Analgesic conjugates
The invention provides analgesic conjugates having a mu opioid receptor agonist linked to a mGluR 5 antagonist, and to methods for producing analgesia using such compounds.
1. A conjugate having the formula:
R 1 —X—R 2
wherein:
R 1 is a mu opioid receptor agonist having the following formula:
R 2 is a mGluR 5 antagonist having the following formula:
X is a linker selected from the group consisting of —CO—CH 2 OCH 2 CO—NH—(CH 2 ) n2 NH—CO—CH 2 OCH 2 CO—, —CO—CH 2 O(CH 2 CH 2 O) n3 CH 2 CO—, —(CO—CH 2 NH) x2 —CO—(CH 2 ) n4 —CO—(NH—CH 2 CO) x2 —, —CO—(CH 2 ) n3 CO—,
n1 is any integer from 1-10;
n2 is any integer from 1-8;
n3 is any integer from 1-20;
n4 is any integer from 12-22; and
x2 is any integer from 1-2;
or a salt thereof.
2. The conjugate of claim 1 wherein the Mu opioid receptor agonist has the following formula:
3. The conjugate of claim 1 wherein X has the following structure:
wherein n 1 is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
4. The conjugate of claim 3 wherein n 1 is 3, 4, 5, 6, or 7.
5. The conjugate of claim 3 wherein n 1 is 5.
6. A pharmaceutical composition comprising a conjugate as described in claim 1 and a pharmaceutically acceptable carrier.
7. A method for treating pain in an animal comprising administering a conjugate as described in claim 1 , or a pharmaceutically acceptable salt thereof, to the animal.
8. A conjugate which has the formula:
wherein n 1 is 2, 3, 5, or 7; or a salt thereof.
9. The compound 4c:
or a salt thereof.