IP Library › Granted Patent US 7,973,061
Granted Patent B2
US 7,973,061 · App. 10/598,911 · Granted Jul 5, 2011

Anaplastic lymphoma kinase modulators and methods of use

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Quick Facts
Patent No.
US 7,973,061
App. No.
10/598,911
Granted
Jul 5, 2011
Kind
B2
Abstract

The present invention relates to compounds of the Formula I, wherein L, X, Y, Z, R 1 , R 2 , R 3 and R 4 are defined herein. The invention also provides methods of using the compounds for inhibition of kinases, more specifically ALK kinases. The invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinase receptor signal transduction pathways related to the changes in cellular activities as mentioned above, and the invention includes compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions; (Formula I).

Claims (679)

1. A compound according to Formula I,

or a pharmaceutically acceptable salt, or hydrate thereof, wherein,

each of R 1 and R 2 is independently selected from —H, halogen, trihalomethyl, —CN, —NO 2 , —NH 2 , —NR 7 R 8 , —S(O) 0-2 R 7 , —SO 2 NR 7 R 7 , —CO 2 R 7 , —C(O)NR 7 R 7 , —N(R 7 )SO 2 R 7 , —N(R 7 )C(O)R 7 , —N(R 7 )CO 2 R 7 , —C(O)R 7 , optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl; or

combined, R 1 and R 2 are oxo;

R 3 is selected from —H, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl;

R 4 is —CH 2 —O-Ph, where Ph is an optionally substituted phenyl;

X is selected from —O—, —N(R a )—, and —S(O) 0-2 —;

Y is ═C(R b )— or ═N—;

one of Z is ═C(C(═O)W)—, while the other Z is ═C(R c )— or ═N—;

W is —N(R 5 )R 6 ;

L is selected from —C(═O)—;

R 5 is —H or R 6 ;

R 6 is optionally substituted aryl C 1-6 alkyl or optionally substituted heterocyclyl C 1-6 alkyl;

R 7 is —H or R 8 ;

R 8 is selected from optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl;

R 7 and R 8 , when taken together with a common nitrogen to which they are attached, form an optionally substituted five- to seven-membered heterocyclyl, said optionally substituted five- to seven-membered heterocyclyl optionally containing at least one additional annular heteroatom selected from N, O, S, and P; and

each of R a , R b , and R c is independently selected from —H, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl.

2. A compound according to claim 1 , wherein one of Z is —C(═O)W, while the other Z is ═C(R c )—.

3. A compound according to claim 2 , wherein X is —S(O) 0-2 — or —O—.

4. A compound according to claim 3 , wherein X is —S— or —O—.

5. A compound according to claim 4 , wherein Y is ═N—.

6. A compound according to claim 5 , wherein R 1 is —H.

7. A compound according to claim 6 , wherein R 2 is —H.

8. A compound according to claim 7 , wherein R 3 is —H.

9. A compound according to claim 5 , wherein R 5 is —H.

10. A compound according to claim 4 , wherein R 6 is optionally substituted aryl C 1-6 alkyl.

11. A compound according to claim 4 , wherein R 6 is optionally substituted heterocyclyl C 1-6 alkyl.

12. A compound according to claim 2 , wherein R c is —H.

13. A compound according to Formula II,

or a pharmaceutically acceptable salt, or hydrate thereof, wherein,

each of R 1 and R 2 is independently selected from —H, halogen, trihalomethyl, —CN, —NO 2 , —NH 2 , —NR 7 R 8 , —S(O) 0-2 R 7 , —SO 2 NR 7 R 7 , —N(R 7 )SO 2 R 7 , —N(R 7 )C(O)R 7 , —N(R 7 )CO 2 R 7 , —C(O)R 7 , optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl; or

combined, R 1 and R 2 are oxo;

R 3 is selected from —H, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl;

R 4 is —CH 2 —O-Ph, where Ph is optionally substituted phenyl;

X is selected from —O—, —N(R a )—, and —S(O) 0-2 —;

W is —N(R 5 )R 6 ;

L is selected from —C(═O)—;

R 5 is —H or R 6 ;

R 6 is optionally substituted aryl C 1-6 alkyl or optionally substituted heterocyclyl R 7 is —H or R 8 ;

R 8 is selected from optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl;

R 7 and R 8 , when taken together with a common nitrogen to which they are attached, form an optionally substituted five- to seven-membered heterocyclyl, said optionally substituted five- to seven-membered heterocyclyl optionally containing at least one additional annular heteroatom selected from N, O, S, and P; and

each of R a and R c is independently selected from —H, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl.

