Compounds as cannabinoid receptor ligands

1. A compound of formula (I),

or a pharmaceutically acceptable salt, solvate, or salt of a solvate thereof, wherein

R x is a phenyl or heteroaryl, each of which is substituted with 2 substituents independently selected from the group consisting of halogen, haloalkyl, —OR a , —OC(O)R e , —C(O)R f , —C(O)OR f , —(CR 1a R 1b ) q1 —, —OR a , —(CR 1a R 1b ) q1 —OC(O)R e , —(CR 1a R 1b ) q1 —C(O)C)R f , and —(CR 1a R 1b ) q1 —C(O)OR f ;

R a is —(CR 1c R 1d ) q2 —C(O)R b , —(CR 1c R 1d ) q4 —OR b , or —(CR 1c R 1d ) q2 —OC(O)R b ;

R b and R f , at each occurrence, are each independently hydrogen, alkyl, haloalkyl, G b , hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, or —(C 1 -C 6 alkylene)-G a ;

R e , at each occurrence, is independently alkyl, haloalkyl, G, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, or —(C 1 -C 6 alkylene)-G a ;

G a at each occurrence, is independently aryl, heteroaryl, cycloalkyl, cycloalkenyl, or heterocycle, each of which is independently unsubstituted or substituted with 1, 2, 3, or 4 substituents selected from the group consisting of C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, halogen, C 1 -C 4 haloalkyl, G b , oxo, —CN, NO 2 , —OR g , —OC(O)R g , —OC(O)N(R g ) 2 , —S(O) 2 R b , —S(O) 2 N(R g ) 2 , —C(O)R g , —C(CO)OR g , —C(O)N(R g ) 2 , —N(R g ) 2 , —N(R g )C(O)R g , —N(R f )S(O) 2 R b , —N(R g )C(O)O(R g ), —N(R g )C(O)N(R g ) 2 , —(CR 1e R 1f ) q3 -G b , —(CR 1e R 1f ) g3 —OR g , —(CR 1e R 1f ) q3 —OC(O)R g , —(CR 1e R f ) g3 —OC(O)N(R g ) 2 , —(CR 1e R 1f ) q3 —S(O) 2 R h , —(CR 1e R 1f ) q3 —S(O) 2 N(R g ) 2 , —(CR 1e R 1f ) q3 —C(O)R g , —(CR 1e R 1f ) q3 —C(O)OR g , —(CR 1e R 1f ) q3 —C(O)N(R g ) 2 —(CR 1e R 1f ) q3 —N(R g ) 2 , —(CR 1e R 1f ) q3 —N(R g )C(O)R g , —CR 1e R 1f ) q3 —N(R g )S(O) 2 R h , —(CR 1e R 1f ) q3 —N(R g )C(O)O(R g ), —(CR 1e R 1f ) q3 N(R g )C(O)N(R g ) 2 , and —(CR 1e R 1f ) q3 —CN;

G b , at each occurrence, is independently aryl, heteroaryl, cycloalkyl, cycloalkenyl, or heterocycle, each of which is independently unsubstituted or substituted with 1, 2, 3, or 4 substituents selected from the group consisting of —C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, halogen, C 1 -C 4 haloalkyl, —CN, NO 2 , —OR j , —OC(O)R j , —OC(O)N(R j ) 2 , —S(O) 2 R k , —S(O) 2 N(R j ) 2 , —C(O)R j , C(O)OR j , —C(O)N(R j ) 2 , —N(R j ) 2 , —N(R j )C(O)R j , N(R j )S(O) 2 R j , N(R j )C(O)O(R j ), —N(R j )C(O)N(R j ) 2 , —(CR 1e R 1f ) q3 —OR j , —(CR 1e R 1f ) q3 —OC(O)R j , —(CR 1e R 1f ) q3 —OC(O)N(R j ) 2 , —(CR 1e R 1f ) q3 , —S(O) 2 R k , —(CR 1e R 1f ) q3 —S(O) 2 N(R j ) 2 , —(CR 1e R 1f ) q3 —C(O)R j , —(CR 1e R 1f ) q3 —C(O)OR j , —(CR 1e R 1f ) q3 —C(O)N(R j ) 2 , —(CR 1e R 1f ) q3 —N(R j ) 2 , —(CR 1e R 1f ) q3 —N(R j )C(O)R j , —(CR 1e R 1f ) q3 —N(R j )S(O) 2 R k , —(CR 1e R 1f ) q3 —N(R j )C(O)O(R j ), —CR 1e R 1f ) q3 —N(R j )C(O)N(R j ) 2 , and —(CR 1e R 1f ) q3 —CN;

