Compounds as cannabinoid receptor ligands
View Patent ↗Disclosed herein are compounds of formula (I) wherein Ring A and R 1 are as defined in the specification. Pharmaceutical compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and pharmaceutical compositions are also disclosed.
1. A compound according to formula (I),
or a pharmaceutically acceptable salt thereof, wherein
R 1 is alkyl, haloalkyl, G 1 , —(CR x R y ) m -G 1 , or —N(R 1a )(R z );
R z is alkyl, haloalkyl, G 2 , —(CR x R y ) m -G 2 , —(CR x R y ) n —OR za , —(CR x R y ) n —N(R za )(R zb )—(CR x R y ) m —C(O)O(R za ), —(CR x R y ) m —C(O)R za , —(CR x R y ) m —C(O)N(R za )(R zb ), —(CR x R y ) m —S(O) 2 O(R za ), —(CR x R y ) m —S(O) 2 R za , —(CR x R y ) m —S(O) 2 N(R za )(R zb ), or —(CR x R y ) m —CN;
G 1 and G 2 , at each occurrence, are each independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl; wherein each ring is independently unsubstituted or substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, —NO 2 , —CN, halogen, oxo, —OR e , —O—(CR j R k ) n —N(R w ) 2 , —OC(O)R e , —SR e , —SF 5 , —S(O)R f , —S(O) 2 R f , —S(O) 2 N(R e )(R g ), —N(R e )(R g ), —N(R g )C(O)R e , —N(R g )C(O)O(R f ), —N(R g )S(O) 2 R f , —N(R g )C(O)N(R e )(R g ), —N(R g )S(O) 2 N(R e )(R g ), —C(O)R e , —C(O)O(R e ), —C(O)N(R e )(R g ), alkoxyalkenyl, hydroxyalkenyl, haloalkyl, —(CR j R k ) q —CN, —(CR j R k ) q —OR e , —(CR j R k ) q —OC(O)R e , —(CR j R k ) q —SR e , —(CR j R k ) q —S(O)R f , —(CR j R k ) q —S(O) 2 R f , —(CR j R k ) q —N(R e )(R g ), —(CR j R k ) q —N(R g )C(O)R e , —(CR j R k ) q —N(R g )S(O) 2 R f , —(CR j R k ) q —N(R g )C(O)N(R e )(R g ), —(CR j R k ) q —N(R g )S(O) 2 N(R e )(R g ), —(CR j R k ) q —C(O)R e , —(CR j R k ) q —C(O)O(R e ), —(CR j R k ) q —C(O)N(R e )(R g ), —C(R w )═N—OR w , and morpholinyl;
Ring A represents formula (a), (b), or (d)
R 21 , R 22 , R 23 , and R 24 are -alkylene-G 3 wherein G 3 , at each occurrence, is independently furanyl, oxazolyl, isoxazolyl, oxadiazolyl, or a 4-, 5-, 6-, 7-, 8-, or 9-membered monocyclic heterocycle containing zero or one double bond, one or two oxygen, and zero or one nitrogen as ring atoms, wherein two non-adjacent atoms of said monocyclic heterocycle is optionally linked by an alkenylene bridge of 2, 3, or 4 carbon atoms, or optionally linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms; each G 3 ring is optionally fused with a monocyclic ring selected from the group consisting of benzo, cycloalkyl, cycloalkenyl, heterocycle, and heteroaryl; and each G 3 is independently unsubstituted or substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of oxo, alkyl, halogen, —OH, —O(alkyl), —O(haloalkyl), and haloalkyl;
R w , at each occurrence, is independently hydrogen or alkyl;
R 3 , R 6 , R 7 , R 8 , R 9 , R 11 , and R 12 are each independently hydrogen, alkyl, alkenyl, alkynyl, —NO 2 , —CN, halogen, —OR a , —N(R a )(R b ), —C(O)R a , —C(O)O(R a ), haloalkyl, —(CR c R d ) p —OR a , —(CR c R d ) p —N(R a )(R b ), —(CR c R d ) p —C(O)R a , —(CR c R d ) p —C(O)O(R a ), cycloalkyl, cycloalkenyl, or heterocycle;
