Oxazole derivatives useful as inhibitors of FAAH

1. A method for treating a FAAH-mediated disease selected from the group consisting of osteoarthritis and pain, in a warm-blooded animal selected from the group consisting of a mouse, a rat, a horse, cattle, a sheep, a dog, and a cat, comprising administering to the warm-blooded animal an effective amount of a compound of Formula I

or a pharmaceutically acceptable salt thereof wherein:

X is S or SO;

n is 0, 1 or 2;

R 1 is selected from the group consisting of:

(1) aryl, and

(2) HET 1 ,

wherein R 1 is optionally mono or di-substituted with substituents R 4 and R 5 ; and wherein R 4 and R 5 are independently selected from the group consisting of:

(a) halo,

(b) —CN,

(c) mono, di or tri-halo C 1-4 alkyl,

(d) mono, di or tri-halo OC 1-4 alkyl,

(d) —OC 1-4 alkyl, optionally substituted with hydroxyl, halo or amino,

(e) —C 1-4 alkyl optionally substituted with one or two substituents selected from hydroxyl, CN, —CHF 2 and —CF 3 ,

(f) —C 1-2 alkyl-C 3-6 cycloalkyl optionally substituted with hydroxy, halo or CN,

(g) —S(O) n C 1-4 alkyl,

(h) —S(O) n NR 6 R 7 ,

(i) —C(O)—NH—NR 8 R 9 ,

(j) —C(O)—OH,

(k) —C(O)—OC 1-4 alkyl, optionally substituted with halo or hydroxy,

(l) —C(O)—NR 10 R 11 ,

(m) —C(O)—C 1-4 alkyl optionally mono, di or tri substituted with halo,

(o) —C(NR 12 )—NR 13 R 14 ,

(p) HET 4 ,

(q) aryl,

(r) —C(O)—NH—NH—C(O)H,

(s) —CH 2 —C(O)—O—C 1-4 alkyl, whereas the CH 2 may be optionally substituted with C 1-4 -alkyl or OH

(t) —CH 2 —C(O)NR 15 R 16 , whereas the CH 2 may be optionally substituted with C 1-4 -alkyl or OH, and

(u) —NR 17 R 18 ,

wherein choices (p) and (q) are each optionally mono or di-substituted with substituents selected from

(1) halo,

(2) —CN,

(3) —OH,

(4) —C 1-4 alkyl optionally substituted with hydroxy, halo or cyano,

(5) —CF 3 ,

(6) —OC 1-4 alkyl optionally substituted with hydroxyl or halo,

(7) —C(O)OH, and

(8) —C(O)O—C 1-3 alkyl;

(9) —C(O)—NR 19 R 20 ,

(10) —NH 2 ,

(11) Oxo,

(12) ═S,

with the proviso that the substituent on choice (q) is other than oxo or ═S,

wherein R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 and R 20 , are each independently selected from H and C 1-4 alkyl, or

R 6 and R 7 or R 8 and R 9 or R 10 and R 11 or R 13 and R 14 or R 15 and R 16 or R 17 and R 18 or R 19 and R 20 are joined together to form a ring with the atoms to which they are attached there is formed a 5-membered heterocyclic ring of 4 to 7 atoms, said ring containing 1, 2, 3 or 4 heteroatoms selected from N, O and S, said ring being optionally mono or di-substituted with substituents independently selected from halo, hydroxyl, oxo, C 1-4 alkyl, hydroxyC 1-4 alkyl, haloC 1-4 alkyl, —C(O)—C 1-4 alkyl and —S(O) n C 1-4 alkyl;

R 2 is selected from the group consisting of:

(1) aryl,

(2) HET 3 ,

(3) —CH 2 -aryl,

(4) —CH 2 -HET 3 , and

(5) —C 3-6 cycloalkyl,

wherein R 2 is optionally mono or di-substituted with substituents independently selected from the group consisting of

(a) halo,

(b) —CN,

(c) —OH,

(d) —C 1-4 alkyl optionally substituted with hydroxy, halo or cyano,

(e) —CF 3 ,

(f) —OC 1-4 alkyl optionally substituted with hydroxyl or halo,

(g) —C(O)O—C 1-3 alkyl and

(h) —S-aryl, optionally substituted with halo, C 1-4 alkyl or —OC 1-4 alkyl;

R 3 is selected from the group consisting of:

(1) HET 5 , and

(2) C 3-6 cycloalkyl,

wherein R 3 is optionally mono or di-substituted with substituents independently selected from the group consisting of

(a) hydroxy,

(b) halo,

(c) —C 3-6 cycloalkyl,

(d) —OC 3-5 cycloalkyl,

(e) —OC 1-4 alkyl,

(f) —C(O)CH 3

(g) mono, di or tri-halo C 1-4 alkyl,

(h) mono, di or tri-halo —OC 1-4 alkyl, and

(i) —S(O) n —C 1-4 alkyl;

wherein HET 1 , HET 2 , HET 3 , HET 4 and HET 5 are each independently a 5 to 10-membered aromatic, partially aromatic or non-aromatic mono- or bicyclic ring, or N-oxide thereof, said containing 1 to 4 heteroatoms selected from O, S and N, and optionally substituted with 1 to 2 oxo groups.