14. A compound according to claim 13 , wherein X is —S(O) 0-2 - or —O—.

15. A compound according to claim 14 , wherein X is —S— or —O—.

16. A compound according to claim 15 , wherein R 1 is —H.

17. A compound according to claim 16 , wherein R 2 is —H.

18. A compound according to claim 17 , wherein R 3 is —H.

19. A compound according to claim 13 , wherein R 5 is —H.

20. A compound according to claim 13 , wherein R 6 is optionally substituted C 1-6 alkyl.

21. A compound according to claim 13 , wherein R 6 is optionally substituted aryl C 1-6 alkyl.

22. A compound according to claim 13 , wherein R 6 is optionally substituted heterocyclyl C 1-6 alkyl.

23. A compound according to claim 13 , wherein R c is —H.

24. A compound selected from:

N-[2-(3-chlorophenyl)ethyl]-2-(1-{[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}ethyl)-

1,3-thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-{[4-(1,3-dihydro-2H-isoindol-2-ylcarbonyl)-1,3-thiazol-2-yl]methyl}-2-({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetamide

N-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylmethyl)-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(2-fluorophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-[(2R)-2-phenylpropyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-(2-phenylpropyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-[({[(4-ethylphenyl)amino]carbonyl}amino)methyl]-1,3-

thiazole-4-carboxamide

N-{2-[4-(methyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(4-ethylphenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-{[2,3-bis(methyloxy)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-N-[(1S,2S,3S,5R)-2,6,6-

trimethylbicyclo[3.1.1]hept-3-yl]-1,3-thiazole-4-carboxamide

N-{2-[4-(aminosulfonyl)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(3-fluorophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-[2-(2-methylphenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-[({[(4-iodophenyl)oxy]acetyl}amino)methyl]-1,3-thiazole-4-

carboxamide

N-{[2-(methyloxy)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(2,2-diphenylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[2-(2-thienyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-{2-[3-(ethyloxy)-4-(methyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(3-methylphenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

2-{[({[4-(1,1-dimethylethyl)phenyl]oxy}acetyl)amino]methyl}-N-{[2-

(methyloxy)phenyl]methyl}-1,3-thiazole-4-carboxamide

N-tricyclo[3.3.1.1~3,7~]dec-1-yl-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(4-fluorophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-{[({[4-(1-methylethyl)phenyl]amino}carbonyl)amino]methyl}-

1,3-thiazole-4-carboxamide

N-[(2S)-2-phenylpropyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[2-(2-fluorophenyl)ethyl]-2-{[({[4-(1-methylethyl)phenyl]amino}carbonyl)amino]methyl}-

1,3-thiazole-4-carboxamide

N-{2-[3-(ethyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

2-{[({[4-(1-methylethyl)phenyl]amino}carbonyl)amino]methyl}-N-{[2-

(methyloxy)phenyl]methyl}-1,3-thiazole-4-carboxamide

N-{2-[3,5-bis(methyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-oxazole-4-carboxamide

N-[(2-chlorophenyl)methyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-[2-(2,5-dimethylphenyl)ethyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-({2-[(difluoromethyl)oxy]phenyl}methyl)-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(2-cyclohex-1-en-1-ylethyl)-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(4-methylphenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-[3-(butyloxy)propyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylmethyl)-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

