing rate of the small molecule drug not attached to the water-soluble oligomer.
1. A compound selected from the group consisting of:
6-CH 3 -(OCH 2 CH 2 ) 5 -O-naloxol;
6-CH 3 -(OCH 2 CH 2 ) 6 -O-naloxol;
6-CH 3 -(OCH 2 CH 2 ) 8 -O-naloxol; and
6-CH 3 -(OCH 2 CH 2 ) 9 -O-naloxol;
or a pharmaceutically acceptable salt thereof, wherein the compound is an α-6 isomer, a β-6 isomer or a mixture of α-6 and β-6 isomers.
2. The compound of claim 1 , wherein the compound is selected from the group consisting of
α,β-6-CH 3 -(OCH 2 CH 2 ) 5 -O-naloxol;
α,β-6-CH 3 -(OCH 2 CH 2 ) 6 -O-naloxol;
α,β-6-CH 3 -(OCH 2 CH 2 ) 8 -O-naloxol; and
α,β-6-CH 3 -(OCH 2 CH 2 ) 9 -O-naloxol;
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 2 , wherein the compound is α,β-6-CH 3 -(OCH 2 CH 2 ) 5 -O-naloxol or a pharmaceutically acceptable salt thereof.
4. The compound of claim 2 , wherein the compound is α,β-6-CH 3 -(OCH 2 CH 2 ) 6 -O-naloxol or a pharmaceutically acceptable salt thereof.
5. The compound of claim 2 , wherein the compound is α,β-6-CH 3 -(OCH 2 CH 2 ) 8 -O-naloxol or a pharmaceutically acceptable salt thereof.
6. The compound of claim 2 , wherein the compound is α,β-6-CH 3 -(OCH 2 CH 2 ) 9 -O-naloxol or a pharmaceutically acceptable salt thereof.
7. The compound of claim 1 , wherein the compound is selected from the group consisting of
α-6-CH 3 -(OCH 2 CH 2 ) 5 -O-naloxol;
α-6-CH 3 -(OCH 2 CH 2 ) 6 -O-naloxol;
α-6-CH 3 -(OCH 2 CH 2 ) 8 -O-naloxol; and
α-6-CH 3 -(OCH 2 CH 2 ) 9 -O-naloxol;
or a pharmaceutically acceptable salt thereof.
8. The compound of claim 7 , wherein the compound is α-6-CH 3 -(OCH 2 CH 2 ) 5 -O-naloxol or a pharmaceutically acceptable salt thereof.
9. The compound of claim 7 , wherein the compound is α-6-CH 3 -(OCH 2 CH 2 ) 6 -O-naloxol or a pharmaceutically acceptable salt thereof.
10. The compound of claim 7 , wherein the compound is α-6-CH 3 -(OCH 2 CH 2 ) 8 -O-naloxol or a pharmaceutically acceptable salt thereof.
11. The compound of claim 7 , wherein the compound is α-6-CH 3 -(OCH 2 CH 2 ) 9 -O-naloxol or a pharmaceutically acceptable salt thereof.
12. The compound of claim 1 , wherein the compound is selected from the group consisting of
β-6-CH 3 -(OCH 2 CH 2 ) 5 -O-naloxol;
β-6-CH 3 -(OCH 2 CH 2 ) 6 -O-naloxol;
β-6-CH 3 -(OCH 2 CH 2 ) 8 -O-naloxol; and
β-6-CH 3 -(OCH 2 CH 2 ) 9 -O-naloxol;
or a pharmaceutically acceptable salt thereof.
13. The compound of claim 12 , wherein the compound is β-6-CH 3 -(OCH 2 CH 2 ) 5 -O-naloxol or a pharmaceutically acceptable salt thereof.
14. The compound of claim 12 , wherein the compound is β-6-CH 3 -(OCH 2 CH 2 ) 6 -O-naloxol or a pharmaceutically acceptable salt thereof.
15. The compound of claim 12 , wherein the compound is β-6-CH 3 -(OCH 2 CH 2 ) 8 -O-naloxol or a pharmaceutically acceptable salt thereof.
16. The compound of claim 12 , wherein the compound is β-6-CH 3 -(OCH 2 CH 2 ) 9 -O-naloxol or a pharmaceutically acceptable salt thereof.
17. A pharmaceutical composition comprising a compound of any one of claims 1 - 16 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.