2. The method of claim 1

wherein:

R 1 is selected from the group consisting of:

(1) phenyl,

(2) pyridyl,

(3) pyridazinyl,

(4) pyrimidyl,

(5) pyrazinyl,

(6) thiazolyl,

(7) thienyl,

(8) pyrrolyl,

(9) oxazolyl, and

(10) oxadiazole;

wherein R 1 is optionally mono or di-substituted with substituents R 4 and R 5 , wherein R 4 and RS are independently selected from the group consisting of:

(a) halo,

(b) —CN,

(c) mono, di or tri-halo C 1-4 alkyl,

(d) —O—C 1-4 alkyl, optionally substituted with hydroxyl, halo or amino

(e) —C 1-4 alkyl optionally substituted with hydroxyl or CN,

(f) —C 1-2 alkyl-C 3-6 cycloalkyl optionally substituted with hydroxy,

(h) —S(O) n C 1-4 alkyl wherein n is 0, 1 or 2,

(i) —S(O) n NR 6 R 7 ,

(j) —C(O)—NR 10 R 11 ,

(k) HET 4 ,

(l) aryl, and

wherein choices (k) and (l) are each optionally mono or di-substituted with substituents selected from

(1) halo,

(2) —CN,

(3) —OH,

(4) —C 1-4 alkyl optionally substituted with hydroxy, halo or cyano,

(5) —CF 3 ,

(6) —OC 1-4 alkyl optionally substituted with hydroxyl or halo,

(7) —C(O)OH,

(8) —C(O)O—C 1-3 alkyl, and

(9) —C(O)—NR 19 R 20 ,

wherein R 6 , R 7 , R 10 , R 11 , R 19 and R 20 are each independently selected from H and C 1-4 alkyl.

3. The method of claim 2

wherein:

R 1 is selected from the group consisting of:

(1) phenyl,

(2) pyridyl,

(3) pyrimidyl,

(4) pyrazinyl,

(5) pyridazinyl,

(6) 1,2,4-oxadiazolyl, and

(7) 1,3,4-oxadiazolyl,

optionally mono or di-substituted with substituents R 4 and R 5 , which are independently selected from the group consisting of

(a) —C 1-4 alkyl optionally substituted with hydroxy,

(b) —S(O) n C 1-4 alkyl,

(c) —C(O)—NR 10 R 11 ,

(d) HET 4 , and

(e) halo,

wherein HET 4 is optionally mono or di-substituted with substituents selected from:

(1) halo,

(2) —CN,

(3) —OH,

(4) —C 1-4 alkyl optionally substituted with hydroxy, halo or cyano,

(5) —CF 3 ,

(6) —OC 1-4 alkyl optionally substituted with hydroxyl or halo,

(7) —C(O)OH, and

(8) —C(O)O—C 1-3 alkyl, and

(9) —C(O)—NR 19 R 20 ,

wherein R 10 , R 11 , R 19 and R 20 are each independently selected from H and C 1-4 alkyl.

4. The method of claim 1

wherein:

R 2 is selected from the group consisting of:

(1) aryl,

(2) HET 3 ,

(3) —CH 2 aryl, and

(4) —CH 2 HET 3 ,

wherein R 2 is optionally mono or di-substituted with substituents independently selected from the group consisting of:

(a) halo,

(b) —CN,

(c) —OH,

(d) —Hydroxy C 1-4 alkyl,

(e) —C 1-4 alkyl,

(f) —C 1-4 haloalkyl, and

(g) —OC 1-4 alkyl, optionally substituted with halo or hydroxyl.

5. The method of claim 4

wherein:

R 2 is selected from the group consisting of:

(1) aryl, and

(2) HET 3 ,

wherein R 2 is optionally mono or di-substituted with substituents independently selected from the group consisting of

(a) halo,

(b) —CN,

(c) —OH,

(d) -hydroxy C 1-4 alkyl,

(e) —CH 3 ,

(f) —CF 3 , and

(g) —OCH 3 .

6. The method of claim 5

wherein:

R 2 is selected from the group consisting of:

(1) phenyl,

(2) pyridyl,

(3) pyridazinyl,

(4) pyrimidyl,

(5) pyrazinyl,

(6) thiazolyl,

(7) oxazolyl,

(8) pyrazolyl,

(9) 1,2,4-oxadiazolyl, and

(10) 1,3,4-oxadiazolyl,

wherein R 2 is optionally mono or di-substituted with halo, OC 1-4 alkyl optionally substituted with halogen, —C 1-4 haloalkyl, hydroxyl and CN.