N-[(5-chloro-2-methylphenyl)methyl]-2({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{2-[3-(methyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{[2-(methylthio)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{2-[3,4-bis(methyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{2-[4-(ethyloxy)-3-(methyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(3,4-dichlorophenyl)ethyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(1H-indol-3-yl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-[(2,3-dimethylphenyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[(5-fluoro-2-methylphenyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(2-pyridin-4-ylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[2-(2,4-dimethylphenyl)ethyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-[({[4-(1-methylethyl)phenyl]acetyl}amino)methyl]-1,3-

thiazole-4-carboxamide

N-(2-pyridin-3-ylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-N-{2-[3-

(trifluoromethyl)phenyl]ethyl}-1,3-thiazole-4-carboxamide

N-{2-[2,3-bis(methyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(2-amino-2-oxo-1-phenylethyl)-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(2-fluorophenyl)ethyl]-2-{[({[4-(1-methylethyl)phenyl]oxy}acetyl)amino]methyl}-1,3-

thiazole-4-carboxamide

N-[2-(3,4-dimethylphenyl)ethyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-({2-[(trifluoromethyl)oxy]phenyl}methyl)-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{[2-(ethyloxy)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(2-fluorophenyl)ethyl]-2-[({[(4-iodophenyl)oxy]acetyl}amino)methyl]-1,3-thiazole-4-

carboxamide

N-{2-[2-(ethyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[(2,5-difluorophenyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{[4-({[2-(3-chlorophenyl)ethyl]amino}carbonyl)-1,3-thiazol-2-yl]methyl}-2-[(4-

chlorophenyl)oxy]pyridine-3-carboxamide

2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-N-{[2-

(trifluoromethyl)phenyl]methyl}-1,3-thiazole-4-carboxamide

N-[(2,4-dichlorophenyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(1-phenylpropyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[(4-{[4-(3,5-dichloropyridin-4-yl)piperazin-1-yl]carbonyl}-1,3-thiazol-2-yl)methyl]-2-({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetamide

N-[2-(3-chlorophenyl)ethyl]-2-{[({[4-(1,1-dimethylethyl)phenyl]oxy}acetyl)amino]methyl}-

1,3-thiazole-4-carboxamide

N-{2-[4-(ethyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[(3,5-dichlorophenyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

Nalpha-{[2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazol-4-

yl]carbonyl}-D-phenylalaninamide

N-{2-[(furan-2-ylmethyl)thio]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-{[({[4-(1-methylethyl)phenyl]oxy}acetyl)amino]methyl}-1,3-

thiazole-4-carboxamide

N-{[4-chloro-3-(trifluoromethyl)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[3-(propyloxy)propyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[(3,4-dichlorophenyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-cyclooctyl-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-

carboxamide

N-(2-pyridin-2-ylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-{[2,3-bis(methyloxy)phenyl]methyl}-2-{[({[4-(1-

methylethyl)phenyl]amino}carbonyl)amino]methyl}-1,3-thiazole-4-carboxamide

N-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{2-[2-(methyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(2-{[4-(methyloxy)phenyl]oxy}ethyl)-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

2-[({[(4-iodophenyl)oxy]acetyl}amino)methyl]-N-{[2-(methyloxy)phenyl]methyl}-1,3-

thiazole-4-carboxamide

N-[2-(4-chlorophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-[1-(phenylmethyl)piperidin-4-yl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(1-naphthalen-1-ylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-[1-(4-fluorophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-(2-methylcyclohexyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-N-[(1R,2R,3R,5S)-2,6,6-

trimethylbicyclo[3.1.1]hept-3-yl]-1,3-thiazole-4-carboxamide

2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-N-[(1S,2S,3S,5R)-2,6,6-

trimethylbicyclo[3.1.1]hept-3-yl]-1,3-oxazole-4-carboxamide

N-[2-(4-bromophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-[(1S)-2-oxo-1-(phenylmethyl)-2-pyrrolidin-1-ylethyl]-2-({[({4-

[(trifluoromethl)oxy]phenyl}oxy)acetyl]amino}methyl-1,3-thiazole-4-carboxamide

N-{2-[4-(aminosulfonyl)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

N-(2-{[(2,6-dichlorophenyl)methyl]thio}ethyl)-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(2-methylpropyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[(1S)-1-cyclohexylethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-{[4-(1,3,4,9-tetrahydro-2H-beta-carbolin-2-ylcarbonyl)-1,3-thiazol-2-yl]methyl}-2-({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetamide

N-{[2-chloro-5-(trifluoromethyl)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[(2-methylphenyl)methyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-(1-naphthalen-1-ylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-oxazole-4-carboxamide

N-{3-[(2-ethylhexyl)oxy]propyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