R 4 and R 5 , are each independently hydrogen, alkyl, alkenyl, alkynyl, —NO 2 , —CN, halogen, —OR a , —N(R a )(R b ), —C(O)R a , —C(O)O(R a ), haloalkyl, —(CR c R d ) p —OR a , —(CR c R d ) p —N(R a )(R b ), —(CR c R d ) p —C(O)R a , —(CR c R d ) p —C(O)O(R a ), cycloalkyl, cycloalkenyl, or heterocycle; or R 4 and R 5 , together with the carbon atoms to which they are attached, form a monocyclic cycloalkyl ring which is optionally further substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, alkyl, haloalkyl, and oxo;
R a , R b , R 1a , R za , and R zb , at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
R x , at each occurrence, is independently hydrogen, halogen, alkyl, haloalkyl, or benzyl;
R y , R c , and R d , at each occurrence, are each independently hydrogen, halogen, alkyl, or haloalkyl;
X 1 and X 2 are independently O, S, or N(R 10 ) wherein R 10 is alkyl, alkoxyalkyl, haloalkoxyalkyl, or haloalkyl;
the cycloalkyl, cycloalkenyl, and heterocycle, as represented by R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 11 , and R 12 are each independently unsubstituted or substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, —NO 2 , —CN, halogen, oxo, —OR e , —OC(O)R e , —SR e , —S(O)R f , —S(O) 2 R f , —S(O) 2 N(R e )(R g ), —N(R e )(R g ), —N(R g )C(O)R e , —N(R g )S(O) 2 R f , —N(R g )C(O)N(R e )(R g ), —N(R g )S(O) 2 N(R e )(R g ), —C(O)R e , —C(O)O(R e ), —C(O)N(R e )(R g ), haloalkyl, —(CR j R k ) q —CN, —(CR j R k ) q —OR e , —(CR j R k ) q —OC(O)R e , —(CR j R k ) q —SR e , —(CR j R k ) q —S(O)R f , —(CR j R k ) q —S(O) 2 R f , —(CR j R k ) q —N(R e )(R g ), —(CR j R k ) q —N(R g )C(O)R e , —(CR j R k ) q —N(R g )S(O) 2 R f , —(CR j R k ) q —N(R g )C(O)N(R e )(R g ), —(CR j R k ) q —N(R g )S(O) 2 N(R e )(R g ), —(CR j R k ) q —C(O)R e , —(CR j R k ) q —C(O)O(R e ), and —(CR j R k ) q —C(O)N(R e )(R g );
R e and R g , at each occurrence, are each independently hydrogen, alkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycle, aryl, heteroaryl, haloalkoxyalkyl, or haloalkyl; wherein the aryl, the heteroaryl, the cycloalkyl, and the heterocycle moieties, by itself or as part of the substituents of R e and R g , are each independently unsubstituted or substituted with 1, 2, 3, 4, 5 or 6 substituents selected from the group consisting of alkyl, halogen, haloalkyl, hydroxy, oxo, ═N—O(H), ═N—O(alkyl), and alkoxy;
R f , at each occurrence, is independently alkyl or haloalkyl;
R j and R k , at each occurrence, are each independently hydrogen, halogen, alkyl, or haloalkyl;
m, p, and q, at each occurrence, are each independently 1, 2, 3, or 4; and
n is 2, 3 or 4.
2. The compound of claim 1 having formula (I), or a pharmaceutically acceptable salt thereof, wherein R 21 , R 22 , R 23 , and R 24 are -alkylene-G 3 ,
G 3 , at each occurrence, is independently a 4-, 5-, or 6-membered monocyclic heterocycle containing zero or one double bond, one or two oxygen, and zero or one nitrogen as ring atoms, and each G 3 is independently unsubstituted or substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of oxo, alkyl, halogen, —OH, —O (alkyl), —O (haloalkyl), and haloalkyl.
3. The compound of claim 2 having formula (I), or a pharmaceutically acceptable salt thereof, wherein G 3 , at each occurrence, is independently oxetanyl, oxazolidinyl, tetrahydrofuranyl, tetrahydropyranyl, 1,3-dioxalanyl, or 1,4-dioxanyl, each of which is independently unsubstituted or substituted.
