Chemical Compounds Useful for Inhibiting Nav1.8 Voltage-Gated Sodium Channels and Treating Nav1.8 Mediated Diseases
AssigneeGlaxoSmithKline Intellectual Property Development Limited
InventorsJie GUANG, David Glenn WASHBURN
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Abstract
Compounds of formula (1) are described, wherein each of the variable groups is as defined in the specification. Also described are pharmaceutical compositions containing a compound of formula (1), and uses of the compounds and pharmaceutical compositions for inhibiting Nav1.8 voltage-gated sodium channels and treating Nav1.8 mediated diseases, disorders, and conditions, such as pain and pain-associated diseases, disorders, and conditions and cardiovascular diseases, disorders, and conditions.
Claims28
-41. (canceled)
A compound of formula (I):
- or a pharmaceutically acceptable salt thereof,
- wherein:
- X1 is N or CH;
- R1 is —P(O)(OH)2;
- R2 is hydrogen, -(C1-6)alkyl, —NRaRb, halo, or -(C1-6)haloalkyl;
- each of R3 and R4 is independently hydrogen, halo, cyano, —NRaRb, -(C1-6)alkyl, -(C1-6)haloalkyl, —O-(C1-6)alkyl, or —O-(C1-6)haloalkyl;
- each R6 is independently halo, -(C1-6)alkyl, —O(C1-6)alkyl, or —O(C1-6)haloalkyl;
- R6 is hydrogen or -(C1-6)alkyl;
- R7 is hydrogen, -(C1-6)alkyl, halo, or -(C1-6)haloalkyl;
- each of Ra and Rb is independently hydrogen or -(C1-6)alkyl;
- and
- n is 0, 1, or 2.
A compound selected from the group consisting of:
- (5-(1-(4-Fluoro-2-methylphenyl)-4-oxo-6-(trifluoromethyl)-1,4-dihydroquinazolin-3(2H)-yl)-6-methyl-2-oxopyridin-1(2H)-yl)methyl dihydrogen phosphate;
- (5-(1-(4-fluoro-2-methylphenyl)-4-oxo-7-(trifluoromethyl)-1,4-dihydroquinazolin-3(2H)-yl)-6-methyl-2-oxopyridin-1(2H)-yl)methyl dihydrogen phosphate;
- (5-(6-chloro-1-(4-fluoro-2-methylphenyl)-4-oxo-1,4-dihydroquinazolin-3(2H)-yl)-6-methyl-2-oxopyridin-1(2H)-yl)methyl dihydrogen phosphate;
- and
- (6-methyl-5-(1-(2-methyl-4-(trifluoromethoxy)phenyl)-4-oxo-6-(trifluoromethyl)-1,4-dihydropyrido[2,3-d]pyrimidin-3(2H)-yl)-2-oxopyridin-1(2H)-yl)methyl dihydrogen phosphate,
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.