2-[({[(4-ethylphenyl)amino]carbonyl}amino)methyl]-N-[2-(2-fluorophenyl)ethyl]-1,3-

thiazole-4-carboxamide

2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-N-[(1S)-1,2,2-

trimethylpropyl]-1,3-thiazole-4-carboxamide

N-{(1S,2S)-2-[(phenylmethyl)oxy]cyclopentyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(2-chlorophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-[(1R,2R,4S)-bicyolo[2.2.1]hept-2-yl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{[2,6-bis(methyloxy)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{3-[methyl(phenyl)amino]propyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(1-phenylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

2-[({[(4-bromophenyl)oxy]acetyl}amino)methyl]-N-[2-(3-chlorophenly)ethyl]-1,3-thiazole-4-

carboxamide

2-[({[(4-ethylphenyl)amino]carbonyl}amino)methyl]-N-{[2-(methyloxy)phenly]methyl}-1,3-

thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-[({[(4-ethylphenyl)oxy]acetyl}amino)methyl]-1,3-thiazole-4-

carboxamide

N-{[2,5-bis(methyloxy)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-hexyl-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-

carboxamide

N-[2-(2-fluorophenyl)ethyl]-2-[({[4-(1-methylethyl)phenyl]acetyl}amino)methyl]-1,3-

thiazole-4-carboxamide

N-[(2,6-difluorophenyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[(2,3-difluorophenyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-{[(naphthalen-2-ylacetyl)amino]methyl}-1,3-thiazole-4-

carboxamide

2-{[({[4-(1-methylethyl)phenyl]oxy}acetyl)amino]methyl}-N-{[2-(methyloxy)phenyl]methyl}-

1,3-thiazole-4-carboxamide

N-[(3-chlorophenyl)methyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-{[2,4-bis(methyloxy)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{[3,5-bis(methyloxy)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(phenyloxy)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

1,1-dimethylethyl [5-({[2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazol-4-yl]carbonyl}amino)pentyl]carbamate

N-{2-[ethyl(3-methylphenyl)amino]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{[2,3-bis(methyloxy)phenyl]methyl}-2-{[({[4-(1-

methylethyl)phenyl]oxy}acetyl)amino]methyl}-1,3-thiazole-4-carboxamide

N-[(3,5-difluorophenyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[(3-fluorophenyl)methyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-[(2R)-2-phenylpropyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

oxazole-4-carboxamide

2-[(4-chlorophenyl)oxy]-N-{[4-({[2-(2-fluorophenyl)ethyl]amino}carbonyl)-1,3-thiazol-2-

yl]methyl}pyridine-3-carboxamide

N-{2-[({5-[(dimethylamino)methyl]furan-2-yl}methyl)thio]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-(2-phenyl-1-{[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}ethyl)-1,3-thiazole-4-carboxamide

N-(2-ethylbutyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[(3-methyl-2-thienyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{[2,3-bis(methyloxy)phenyl]methyl}-2-[({[(4-ethylphenyl)amino]carbonyl}amino)methyl]-

1,3-thiazole-4-carboxamide

N-[(5-methyl-3-phenylisoxazol-4-yl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-[({N-[(4-nitrophenyl)carbonyl]glycyl}amino)methyl]-1,3-

thiazole-4-carboxamide

N-{2-[2,5-bis(methyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(3-methylbutyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-{[4-(3,4-dihydroisoquinolin-2(1H)-ylcarbonyl)-1,3-thiazol-2-yl]methyl}-2-({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetamide

N-(4-methylcyclohexyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-{[4-({[2-(3-chlorophenyl)ethyl]amino}carbonyl)-1,3-thiazol-2-yl]methyl}-2-[(4-

fluorophenyl)oxy]pyridine-3-carboxamide

2-hydroxy-4-({[2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazol-4-

yl]carbonyl}amino)benzoic acid

N-[2-(2-fluorophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-oxazole-4-carboxamide

N-({4-[({[2,3-bis(methyloxy)phenyl]methyl}amino)carbonyl]-1,3-thiazol-2-yl}methyl)-2-[(4-

chlorophenyl)oxy]pyridine-3-carboxamide

N-(2-phenylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[2-(ethylthio)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-(1,1-diethylprop-2-yn-1-yl)-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(3-fluorophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-oxazole-4-carboxamide