4. The compound of claim 2 having formula (I), or a pharmaceutically acceptable salt thereof, wherein R 1 is G 1 or N(R 1a )(R z ).
5. The compound of claim 2 having formula (I), or a pharmaceutically acceptable salt thereof, wherein ring A is formula (a).
6. The compound of claim 5 having formula (I), or a pharmaceutically acceptable salt thereof, wherein X 1 is S.
7. The compound of claim 6 having formula (I), or a pharmaceutically acceptable salt thereof, wherein R 1 is G 1 , and G 1 is phenyl or naphthyl, each of which is optionally substituted.
8. The compound of claim 6 having formula (I), or a pharmaceutically acceptable salt thereof, wherein R 1 is —N(R 1a )(R z ).
9. The compound of claim 2 having formula (I), or a pharmaceutically acceptable salt thereof, wherein ring A is formula (b).
10. The compound of claim 9 having formula (I), or a pharmaceutically acceptable salt thereof, wherein X 2 is O.
11. The compound of claim 9 having formula (I), or a pharmaceutically acceptable salt thereof, wherein X 2 is N(R 10 ) and R 10 is C 1 -C 4 alkyl.
12. The compound of claim 9 having formula (I), or a pharmaceutically acceptable salt thereof, wherein R 1 is G 1 , and G 1 is phenyl or naphthyl, each of which is optionally substituted.
13. The compound of claim 9 having formula (I), or a pharmaceutically acceptable salt thereof, wherein R 1 is G 1 , and G 1 is optionally substituted cycloalkyl.
14. The compound of claim 2 having formula (I), or a pharmaceutically acceptable salt thereof, wherein ring A is formula (d).
15. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of
5-chloro-2-methoxy-N-[(2Z)-3-[(2R)-tetrahydrofuran-2-ylmethyl]-5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-thiadiazol-2(3H)-ylidene]benzamide;
5-chloro-N-[(2Z)-5-cyclopropyl-3-(tetrahydrofuran-2-ylmethyl)-1,3,4-thiadiazol-2(3H)-ylidene]-2-methoxybenzamide;
N-[(2Z)-5-cyclopropyl-3-(tetrahydrofuran-2-ylmethyl)-1,3,4-thiadiazol-2(3H)-ylidene]-2-ethoxybenzamide;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-5-chloro-2-methoxybenzamide;
5-chloro-2-methoxy-N-[(2Z)-5-(1-methylcyclopropyl)-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]benzamide;
5-chloro-N-[(2Z)-5-(1,1-dimethylprop-2-ynyl)-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-2-methoxybenzamide;
5-chloro-2-methoxy-N-[(2Z)-5-(2,2,3,3-tetrafluoro-1-methylcyclobutyl)-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]benzamide;
5-chloro-2-methoxy-N-[(2Z)-3-[(2R)-tetrahydrofuran-2-ylmethyl]-5-[1-(trifluoromethyl)cyclobutyl]-1,3,4-thiadiazol-2(3H)-ylidene]benzamide;
5-chloro-2-methoxy-N-[(2Z)-3-[(2R)-tetrahydrofuran-2-ylmethyl]-5-(2,2,2-trifluoro-1,1-dimethylethyl)-1,3,4-thiadiazol-2(3H)-ylidene]benzamide;
N-[(3E)-5-tert-butyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]isoxazol-3(2H)-ylidene]-5-chloro-2-methoxybenzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2S)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-chloro-2-methoxybenzamide;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3-oxazol-2(3H)-ylidene]-5-chloro-2-methoxybenzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-ethoxy-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-3-(pentafluoro-lambda-6-sulfanyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[(cis-3-hydroxycyclobutyl)methoxy]-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[(3-oxocyclobutyl)methoxy]-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[(cis-3-methoxycyclobutyl)methoxy]-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[(3,3-difluorocyclobutyl)methoxy]-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(3-methoxy-3-methylbutoxy)-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(2,2,2-trifluoroethoxy)-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(2-fluoroethoxy)-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(2-methoxyethoxy)-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-hydroxy-5-(trifluoromethyl)benzamide;
2-tert-butoxy-N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[2-(dimethylamino)ethoxy]-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(dimethylamino)-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-{[(2S)-2-methoxypropyl]oxy}-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(3-ethoxypropoxy)-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(3-methoxypropoxy)-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(2-ethoxyethoxy)-5-(trifluoromethyl)benzamide;
2-methoxy-N-[(3E)-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3(2H)-ylidene]-5-(trifluoromethyl)benzamide;