R 1a , R 1b , R 1c , R 1d , R 1e , and R 1f , at each occurrence, are each independently hydrogen, halogen, alkyl,, or haloalkyl;

R g , at each occurrence, is independently hydrogen, alkyl, haloalkyl, G b , hydroxyalkyl, alkoxyalkyl, haloalkoxyl, or —(C 1 -C 6 alkylene)-G b ;

R h , at each occurrence, is independently alkyl, haloalkyl, G b , hydroxyalkyl, alkoxyalkl, haloalkoxy, or —(C 1 -C 6 alkylene)-G b ;

R j , at each occurrence, is independently hydrogen, alkyl, or haloalkyl;

R k , at each occurrence, is independently alkyl or haloalkyl;

A 1 is formula (a):

X 1 is CR 1 ;

X 2 is N;

X 3 is CR 3 ;

X 4 is N;

R 1 and R 3 can be the same or different, are each independently hydrogen, hydroxy, alkoxy, haloalkoxy, halogen, alkyl, or haloalkyl;

R 5 , at each occurrence, is the same or different, and is independently C 2 -C 10 alkyl, alkenyl, alkynyl, or haloalkyl;

q1, q2, and q3, at each occurrence, are each independently 1, 2, 3, 4, or 5; and

q4, at each occurrence, is independently 2, 3, 4, or 5.

2. The compound according to claim 1 or a pharmaceutically acceptable salt, solvate, or salt of a solvate thereof, wherein R x is phenyl and R 5 is C 2 -C 10 alkyl.

3. The compound according to claim 1 or a pharmaceutically acceptable salt, solvate, or salt of a solvate thereof, wherein R x is heteroaryl and R 5 is C 2 -C 10 alkyl.

4. The compound according to claim 1 or a pharmaceutically acceptable salt, solvate, or salt of a solvate thereof wherein R 5 is C 2 -C 10 alkyl or haloalkyl.

5. The compound according to claim 1 or a pharmaceutically acceptable salt, solvate, or salt of a solvate thereof, wherein R x is a phenyl or a heteroaryl wherein the heteroaryl is pyridinyl.

6. The compound according to claim 1 selected from the group consisting of

N-[(2Z)-1-butyl-7-hydroxy[1,3]thiazolo[5,4-d]pyrimidin-2(1H)-ylidene]-2-{[(S)-2-hyodroxypropyl]oxy}-5-(trifluoromethyl)benzamide;

N-[(2Z)-1-butyl[1,3]thiazolo[5,4-d]pyrimidin-2(1H)-ylidene]-2-{[(2S)-2-hydroxypropy]oxy}-5-(trifluoromethyl)benzamide; and

N-[(2Z)-1-butyl[1,3]thizolo[5,4-d]pyrimidin-2(1H)-ylidene]-6-chloro-4-(trifluoromethyl)pyridine-3-carboxamide;

a pharmaceutically acceptable salt, solvate, or salt of a solvate thereof.

7. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt, solvate, or salt of a solvate thereof; in combination with a pharmaceutically acceptable carrier.

8. A method for treating pain in a mammal in need of such treatment comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt, solvate, or salt of a solvate thereof.