N-[3-(methylthio)propyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[(4-chloro-2-methylphenyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(3-methylphenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-oxazole-4-carboxamide

N-(1-methyl-3-phenylpropyl)-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[(1S)-1,2-dimethylpropyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-{[3-(methyloxy)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{2-[3,4-bis(methyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-N-{[3-

(trifluoromethyl)phenyl]methyl}-1,3-thiazole-4-carboxamide

N-[(3-iodophenyl)methyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-{[2-fluoro-3-(trifluoromethyl)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(2-thienyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

oxazole-4-carboxamide

N-[2-(2,4-dichlorophenyl)ethyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-[({[(3-chlorophenyl)oxy]acetyl}amino)methyl]-1,3-thiazole-4-

carboxamide

N-[(1S)-1-(4-methylphenyl)ethyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{[2-chloro-6-(phenyloxy)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(2-thienylmethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[(2,4-dichloro-6-methylphenyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(diphenylmethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-[({[(4-methylphenyl)amino]carbonyl}amino)methyl]-1,3-

thiazole-4-carboxamide

N-[2-(2-fluorophenyl)ethyl]-2-{[(naphthalen-2-ylacetyl)amino]methyl}-1,3-thiazole-4-

carboxamide

N-[(4-methylphenyl)methyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-(1-ethylpropyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-(cyclohexylmethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-{[({[4-(methylthio)phenyl]amino}carbonyl)amino]methyl}-1,3-

thiazole-4-carboxamide

N-{[4-fluoro-3-(trifluoromethyl)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(3,3-dimethylbutyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-(2-cyclohex-1-en-1-ylethyl)-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

N-butyl-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-

carboxamide

N-{[4-(methyloxy)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(1-methylhexyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-(1-ethynylcyclohexyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-N-{2-[3-

(trifluoromethyl)phenyl]ethyl}-1,3-oxazole-4-carboxamide

N-(2,3-dihydro-1H-inden-1-yl)-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{(1S)-1-[4-(methyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-{[({[4-(ethyloxy)phenyl]amino}carbonyl)amino]methyl}-1,3-

thiazole-4-carboxamide

N-[(3,4-difluorophenyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{[2-(methylthio)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

N-{[3,4-bis(methyloxy)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

Nalpha-{[2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazol-4-

yl]carbonyl}-L-phenylalaninamide

N-(7-methyloctyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-(pyridin-2-ylmethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[(3-chloro-4-fluorophenyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

2-[({[4-(1-methylethyl)phenyl]acetyl}amino)methyl]-N-{[2-(methyloxy)phenyl]methyl}1,3-

thiazole-4-carboxamide

N-hexyl-N-methyl-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-(phenylmethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[2-(methylthio)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-(1,1,3,3-tetramethylbutyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-(1,2-dimethylpropyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

2-[(4-chlorophenyl)oxy]-N-({4-[({[2-(methyloxy)phenyl]methyl}amino)carbonyl]-1,3-thiazol-

2-yl}methyl)pyridine-3-carboxamide

N-(1,2,3,4-tetrahydronaphthalen-1-yl)-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(2-ethylhexyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[2-(4-fluorophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-oxazole-4-carboxamide

N~2~-{[2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazol-4-

yl]carbonyl}-D-leucinamide

N-{[2-(methyloxy)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

N-[1-(4-bromophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-(2-morpholin-4-ylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-[(4-fluorophenyl)methyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-{2-[3,5-bis(methyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-({[(3E)-4-phenylbut-3-enoyl]amino}methyl)-1,3-thiazole-4-

carboxamide

N-cyclohexyl-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-

carboxamide

N-(2-methylbutyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[2-(3,4-dimethylphenyl)ethyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

N-(1,5-dimethylhexyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-{2-[2-(phenyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

2-{[({[4-(butyloxy)phenyl]amino}carbonyl)amino]methyl}-N-{[2-(methyloxy)phenyl]methyl}-