2-methoxy-N-{(3E)-1-methyl-5-(1-methylcyclopropyl)-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[(2-methoxyethyl)amino]-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(2,2-difluoroethoxy)-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[(3R)-tetrahydrofuran-3-yloxy]-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[(3S)-tetrahydrofuran-3-yloxy]-5-(trifluoromethyl)benzamide;
(E)-N-(5-tert-butyl-2-(((2R,3R)-3-fluorotetrahydrofuran-2-yl)methyl)-1-methyl-1H-pyrazol-3(2H)-ylidene)-2-methoxy-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[(2-fluoroethyl)amino]-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(2-fluoropropoxy)-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-{[(2R)-2-fluoropropyl]oxy}-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(2-fluoro-1-methylethoxy)-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(3-fluoro-3-methylbutoxy)-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[(1-hydroxycyclobutyl)methoxy]-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-chloro-2-methoxybenzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-fluoro-3-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-methoxy-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-cyano-2-methoxybenzamide;
5-bromo-N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-methoxybenzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-chloro-5-fluorobenzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2,3,5-trifluorobenzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-3-chloro-2-fluoro-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-3-chloro-2-methoxy-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-chloro-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-3,5-difluoro-2-methoxybenzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-3-chloro-2-(2-methoxyethoxy)-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-3-chloro-2-(2-fluoroethoxy)-5-(trifluoromethyl)benzamide;
5-bromo-N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(2-methoxyethoxy)benzamide;
5-bromo-N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(2-fluoroethoxy)benzamide;
5-bromo-N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2,3-dihydro-1-benzofuran-7-carboxamide;
N-[(3E)-5-tert-butyl-1-methyl-2-(tetrahydro-2H-pyran-2-ylmethyl)-1,2-dihydro-3H-pyrazol-3-ylidene]-2-methoxy-5-(trifluoromethyl)benzamide;
N-((3E)-5-tert-butyl-1-methyl-2-{[(5R)-5-methyltetrahydrofuran-2-yl]methyl}-1,2-dihydro-3H-pyrazol-3-ylidene)-2-methoxy-5-(trifluoromethyl)benzamide;
N-((3E)-5-tert-butyl-1-methyl-2-{[(5S)-5-methyltetrahydrofuran-2-yl]methyl}-1,2-dihydro-3H-pyrazol-3-ylidene)-2-methoxy-5-(trifluoromethyl)benzamide;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3-oxazol-2(3H)-ylidene]-2-methoxy-5-(trifluoromethyl)benzamide;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-N′-(4-methylcyclohexyl)urea;
N-(1-adamantylmethyl)-N′-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydro furan-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]urea;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-N′-{[(1S,2R,5S)-6,6-dimethylbicyclo [3.1.1]hept-2-yl]methyl}urea;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-N′-[1-(hydroxymethyl)-3-methylbutyl]urea;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-N′-(1,2-dimethylpropyl)urea;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-N′-(1-ethylpropyl)urea;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-N′-1,2,3,4-tetrahydronaphthalen-1-ylurea;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-N′-[(1S)-1-cyclohexylethyl]urea;
N-(tert-butyl)-N′-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]urea;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-N′-[(1S)-1-(hydroxymethyl)-2,2-dimethylpropyl]urea;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-N′-cycloheptylurea;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-N′-(2-ethylhexyl)urea;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-N′-(1-methyl-3-phenylpropyl)urea;
N-({[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]amino}carbonyl)-L-phenylalaninamide;
N 2 -({[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]amino}carbonyl)-L-isoleucinamide;
N 2 -({[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]amino}carbonyl)-N 1,3 -dimethyl-L-valinamide;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-N′-neopentylurea;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-N′-[(1S)-1-(hydroxymethyl)-2-methylpropyl]urea;
N-[(3E)-5-tert-butyl-1-methyl-2-(tetrahydrofuran-3-ylmethyl)-1,2-dihydro-3H-pyrazol-3-ylidene]-2-methoxy-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-methyl-5-(trifluoromethyl)benzamide;
