Substituted triazolobenzodiazepines
This invention relates to novel substituted triazolobenzodiazepines of the Formula (I), wherein each of the variables are defined herein and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering I-BET762.
1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein
Y 1a , Y 1b and Y 2 are each independently selected from hydrogen and deuterium;
R 1 and R 2 are each methyl and are independently substituted with 0 to 3 deuterium;
R 3 is ethyl and is substituted with 0 to 5 deuterium; and
if R 1 and R 2 are each CH 3 , R 3 is CH 2 CH 3 , and Y 2 is hydrogen, then at least one of Y 1a and Y 1b is deuterium.
2. The compound of claim 1 , wherein Y 1a and Y 1b are the same.
3. The compound of claim 2 , wherein Y 1a and Y 1b are hydrogen.
4. The compound of claim 2 , wherein Y 1a and Y 1b are deuterium.
5. The compound of claim 1 , wherein R 1 and R 2 are each independently selected from CH 3 and CD 3 .
6. The compound of claim 1 , wherein R 3 is selected from CH 2 CH 3 , CH 2 CD 3 , CD 2 CH 3 , and CD 2 CD 3 .
7. The compound of claim 6 , wherein R 3 is selected from CH 2 CH 3 and CD 2 CD 3 .
8. The compound of claim 3 , selected from any one of the compounds set forth in the table below:
Compound
Y 2
R 1
R 2
R 3
101
H
—CH 3
—CH 3
—CD 2 CD 3
102
H
—CH 3
—CH 3
—CD 2 CH 3
103
H
—CH 3
—CH 3
—CH 2 CD 3
104
H
—CD 3
—CH 3
—CH 2 CH 3
105
H
—CH 3
—CD 3
—CH 2 CH 3
106
D
—CH 3
—CH 3
—CH 2 CH 3
107
D
—CD 3
—CH 3
—CH 2 CH 3
108
D
—CH 3
—CD 3
—CH 2 CH 3
109
D
—CH 3
—CH 3
—CD 2 CD 3
110
D
—CH 3
—CH 3
—CD 2 CH 3
111
D
—CH 3
—CH 3
—CH 2 CD 3
112
H
—CD 3
—CD 3
—CH 2 CH 3
113
H
—CD 3
—CH 3
—CD 2 CD 3
114
H
—CD 3
—CH 3
—CD 2 CH 3
115
H
—CD 3
—CH 3
—CH 2 CD 3
116
H
—CH 3
—CD 3
—CD 2 CD 3
117
H
—CH 3
—CD 3
—CD 2 CH 3
118
H
—CH 3
—CD 3
—CH 2 CD 3
119
D
—CD 3
—CD 3
—CH 2 CH 3
120
D
—CD 3
—CH 3
—CD 2 CD 3
121
D
—CD 3
—CH 3
—CD 2 CH 3
122
D
—CD 3
—CH 3
—CH 2 CD 3
123
D
—CH 3
—CD 3
—CD 2 CD 3
124
D
—CH 3
—CD 3
—CD 2 CH 3
125
D
—CH 3
—CD 3
—CH 2 CD 3
126
H
—CD 3
—CD 3
—CD 2 CD 3
127
H
—CD 3
—CD 3
—CD 2 CH 3
128
H
—CD 3
—CD 3
—CH 2 CD 3
129
D
—CD 3
—CD 3
—CD 2 CD 3
130
D
—CD 3
—CD 3
—CD 2 CH 3
131
D
—CD 3
—CD 3
—CH 2 CD 3
or a pharmaceutically acceptable salt thereof.
9. The compound of claim 4 , selected from any one of the compounds set forth in the table below:
Compound
Y 2
R 1
R 2
R 3
200
H
—CH 3
—CH 3
—CH 2 CH 3
201
H
—CH 3
—CH 3
—CD 2 CD 3
202
H
—CH 3
—CH 3
—CD 2 CH 3
203
H
—CH 3
—CH 3
—CH 2 CD 3
204
H
—CD 3
—CH 3
—CH 2 CH 3
205
H
—CH 3
—CD 3
—CH 2 CH 3
206
D
—CH 3
—CH 3
—CH 2 CH 3
207
D
—CD 3
—CH 3
—CH 2 CH 3
208
D
—CH 3
—CD 3
—CH 2 CH 3
209
D
—CH 3
—CH 3
—CD 2 CD 3
210
D
—CH 3
—CH 3
—CD 2 CH 3
211
D
—CH 3
—CH 3
—CH 2 CD 3
212
H
—CD 3
—CD 3
—CH 2 CH 3
213
H
—CD 3
—CH 3
—CD 2 CD 3
214
H
—CD 3
—CH 3
—CD 2 CH 3
215
H
—CD 3
—CH 3
—CH 2 CD 3
216
H
—CH 3
—CD 3
—CD 2 CD 3
217
H
—CH 3
—CD 3
—CD 2 CH 3
218
H
—CH 3
—CD 3
—CH 2 CD 3
219
D
—CD 3
—CD 3
—CH 2 CH 3
220
D
—CD 3
—CH 3
—CD 2 CD 3
221
D
—CD 3
—CH 3
—CD 2 CH 3
222
D
—CD 3
—CH 3
—CH 2 CD 3
223
D
—CH 3
—CD 3
—CD 2 CD 3
224
D
—CH 3
—CD 3
—CD 2 CH 3
225
D
—CH 3
—CD 3
—CH 2 CD 3
226
H
—CD 3
—CD 3
—CD 2 CD 3
227
H
—CD 3
—CD 3
—CD 2 CH 3
228
H
—CD 3
—CD 3
—CH 2 CD 3
229
D
—CD 3
—CD 3
—CD 2 CD 3
230
D
—CD 3
—CD 3
—CD 2 CH 3
231
D
—CD 3
—CD 3
—CH 2 CD 3
or a pharmaceutically acceptable salt thereof.
10. The compound of claim 1 , wherein the compound has an isotopic enrichment factor for each designated deuterium atom of at least 6000 (90% deuterium incorporation).
11. The compound of claim 10 , wherein the compound has an isotopic enrichment factor for each designated deuterium atom of at least 6333.3 (95% deuterium incorporation).
12. A pharmaceutical composition comprising an effective amount of the compound of claim 1 ; and a pharmaceutically acceptable carrier.