Kappa opioid receptor selective compounds, compositions, and uses thereof
The present invention provides, inter alia, compounds of formula (I): (structurally represented). Also provided are pharmaceutical compositions containing such compounds and methods for treating or ameliorating the effects of a medical condition in a subject using such compounds or pharmaceutical compositions.
1. A compound of formula I:
wherein
X 1 is N;
n is an integer between 1 and 10;
HET is a heteroaromatic ring; and
R is a —C 1-4 alkylhalo; or
crystalline forms, hydrates, or salts thereof.
2. A compound of formula II:
wherein
X 1 and X 3 are N;
X 2 is selected from the group consisting of N, O, and S;
n is an integer between 1 and 10; and
R is a —C 1-4 alkylhalo; or
crystalline forms, hydrates, or salts thereof.
3. A compound of formula V:
wherein
n is selected from an integer between 1 and 10; and
R is a —C 1-4 alkylhalo; or
crystalline forms, hydrates, or salts thereof.
4. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.
5. A method for treating or ameliorating the effects of a condition in a subject in need thereof comprising administering to the subject an effective amount of a compound according to claim 1 , wherein the condition is selected from the group consisting of pain, coughing, depression, and itching.
6. The method according to claim 5 , wherein the subject is a human.
7. A method for treating or ameliorating the effects of a condition in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition according to claim 4 , wherein the condition is selected from the group consisting of pain, coughing, depression, and itching.
8. The method according to claim 7 , wherein the subject is a human.
9. A method for treating pain in a subject comprising administering to the subject an effective amount of a non-addictive pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of formula I:
wherein
X 1 is N;
n is an integer between 1 and 10;
HET is a heteroaromatic ring; and
R is a —C 1-4 alkylhalo; or
crystalline forms, hydrates, or salts thereof;
further wherein the compound is biased toward G protein activation over arrestin.
10. A compound of the structure:
or crystalline forms, hydrates, or salts thereof.
11. A pharmaceutical composition comprising the compound according to claim 10 and a pharmaceutically acceptable carrier.