N-{(3E)-4-bromo-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-methyl-5-(trifluoromethyl)benzamide;
2-bromo-N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[(1E)-3-methoxyprop-1-enyl]-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(3-methoxypropyl)-5-(trifluoromethyl)benzamide;
N-[(2Z)-5-tert-butyl-3-{[(4S)-2-oxo-1,3-oxazolidin-4-yl]methyl}-1,3,4-thiadiazol-2(3H)-ylidene]-5-chloro-2-methoxybenzamide;
2-(2-amino-2-methylpropoxy)-N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[(3-methylbut-2-enyl)oxy]-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[2-(1-hydroxycyclopentyl)ethoxy]-5-(trifluoromethyl)benzamide;
2-(azetidin-3-yloxy)-N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3-oxazol-2(3H)-ylidene]-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-3-fluoro-5-(trifluoromethyl)benzamide;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3,4-thiadiazol-2(3H)-ylidene]-2-{[(3S)-1-methylpyrrolidin-3-yl]oxy}-5-(trifluoromethyl)benzamide;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3-oxazol-2(3H)-ylidene]-2-{[(3S)-1-methylpyrrolidin-3-yl]oxy}-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[(1E)-prop-1-enyl]-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[(1E)-3-hydroxy-3-methylbut-1-enyl]-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(3-hydroxy-3-methylbutyl)-5-(trifluoromethyl)benzamide;
2-[(1-hydroxycyclobutyl)methoxy]-N-{(3E)-1-methyl-5-(1-methylcyclopropyl)-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-3-hydroxy-5-(trifluoromethyl)benzamide;
3-bromo-N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-3-(2-fluoro ethoxy)-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-3-nitro-5-(trifluoromethyl)benzamide;
3-amino-N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-(trifluoromethyl)benzamide;
N-[(2Z)-5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3-oxazol-2(3H)-ylidene]-2-[2-(dimethylamino)ethoxy]-5-(trifluoromethyl)benzamide;
2-[(Z)-(tert-butoxyimino)methyl]-N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-(methoxymethyl)-5-(trifluoromethyl)benzamide;
tert-butyl [2-[({(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}amino)carbonyl]-4-(trifluoromethyl)phenyl]acetate;
2-amino-N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[(methylsulfonyl)amino]-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-cyano-2-fluorobenzamide;
methyl 3-[({(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}amino)carbonyl]benzoate;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-chloro-2-fluorobenzamide;
methyl 4-[({(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}amino)carbonyl]bicyclo [2.2.1]heptane-1-carboxylate;
methyl 3-({[(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene]amino}carbonyl)adamantane-1-carboxylate;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-{[3-(hydroxyimino)cyclobutyl]methoxy}-5-(trifluoromethyl)benzamide;
tert-butyl 2-[({(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}amino)carbonyl]-4-(trifluoromethyl)phenylcarbamate;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-{[(dimethylamino)sulfonyl]amino}-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-(trifluoromethyl)-2-vinylbenzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-morpholin-4-yl-5-(trifluoromethyl)benzamide;
2-[bis(2-ethoxyethyl)amino]-N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-(trifluoromethyl)benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-[(isobutylsulfonyl)amino]-5-(trifluoromethyl)benzamide;
3-acetyl-N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}benzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-3-(methylsulfonyl)benzamide;
methyl [2-[({(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}amino)carbonyl]-4-(trifluoromethyl)phenyl]acetate;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-fluoro-5-nitrobenzamide;
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-3-cyanobenzamide;
ethyl 3-[2-[({(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}amino)carbonyl]-4-(trifluoromethyl)phenyl]propanoate; 5-bromo-N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-fluorobenzamide; and
N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-1-2-phenoxy-5-(trifluoromethyl)benzamide.
16. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, in combination with one or more pharmaceutically acceptable carriers.
17. A method for treating pain in a mammal in need of such treatment comprising administering to the mammal having pain a therapeutically effective amount of a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof.