Deuterated 2-amino-3-hydroxypropanoic acid derivatives
This invention relates to novel 2-amino-3-hydroxypropanoic acid derivatives 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 an NMDA glycine-site antagonist.
1. A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
Y 1 is CD 3 ;
Y 2 is CD 3 ;
each Z variable is independently selected from hydrogen and deuterium;
each R variable is independently selected from hydrogen and deuterium; and
any atom not designated as deuterium is present at its natural isotopic abundance; and wherein for each site designated as deuterium, deuterium incorporation is at least 90%.
2. The compound of claim 1 , wherein for each site designated as deuterium, deuterium incorporation is at least 95%.
3. The compound of claim 1 , wherein each Z is hydrogen.
4. The compound of claim 1 , wherein each Z is deuterium.
5. The compound of claim 1 , wherein the compound is selected from the group consisting of the following:
or a pharmaceutically acceptable salt of any of the foregoing.
6. The compound of claim 5 , wherein the compound is an (R) enantiomer, or a pharmaceutically acceptable salt thereof, which is substantially free of the corresponding (S) enantiomer.
7. A composition comprising a compound of claim 1 , wherein any atom not designated as deuterium is present at its natural isotopic abundance; and wherein for each site designated as deuterium, deuterium incorporation is at least 90%, and a pharmaceutically acceptable carrier.
8. The composition of claim 7 for use in treating a disease or disorder associated with aberrant NMDA receptor function.
9. The composition of claim 7 for use in treating epilepsy, diabetic neuropathic pain, fibromyalgia, osteoarthritis, or migraine.
10. The compound of claim 5 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof.
11. The compound of claim 10 , wherein the compound is an (R) enantiomer, or a pharmaceutically acceptable salt thereof, which is substantially free of the corresponding (S) enantiomer.
12. A composition comprising a compound of claim 11 , wherein any atom not designated as deuterium is present at its natural isotopic abundance; and wherein for each site designated as deuterium, deuterium incorporation is at least 90% and a pharmaceutically acceptable carrier.
13. The composition of claim 12 for use in treating a disease or disorder associated with aberrant NMDA receptor function.
14. The composition of claim 12 for use in treating epilepsy, diabetic neuropathic pain, fibromyalgia, osteoarthritis, or migraine.