1,3-thiazole-4-carboxamide

2-[({[(4-chlorophenyl)oxy]acetyl}amino)methyl]-N-[2-(2-fluorophenyl)ethyl]-1,3-thiazole-4-

carboxamide

N-(cyclopropylmethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-{[({[(1R,2S)-2-

phenylcyclopropyl]amino}carbonyl)amino]methyl}-1,3-thiazole-4-carboxamide

N-{(1R,2R)-2-[(phenylmethyl)oxy]cyclopentyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(2-pyridin-4-ylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

oxazole-4-carboxamide

N-(1-methylheptyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-{[4-({[2-(3-chlorophenyl)ethyl]amino}carbonyl)-1,3-thiazol-2-yl]methyl}-N~2~-

(phenylcarbonyl)methioninamide

N-(1,2-diphenylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-{[2,3-bis(methyloxy)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

N-{2-[4-(methyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

N-[2-(4-methylphenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-oxazole-4-carboxamide

N-(2,2-diphenylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

oxazole-4-carboxamide

N-[(4-chlorophenyl)methyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-cyclopentyl-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-

4-carboxamide

N-{[2-(methyloxy)phenyl]methyl}-2-{[(naphthalen-2-ylacetyl)amino]methyl}-1,3-thiazole-4-

carboxamide

N-{2-[3-(ethyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

N-[2-(4-bromophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-oxazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-[({[4-(methylthio)phenyl]acetyl}amino)methyl]-1,3-thiazole-4-

carboxamide

2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-N-[(1R)-1,2,2-

trimethylpropyl]-1,3-thiazole-4-carboxamide

N-{2-[3-(methyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

N-{[2-(ethyloxy)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

2-[({[1-(4-chlorophenyl)cyclopropyl]carbonyl}amino)methyl]-N-[2-(3-chlorophenyl)ethyl]-

1,3-thiazole-4-carboxamide

N-{[4-(dimethylamino)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(2-cyanoethyl)-N-hexyl-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

2-[({[(4-bromophenyl)oxy]acetyl}amino)methyl]-N-[2-(2-fluorophenyl)ethyl]-1,3-thiazole-4-

carboxamide

N-[(2S)-2-phenylpropyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

oxazole-4-carboxamide

N-(pyridin-3-ylmethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-(2-phenylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

oxazole-4-carboxamide

N-[(4-{[3-methyl-4-(4-methylphenyl)piperazin-1-yl]carbonyl}-1,3-thiazol-2-yl)methyl]-2-({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetamide

N-{[4-fluoro-2-(trifluoromethyl)phenyl]methyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-({4-[(4-propylpiperidin-1-yl)carbonyl]-1,3-thiazol-2-yl}methyl)-2-({4-

[trifluoromethyl)oxy]phenyl}oxy)acetamide

N-[2-(4-chlorophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-oxazole-4-carboxamide

N-[2-(1-methylpyrrolidin-2-yl)ethyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-{[2,3-bis(methyloxy)phenyl]methyl}-2-{[({[4-

(butyloxy)phenyl]amino}carbonyl)amino]methyl}-1,3-thiazole-4-carboxamide

N-(furan-2-ylmethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-{2-[3-(ethyloxy)-4-(methyloxy)phenyl]ethyl}-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

N-[2-(1H-indol-3-yl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-oxazole-4-carboxamide

N-{[4-(octahydroquinolin-1(2H)-ylcarbonyl)-1,3-thiazol-2-yl]methyl}-2-({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetamide

N-({4-[(3-methyl-4-phenylpiperazin-1-yl)carbonyl]-1,3-thiazol-2-yl}methyl)-2-({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetamide

1,1-dimethylethyl (1-{[2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazol-4-yl]carbonyl}piperidin-4-yl)carbamate

N-[(4-{[2R,6S)-2,6-dimethylmorpholin-4-yl]carbonyl}-1,3-thiazol-2-yl)methyl]-2-({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetamide

N-{[2,3-bis(methyloxy)phenyl]methyl}-2-{[(naphthalen-2-ylacetyl)amino]methyl}-1,3-

thiazole-4-carboxamide

N-(2-methylcyclohexyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl]oxy)acetyl]amino}methyl)-1,3-

oxazole-4-carboxamide

N-[(2,4-difluorophenyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-(2-phenylpropyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

oxazole-4-carboxamide

N-(3,3-diphenylpropyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[(2-chlorophenyl)methyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-oxazole-4-carboxamide

