Substituted triazolo-pyridazine derivatives
This invention relates to novel substituted triazolo-pyridazines, their 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 α1-GABA-A receptor antagonist and/or a α2, α3 and α5 GABA-A receptor agonist.
1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is CH 3 or CD 3 ;
R 2 is —C(CD 3 ) 3 ;
Y 1a and Y 1b are the same and are selected from hydrogen or deuterium;
Y 2 is hydrogen or deuterium; and
the compound has at least 90% deuterium incorporation at each position designated as deuterium.
2. The compound of claim 1 , selected from:
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , wherein the compound has at least 95% deuterium incorporation at each position designated as deuterium.
4. The compound of claim 1 , wherein the compound has at least 97% deuterium incorporation at each position designated as deuterium.
5. The compound of claim 1 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.
6. A pyrogen-free pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.
7. A method of:
a. inhibiting the α-1 subtype of the GABA-A receptor in a cell; or
b. activating one or more of the α2, α3 and α5 subtypes of the GABA-A receptor in a cell,
the method comprising contacting the cell with a compound of claim 1 .
8. A method of treating a patient suffering from a disease or condition selected from neuropathic pain, inflammatory pain, and migraine pain, comprising the step of administering to the patient in need thereof a composition of claim 6 .
9. A method of treating a patient suffering from anxiety or convulsions, the method comprising the step of administering to the patient in need thereof a pharmaceutical composition of claim 6 .