Deuterated 3-(dihydro-1H-pyrazolo[4,3-D]pyrimidin-5-yl)-4-propoxybenzenesulfonamide derivatives and methods of use
This invention relates to novel 3-(dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-propoxybenzenesulfonamide compounds of Formula I: wherein each Y is independently selected from hydrogen and deuterium and at least one Y is deuterium, as well as to 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 inhibitors of cyclic guanosine 3′,5′-monophosphate specific phosphodiesterase (cGMP-specific PDE), in particular PDE5.
1. A compound of Formula I:
or a salt thereof; wherein:
each of Y 1a , Y 1b , Y 2a , Y 2b , and Y 2c is independently 2 H or 1 H; provided that at least one Y is 2 H, wherein the compound is selected from the group consisting of Compound 100, Compound 103 and Compound 108, as set forth in the table below:
Compound
Y 1a
Y 1b
Y 2a
Y 2b
Y 2c
100
D
D
D
D
D
103
D
D
H
H
H
108
H
H
D
D
D
and wherein a position on the compound designated as having deuterium has a minimum isotopic enrichment factor of at least 3000 (45% deuterium incorporation).
2. The compound of claim 1 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.
3. A pyrogen-free composition comprising:
a compound of claim 1 , or a pharmaceutically acceptable salt thereof; and
an acceptable carrier.
4. The composition of claim 3 , wherein the composition is formulated for pharmaceutical administration and the carrier is a pharmaceutically acceptable carrier.