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 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 Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is CH 3 or CD 3 ;
R 2 is —C(CD 3 ) 3 ; and
each of Y 1a , Y 1b , and Y 2 is independently hydrogen or deuterium.
2. 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 comprising 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 ; and
each of Y 1a Y 1b , and Y 2 is independently hydrogen or deuterium;
and an acceptable carrier.
3. The method of claim 2 , wherein Y 1a and Y 1b are the same.
4. The method of claim 3 , wherein the compound of formula I is selected from any one of the following compounds:
or a pharmaceutically acceptable salt thereof.
5. The method of claim 4 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
6. The method of claim 2 , wherein in the compound of formula I any atom not designated as deuterium is present at its natural isotopic abundance.
7. The method of claim 2 , wherein the composition is formulated for pharmaceutical administration, wherein the carrier is a pharmaceutically acceptable carrier.
8. The method of claim 7 , wherein the composition is formulated for oral administration.
9. The method of claim 2 , wherein the disease or condition is inflammatory pain.