IP Library Granted Patent US 9,193,713
Granted Patent B2
US 9,193,713 · App. 12/246,808 · Granted Nov 24, 2015

Compounds as cannabinoid receptor ligands

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Quick Facts
Patent No.
US 9,193,713
App. No.
12/246,808
Granted
Nov 24, 2015
Kind
B2
Abstract

The present invention relates compounds of formula (I) wherein A and R 1 are as defined in the specification, pharmaceutical compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and pharmaceutical compositions.

Claims (132)

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 2 is alkyl, haloalkyl, G 2 , —(CR x R y ) m -G 2 , —(CR x R y ) m —OR za , —(CR x R y ) m —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 , —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 ), —(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), (c), or (d)

R 21 , R 22 , R 23 , and R 24 are -alkylene-G 3 wherein G 3 , at each occurrence, is independently 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, and is optionally fused with a monocyclic ring selected from the group consisting of benzo, cycloalkyl, cycloalkenyl, heterocycle and heteroaryl; two non-adjacent atoms of each G 3 are 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, 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;

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, or haloalkyl;

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 8 , and R 9 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)R e , —C(O)O(R e ), —C(O)N(R e )(R g ), haloalkyl, —(CR i R k ) q —CN, —(CR j R k ) q —OR e , —(CR i 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 e )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, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycle, haloalkoxyalkyl, or haloalkyl; wherein 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, and haloalkyl;

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, 3or 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 21 , R 22 , R 23 , and R 24 are each independently tetrahydrofuranylmethyl, tetrahydropyranylmethyl, or oxazolidinylmethyl, and the tetrahydrofuranyl, oxazolidinyl, and the tetrahydropyranyl moieties are each independently unsubstituted or substituted.

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 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 alkyl.

12. The compound of claim 9 having formula (I), or a pharmaceutically acceptable salt thereof, wherein R 1 is phenyl or naphthyl, each of which is optionally substituted.

13. The compound of claim 2 having formula (I), or a pharmaceutically acceptable salt thereof, wherein ring A is formula (c).

14. The compound of claim 13 having formula (I), or a pharmaceutically acceptable salt thereof, wherein R 1 is phenyl or naphthyl, each of which is optionally substituted.

15. The compound of claim 2 having formula (I), or a pharmaceutically acceptable salt thereof, wherein ring A is formula (d).

16. 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;

5-chloro-2-methoxy-N-[(2E)-5-methyl-1-(tetrahydrofuran-2-ylmethyl)pyridin-2(1H)-ylidene]benzamide;

N-[5-tert-butyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]isoxazol-3(2H)-ylidene]-5-chloro-2-methoxybenzamide;

N-{5-tert-butyl-1-methyl-2-[(2S)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-chloro-2-methoxybenzamide; and

N-[5-tert-butyl-3-[(2R)-tetrahydrofuran-2-ylmethyl]-1,3-oxazol-2(3H)-ylidene]-5-chloro-2-methoxybenzamide.

17. 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 carrier.

18. 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 thereof.

19. A method for treating an inflammatory disorder 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 thereof.

20. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of

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}-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-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-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-methoxybenz amide;

N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-chloro-5-fluorobenz amide;

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-[(2E)-4-tert-butyl-1-[(2R)-tetrahydrofuran-2-ylmethyl]pyridin-2(1H)-ylidene]-5-chloro-2-methoxybenzamide;

N-[(2E)-4-tert-butyl-1-[(2R)-tetrahydrofuran-2-ylmethyl]pyridin-2(1H)-ylidene]-2-methoxy-5-(trifluoromethyl)benzamide;

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)-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,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 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′,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-(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;

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; and

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.

21. A method for treating an immune disorder 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 thereof, wherein the immune disorder is selected from the group consisting of multiple sclerosis, rheumatoid arthritis, systemic lupus, myasthenia gravis, type 1 diabetes, irritable bowel syndrome, psoriasis, psoriatic arthritis, hepatitis, tissue rejection in organ transplants, gluten-sensitive enteropathy (Celiac disease), asthma, chronic obstructive pulmonary disease, emphysema, bronchitis, acute respiratory distress syndrome, allergies, allergic rhinitis, dermatitis, and Sjogren's syndrome.

22. A method for treating Alzheimer's disease 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 thereof.

23. A method for treating a respiratory disorder 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 thereof, wherein the respiratory disorder is selected from the group consisting of pulmonary inflammation, chronic cough, asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis.

24. A method for treating a cardiovascular disorder 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 thereof, wherein the cardiovascular disorder is selected from the group consisting of atherosclerosis, ischemia, reperfusion, and myocardial infarction.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 17, 2013
From: ABBOTT LABORATORIES
To: ABBVIE INC.
Reel/Frame 030237/0588 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 29, 2008
From: CARROLL, WILLIAM A.; DART, MICHAEL J.; PEREZ MEDRANO, ARTURO; NELSON, DEREK W.; LI, TONGMEI; PEDDI, SRIDHAR; FROST, JENNIFER; KOLASA, TEODOZYJ; LIU, BO; LATSHAW, STEVEN P.; WANG, XUEQING
To: ABBOTT LABORATORIES
Reel/Frame 022033/0849 →