N-(1,4-dimethylpentyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

2-[({[(4-chlorophenyl)oxy]acetyl}amino)methyl]-N-{[2-(methyloxy)phenyl]methyl}-1,3-

thiazole-4-carboxamide

N-[(1S)-1-cyclohexylethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-oxazole-4-carboxamide

N-(tetrahydrofuran-2-ylmethyl)-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-({4-[(4aR,8aS)-octahydroisoquinolin-2(1H)-ylcarbonyl]-1,3-thiazol-2-yl}methyl)-2-({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetamide

N-(3-morpholin-4-ylpropyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-[1-methyl-2-(methyloxy)ethyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[3-(methyloxy)propyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N,N-diethyl-1-{[2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazol-

4-yl]carbonyl}piperidine-3-carboxamide

N-({4-[(4aS,8aS)-octahydroisoquinolin-2(1H)-ylcarbonyl]-1,3-thiazol-2-yl}methyl)-2-({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetamide

1-{[2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazol-4-

yl]carbonyl}piperidine-4-carboxamide

N-[2-(2-chlorophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-oxazole-4-carboxamide

N-(2-pyrrolidin-1-ylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-[(1-ethylpyrrolidin-2-yl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(2-fluorophenyl)ethyl]-2-({[(3E)-4-phenylbut-3-enoyl]amino}methyl)-1,3-thiazole-4-

carboxamide

2-[({[(4-bromophenyl)oxy]acetyl}amino)methyl]-N-{[2-(methyloxy)phenyl]methyl}-1,3-

thiazole-4-carboxamide

1,1-dimethylethyl (1-{[2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazol-4-yl]carbonyl}pyrrolidin-3-yl)carbamate

N-({4-[(4-pyridin-2-ylpiperazin-1-yl)carbonyl]-1,3-thiazol-2-yl}methyl)-2-({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetamide

N-(2,2,2-trifluoroethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[2-(acetylamino)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-thiazole-4-carboxamide

N-({4-[(3,5-dimethylpiperidin-1-yl)carbonyl]-1,3-thiazol-2-yl}methyl)-2-({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetamide

ethyl 4-({[2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazol-4-

yl]carbonyl}amino)piperidine-1-carboxylate

N-{[2-(methyloxy)phenyl]methyl}-2-({[(3E)-4-phenylbut-3-enoyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-(pyridin-4-ylmethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[3-(2-oxopyrrolidin-1-yl)propyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxamide

N-[2-(methyloxy)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[(2-methylphenyl)methyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-oxazole-4-carboxamide

N-({4-[(3-methylpiperidin-1-yl)carbonyl]-1,3-thiazol-2-yl}methyl)-2-({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetamide

N-(2-piperidin-1-ylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

thiazole-4-carboxamide

N-[(3,4-dichlorophenyl)methyl]-2-({[({4-

[(trifluoromethyl)oxy]phenyl]oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

N-[(4-fluorophenyl)methyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1,3-oxazole-4-carboxamide

N-(1,2,3,4-tetrahydronaphthalen-1-yl)-2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxamide

N-{[4-(octahydroisoquinolin-2(1H)-ylcarbonyl)-1,3-thiazol-2-yl]methyl}-2-({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetamide

1,1-dimethylethyl methyl(1-{[2-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazol-4-yl]carbonyl}pyrrolidin-

3-yl)carbamate

N-(2-pyridin-2-ylethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

oxazole-4-carboxamide

N-(phenylmethyl)-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-

oxazole-4-carboxamide

{4-[(trifluoromethyl)oxy]phenyl}methyl {[4-({[2-(3-chlorophenyl)ethyl]amino}carbonyl)-1,3-

thiazol-2-yl]methyl}carbamate

N-[2-(3-chlorophenyl)ethyl]-5-({[({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)isoxazole-3-carboxamide

