Pharmaceutically active dimers linked through phenolic hydroxyl groups
Pharmaceutically active homo-dimers of opioid and other pharmaceutically active agents characterized by a single phenolic hydroxyl group wherein the respective monomers are ether-linked through such groups by an ethylene residue. The dimers share the receptor pharmacology of the corresponding monomer, in particular cases are non-absorbed, and the ether link of the dimers is particularly resistant to metabolism when administered to a subject, all conferring divers advantages relative to the corresponding monomers. Exemplary of the dimers are those of buprenorphine, naloxone, naltrexone, des-venlafaxine, albuterol and acetaminophen.
1. A homo-dimer compound of a pharmaceutically active agent selected from the group consisting of naloxone, naltrexone, des-venlafaxine and albuterol wherein two such agents are covalently ether-linked through phenolic hydroxyl groups of the agents by an ethylene residue, or a pharmaceutically acceptable salt or solvate thereof.
2. A homo-dimer compound according to claim 1 , wherein the compound is in the form of a pharmaceutically acceptable salt.
3. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a dimer compound according to claim 1 or 2 .
4. The pharmaceutical composition of claim 3 , wherein said composition is formulated as an oral tablet or capsule or extended release oral tablet or capsule.
5. A naloxone dimer compound having the Formula:
or a pharmaceutically acceptable salt or solvate thereof.
6. A naltrexone dimer compound having the Formula:
or a pharmaceutically acceptable salt or solvate thereof.
7. A des-venlafaxine dimer compound having the Formula:
or a pharmaceutically acceptable salt or solvate thereof.
8. An albuterol dimer compound having the Formula:
or a pharmaceutically acceptable salt or solvate thereof.
9. A homo-dimer compound of claim 2 , wherein the pharmaceutically acceptable salt is a citric acid salt.
10. A dimer compound of any one of claim 5 , 6 7 or 8 , in a citric acid salt form.