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 buprenorphine, naloxone, naltrexone, desvenlafaxine, 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 .
4 . The pharmaceutical composition of claim 3 , wherein said composition is formulated as an oral tablet or extended release oral tablet.
5 . A homo-dimer compound according to claim 1 , wherein the pharmaceutically active agent is buprenorphine and the homo-dimer compound has the Formula:
or a pharmaceutically acceptable salt or solvate thereof.
6 . A homo-dimer compound according to claim 1 , wherein the pharmaceutically active agent is naloxone and the homo-dimer compound has the Formula:
or a pharmaceutically acceptable salt or solvate thereof.
7 . A homo-dimer compound according to claim 1 , wherein the pharmaceutically active agent is naltrexone and the homo-dimer compound has the Formula:
or a pharmaceutically acceptable salt or solvate thereof.
8 . A homo-dimer compound according to claim 1 , wherein the pharmaceutically active agent is des-venlafaxine and the homo-dimer compound has the Formula:
or a pharmaceutically acceptable salt or solvate thereof.
9 . A homo-dimer compound according to claim 1 , wherein the pharmaceutically active agent is albuterol and the homo-dimer compound has the Formula:
or a pharmaceutically acceptable salt or solvate thereof.
10 . (canceled)