2-(aminomethyl)-N-[2-(3-chlorophenyl)ethyl]-1,3-thiazole-4-carboxamide

(4E,6Z,8S,9S,10E,12S,13R,14R,16S,17R)-4,10,12,16-tetramethyl-8,13,14,17-

tetrakis(methyloxy)-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-

yl carbamate

2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-thiazole-4-carboxylic

acid

2-(aminomethyl)-N-{[2,3-bis(methyloxy)phenyl]methyl}-1,3-thiazole-4-carboxamide

2-(aminomethyl)-N-{[2-(methyloxy)phenyl]methyl}-1,3-thiazole-4-carboxamide

2-(aminomethyl)-N-[2-(2-fluorophenyl)ethyl]-1,3-thiazole-4-carboxamide

N-[2-(3-chlorophenyl)ethyl]-2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-

1H-imidazole-4-carboxamide

2-(aminomethyl)-N-[2-(3-chlorophenyl)ethyl]-1,3-oxazole-4-carboxamide

2-({[({4-[(trifluoromethyl)oxy]phenyl}oxy)acetyl]amino}methyl)-1,3-oxazole-4-carboxylic

acid

N-[2-(3-chlorophenyl)ethyl]-2-{[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]methyl}-1,3-

thiazole-4-carboxamide

N-[(4-{[4-ethyl-2-methyl-2-(3-methylbutyl)-1,3-oxazolidin-3-yl]carbonyl}-1,3-thiazol-2-

yl)methyl]-2-({4-[(trifluoromethyl)oxy]phenyl}oxy)acetamide; or

N-[(4-{[3-(diethylamino)pyrrolidin-1-yl]carbonyl}-1,3-thiazol-2-yl)methyl]-2-({4-

[(trifluoromethyl)oxy]phenyl}oxy)acetamide.

25. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable excipient or carrier.

26. The compound of claim 1 , wherein alkyl, aryl, and heterocyclyl, are substituted, one or more hydrogen atoms are replaced by a substituent independently selected from alkyl, aryl, arylalkyl, heterocyclylalkyl, heterocyclyl, alkoxy, alkylenedioxy, amino, alkylamino, dialkylamino, amidino, aryloxy, arylalkyloxy, carboxy, acyloxy, carboxyalkyl, carboxamido, benzyloxycarbonylamino, cyano, acyl, halogen, hydroxy, nitro, —S-alkyl, —S-aryl, —S-heterocyclyl, —S(O)—H, —S(O)-alkyl, —S(O)-aryl, —S(O)-heterocyclyl, —S(O 2 )—H, —S(O 2 )-alkyl, —S(O 2 )-aryl, —S(O 2 )-heterocyclyl, —S(O 2 )-alkoxy, —S(O 2 )-aryloxy, —S(O 2 )-heterocyclyloxy, thiol, halogen, hydroxy, oxo, carbamyl, acylamino, and sulfonamido.

27. The compound of claim 1 , wherein R 4 is —CH 2 —O-Ph, wherein the phenyl is substituted with —OCF 3 .

28. The compound of claim 1 , wherein R 4 is

29. The compound of claim 13 , wherein alkyl, aryl, and heterocyclyl, are substituted, one or more hydrogen atoms are replaced by a substituent independently selected from alkyl, aryl, arylalkyl, heterocyclylalkyl, heterocyclyl, alkoxy, alkylenedioxy, amino, alkylamino, dialkylamino, amidino, aryloxy, arylalkyloxy, carboxy, acyloxy, carboxyalkyl, carboxamido, benzyloxycarbonylamino, cyano, acyl, halogen, hydroxy, nitro, —S-alkyl, —S-aryl, —S-heterocyclyl, —S(O)—H, —S(O)-alkyl, —S(O)-aryl, —S(O)-heterocyclyl, —S(O 2 )—H, —S(O 2 )-alkyl, —S(O 2 )-aryl, —S(O 2 )-heterocyclyl, —S(O 2 )-alkoxy, —S(O 2 )-aryloxy, —S(O 2 )-heterocyclyloxy, thiol, halogen, hydroxy, oxo, carbamyl, acylamino, and sulfonamido.

30. The compound of claim 13 , wherein R 4 is —CH 2 —O-Ph, wherein the phenyl is substituted with —OCF 3 .

31. The compound of claim 1 , wherein R 4 is

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 18, 2006
From: LEAHY, JAMES WILLIAM; LEWIS, GARY LEE; NUSS, JOHN M.; RIDGWAY, BRIAN HUGH; SANGALANG, JOAN C.
To: EXELIXIS, INC.
Reel/Frame 018405/0211 →