1,2-benzisoxazol-3-yl compounds
This invention relates to novel 1,2-benzisoxazol-3-yl compounds, their derivatives, pharmaceutically acceptable salts, solvates, and hydrates 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 an antagonist of both dopamine and serotonin receptors.
1. A compound of Formula I
or a salt, hydrate, or solvate thereof, wherein:
each of R 1a and R 1b is -CD 3 ; or
R 1a is CD 3 and R 1b is CH 3 ;
R 2 is selected from CH 2 CH 2 CH 2 , CD 2 CD 2 CD 2 , CD 2 CH 2 CH 2 , and CD 2 CH 2 CD 2 ;
a) R 3a is selected from H, and D; and
R 3b is —OH; or
b) R 3a and R 3b are simultaneously F; or
c) R 3a and R 3b are taken together, with the carbon atom to which they are bound, to form a carbonyl group; and
at least one of R 1a , R 1b , R 2 , R 3a , and R 3b comprises a deuterium atom, and wherein each atom designated as deuterium has a minimum isotopic enrichment factor of at least 3000 (45% deuterium incorporation).
2. The compound of claim 1 , wherein R 1a and R 1b are simultaneously CD 3 .
3. The compound of claim 1 , wherein R 3a and R 3b are taken together with the carbon atom to which they are bound to form a carbonyl group.
4. The compound of claim 1 , wherein R 3a and R 3b are simultaneously F.
5. The compound of claim 1 , selected from any one of the compounds set forth in the following table:
Cmpd
R 1a
R 1b
R 2
R 3a
R 3b
101
CD 3
CH 3
CD 2 CH 2 CH 2
H
OH
104
CD 3
CH 3
CD 2 CH 2 CD 2
H
OH
106
CD 3
CD 3
CD 2 CH 2 CH 2
H
OH
107
CD 3
CD 3
CD 2 CH 2 CD 2
H
OH
118
CD 3
CH 3
CD 2 CH 2 CH 2
F
F
120
CD 3
CH 3
CD 2 CH 2 CD 2
F
F
122
CD 3
CD 3
CD 2 CH 2 CD 2
F
F
131
CD 3
CH 3
CH 2 CH 2 CH 2
═O
132
CD 3
CD 3
CH 2 CH 2 CH 2
═O
134
CD 3
CH 3
CD 2 CH 2 CH 2
═O
136
CD 3
CD 3
CD 2 CH 2 CH 2
═O
138
CD 3
CH 3
CD 2 CH 2 CD 2
═O
140
CD 3
CD 3
CD 2 CH 2 CD 2
═O
141
CD 3
CH 3
CD 2 CD 2 CD 2
═O
142
CD 3
CH 3
CD 2 CD 2 CD 2
F
F
143
CD 3
CH 3
CH 2 CH 2 CH 2
F
F
6. The compound of claim 1 , selected from:
7. The compound of claim 1 , wherein each atom not specified as deuterium is present at its natural isotopic abundance.
8. A pyrogen-free composition comprising an effective amount of the compound of claim 1 and an acceptable carrier.
9. The composition of claim 8 , wherein said composition is formulated for pharmaceutical administration and the carrier is a pharmaceutically acceptable carrier.