KAPPA OPIOID RECEPTOR ANTAGONISTS AND PRODUCTS AND METHODS RELATED THERETO
Compounds are provided that antagonize the kappa-opioid receptor (KOR) and products containing such compounds, as well as to methods of their use and synthesis. Such compounds have the structure of Formula (I), or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope or salt thereof: wherein X, Y, R 1 , R 2 , R 4 , R 5 R 6 , R 7 , R 8 and R 11 are as defined herein.
1 - 148 . (canceled)
149 . A method of treating a bipolar disorder, comprising administering to a subject in need thereof an effective amount of a compound having the structure of Formula (XI):
or a pharmaceutically acceptable stereoisomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein
R 1 is H, F, or lower alkyl;
R 2 is H or lower alkyl;
R 4 is lower alkyl;
R 8 is halo or cyano;
R 5 and R 7 are both H; and
R 6 is lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, cycloalkoxy, lower alkynyl, cycloalkyl, halo, or cyano.
150 . The method of claim 149 , wherein R 1 is H.
151 . The method of claim 149 , wherein R 2 is H.
152 . The method of claim 151 , wherein R 4 is methyl.
153 . The method of claim 149 , wherein R 6 is lower alkyl.
154 . The method of claim 153 , wherein R 6 is methyl or ethyl.
155 . The method of claim 149 , wherein R 8 is halo.
156 . The method of claim 156 , wherein R 8 is fluoro.
157 . The method of claim 149 , wherein the compound having the structure of Formula (XI) is a compound having one of the following structures, or a pharmaceutically acceptable stereoisomer, racemate, hydrate, solvate, isotope, or salt thereof:
158 . The method of claim 149 , wherein the compound is administered orally.
159 . The method of claim 158 , wherein the compound for oral administration is a tablet, capsule, troche, lozenge, syrup, or emulsion.
160 . The method of claim 159 , wherein the compound for oral administration is a tablet or capsule.
161 . The method of claim 149 , wherein the compound is administered once a day.
162 . The method of claim 149 , wherein the compound is administered two or three times a day.
163 . The method of claim 149 , wherein the bipolar disorder is bipolar I.
164 . The method of claim 149 , wherein the bipolar disorder is bipolar II.
165 . The method of claim 149 , wherein the bipolar disorder is cyclothymic disorder.
166 . A method of treating a bipolar disorder, comprising administering to a subject in need thereof an effective amount of:
167 . The method of claim 166 , wherein the compound is administered orally.
168 . The method of claim 167 , wherein the compound for oral administration is a tablet, capsule, troche, lozenge, syrup, or emulsion.
169 . The method of claim 166 , wherein the compound for oral administration is a tablet or capsule.
170 . The method of claim 166 , wherein the compound is administered once a day.
171 . The method of claim 166 , wherein the compound is administered two or three times a day.
172 . The method of claim 166 , wherein the bipolar disorder is bipolar I.
173 . The method of claim 166 , wherein the bipolar disorder is bipolar II.
174 . The method of claim 166 , wherein the bipolar disorder is cyclothymic disorder.