Deuterated ibrutinib
View Patent ↗The present invention in one embodiment provides a compound of Formula (I); or a pharmaceutically acceptable salt thereof, wherein the variables shown in Formula (I) are as defined in the specification.
1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
each Y 1 , each Y 2 , each Y 3 , each Y 4 and Y 5 is deuterium; and
Y 6 , each Y 7 , each Y 8 , each Y 9 , each Y 10 ,Y 11 ,Y 12 , Y 13 and Y 14 is independently selected from hydrogen and deuterium, wherein any atom not designated as deuterium is present at its natural isotopic abundance.
2. The compound of claim 1 , wherein Y 12 ,Y 13 , and Y 14 are each hydrogen.
3. The compound of claim 1 , wherein Y 12 ,Y 13 , and Y 14 are each deuterium.
4. The compound of claim 1 , wherein each Y 7 is hydrogen and each Y 8 is hydrogen.
5. The compound of claim 1 , wherein each Y 7 is deuterium and each Y 8 is deuterium.
6. The compound of claim 1 , wherein the compound is selected from any one of the compounds (Cmpd) set forth in the table below:
Y 9 =
Y 12 =
Cmpd
Y 7 =
Y 10 =
Y 13 =
#
Y 1
Y 2
Y 3
Y 4
Y 5
Y 6
Y 8
Y 11
Y 14
107
D
D
D
D
D
H
H
H
H
109
D
D
D
D
D
D
H
H
H
118
D
D
D
D
D
H
H
H
D
120
D
D
D
D
D
D
H
H
D
127
D
D
D
D
D
H
D
D
H
128
D
D
D
D
D
H
D
D
D
129
D
D
D
D
D
D
D
D
H
130
D
D
D
D
D
D
D
D
D
or a pharmaceutically acceptable salt thereof.
7. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.
8. A method of inhibiting BTK in a cell, comprising contacting the cell with a compound of claim 1 .
9. A method of treating a disease selected from the group consisting of chronic lymphocytic leukemia, mantle cell lymphoma, and multiple myeloma, comprising administering to a subject in need of such treatment a compound of claim 1 .