Azetidine-substituted pyridine and pyrazine compounds as inhibitors of cannabinoid receptor 2
The invention relates to a compound of formula (I) wherein A 1 and R 1 -R 4 are as defined in the description and in the claims. The compound of formula (I) can be used as a medicament.
1. A compound of formula (I)
wherein
A is —CH— or nitrogen;
R 1 is haloalkoxyazetidinyl, halosulfonylazetidinyl, 3-fluoro-3,3-dideuteriopropyloxyazetidinyl, 2-fluoro-2,2-dideuterio-ethyloxyazetidinyl, fluorodideuteriomethoxyazetidinyl, 2-fluoro-2,2-dideuterioethylazetidinyl or fluorodideuteriomethylazetidinyl;
R 2 and R 3 are both alkyl at the same time; or
R 2 and R 3 , together with the carbon atom to which they are attached, form oxetanyl; and
R 4 is alkoxycarbonyl or aminocarbonylalkyl;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein A is —CH—.
3. The compound of claim 1 , wherein R 1 is haloalkoxyazetidinyl.
4. The compound of claim 3 , wherein R 1 is fluoroethoxyazetidinyl.
5. The compound of claim 1 , wherein R 2 and R 3 are both ethyl at the same time.
6. The compound of claim 1 , wherein R 4 is alkoxycarbonyl.
7. The compound of claim 6 , wherein R 4 is ethoxycarbonyl.
8. The compound of claim 1 selected from the group consisting of:
ethyl 2-({6-(cyclopropylmethoxy)-5-[3-(3-fluoropropoxy)azetidin-1-yl]pyridine-2-carbonyl}amino)-2-ethylbutanoate;
ethyl 2-({6-(cyclopropylmethoxy)-5-[3-(2-fluoroethoxy)azetidin-1-yl]pyridine-2-carbonyl}amino)-2-ethylbutanoate;
ethyl 2-({6-(cyclopropylmethoxy)-5-[3-(fluoromethoxy)azetidin-1-yl]pyridine-2-carbonyl}amino)-2-ethylbutanoate;
N-[3-(2-amino-2-oxoethyl)oxetan-3-yl]-6-(cyclopropylmethoxy)-5-[3-(2-fluoroethoxy)azetidin-1-yl]pyridine-2-carboxamide;
ethyl 2-({6-(cyclopropylmethoxy)-5-[3-(fluorosulfonyl)azetidin-1-yl]pyridine-2-carbonyl}amino)-2-ethylbutanoate;
ethyl 2-({6-(cyclopropylmethoxy)-5-[3-(fluorosulfonyl)azetidin-1-yl]pyridine-2-carbonyl}amino)-2-ethylbutanoate;
ethyl 2-{[6-(cyclopropylmethoxy)-5-(3-{[3-fluoro(3,3-dideuterio)propyl]oxy}azetidin-1-yl)pyridine-2-carbonyl]amino}-2-ethylbutanoate;
ethyl 2-{[6-(cyclopropylmethoxy)-5-(3-{[2-fluoro(2,2-dideuterio)ethyl]oxy}azetidin-1-yl)pyridine-2-carbonyl]amino}-2-ethylbutanoate;
ethyl 2-{[6-(cyclopropylmethoxy)-5-(3-{[fluoro(dideuterio)methyl]oxy}azetidin-1-yl)pyridine-2-carbonyl]amino}-2-ethylbutanoate;
N-[3-(2-amino-2-oxoethyl)oxetan-3-yl]-6-(cyclopropylmethoxy)-5-(3-{[2-fluoro(2,2-dideuterio)ethyl]oxy}azetidin-1-yl)pyridine-2-carboxamide;
ethyl 2-{[6-(cyclopropylmethoxy)-5-{3-[2-fluoro(2,2-dideuterio)ethyl]azetidin-1-yl}pyridine-2-carbonyl]amino}-2-ethylbutanoate;
ethyl 2-{[6-(cyclopropylmethoxy)-5-{3-[fluoro(dideuterio)methyl]azetidin-1-yl}pyridine-2-carbonyl]amino}-2-ethylbutanoate; and
ethyl 2-({6-(cyclopropylmethoxy)-5-[3-(2-fluoroethyl)azetidin-1-yl]pyridine-2-carbonyl}amino)-2-ethylbutanoate;
or a pharmaceutically acceptable salt thereof.
9. The compound of claim 1 , wherein the compound is
ethyl 2-({6-(cyclopropylmethoxy)-5-[3-(2-fluoroethoxy)azetidin-1-yl]pyridine-2-carbonyl}amino)-2-ethylbutanoate
or a pharmaceutically acceptable salt thereof.
10. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.