7. The method of claim 1 ,

wherein R 3 is HET 5 , and wherein HET 5 is optionally mono or di-substituted with substituents independently selected from the group consisting of:

(a) halo,

(b) —C 3-6 cycloalkyl,

(c) —OC 1-4 alkyl,

(d) mono, di or tri-halo C 1-4 alkyl, and

(e) mono, di or tri-halo —OC 1-4 alkyl.

8. The method of claim 7 ,

wherein R 3 is selected from the group consisting of:

(1) pyrimidinyl, and

(2) pyridyl,

wherein R 3 is optionally mono or di-substituted with halo, haloC 1-4 alkyl, or —OC 1-4 alkyl optionally substituted with halo.

9. The method of claim 1 wherein X is S.

10. The method of claim 1 , comprising administering a compound of Formula Ia

wherein

R 1 is selected from the group consisting of:

(1) phenyl,

(2) pyridyl,

(3) pyridazinyl,

(4) pyrimidyl,

(5) pyrazinyl,

(6) thiazolyl,

(7) thienyl,

(8) pyrrolyl,

(9) oxazolyl, and

(10) oxadiazole;

wherein R 1 is optionally mono or di-substituted with substituents R 4 and R 5 , which are independently selected from the group consisting of

(a) halo,

(b) —CN,

(c) mono, di or tri-halo C 1-4 alkyl,

(d) —O—C 1-4 alkyl, optionally substituted with hydroxyl, halo or amino

(e) —C 1-4 alkyl optionally substituted with hydroxyl or CN,

(f) —C 1-2 alkyl-C 3-6 cycloalkyl optionally substituted with hydroxy,

(h) —S(O) n C 1-4 alkyl wherein n is 0, 1 or 2,

(i) —S(O) n NR 6 R 7 ,

(j) —C(O)—NR 10 R 11 ,

(k) HET 4 , and

(l) aryl,

wherein choices (k) and (l) are each optionally mono or di-substituted with substituents selected from

(1) halo,

(2) —CN,

(3) —OH,

(4) —C 1-4 alkyl optionally substituted with hydroxy, halo or cyano,

(5) —CF 3 ,

(6) —OC 1-4 alkyl optionally substituted with hydroxyl or halo,

(7) —C(O)OH,

(8) —C(O)O—C 1-3 alkyl, and

(9) —C(O)—NR 19 R 20 ,

wherein R 6 , R 7 , R 10 , R 11 , R 19 and R 20 , are each independently selected from H and C 1-4 alkyl;

R 2 is selected from the group consisting of:

(1) aryl,

(2) HET 3 , and

(3) —C 3-6 cycloalkyl,

wherein choice R 2 is optionally mono or di-substituted with substituents independently selected from the group consisting of

(a) halo,

(b) —CN,

(c) —OH,

(d) -hydroxy C 1-4 alkyl,

(e) —C 1-4 alkyl,

(f) —C 1-4 haloalkyl, and

(g) —OC 1-4 alkyl, optionally substituted with halo or hydroxyl; and

R 3 is HET 5 , wherein HET 5 is optionally mono or di-substituted with substituents independently selected from the group consisting of

(a) halo,

(b) —C 3-6 cycloalkyl,

(c) —OC 1-4 alkyl,

(d) mono, di or tri-halo C 1-4 alkyl, and

(e) mono, di or tri-halo —OC 1-4 alkyl.

11. The method of claim 10 wherein

R 1 is selected from the group consisting of:

(1) phenyl,

(2) pyridyl,

(3) pyrimidyl,

(4) pyrazinyl,

(5) pyridazinyl,

(6) 1,2,4-oxadiazolyl, and

(7) 1,3,4-oxadiazolyl,

optionally mono or di-substituted with substituents R 4 and R 5 , which are independently selected from the group consisting of

(a) —C 1-4 alkyl optionally substituted with hydroxy,

(b) —S(O) n C 1-4 alkyl,

(c) —C(O)—NR 10 R 11 ,

(d) HET 4 , and

(e) halo,

wherein HET 4 is optionally mono or di-substituted with substituents selected from:

(1) halo,

(2) —CN,

(3) —OH,

(4) —C 1-4 alkyl optionally substituted with hydroxy, halo or cyano,

(5) —CF 3 ,

(6) —OC 1-4 alkyl optionally substituted with hydroxyl or halo,

(7) —C(O)OH, and

(8) —C(O)O—C 1-3 alkyl, and

(9) —C(O)—NR 19 R 20 ,

wherein R 10 , R 11 , R 19 and R 20 are each independently selected from H and C 1-4 alkyl,

R 2 is selected from the group consisting of:

(1) phenyl,

(2) pyridyl,

(3) pyridazinyl,

(4) pyrimidyl,

(5) pyrazinyl,

(6) thiazolyl,

(7) oxazolyl,

(8) pyrazolyl,

(9) 1,2,4-oxadiazolyl, and

(10) 1,3,4-oxadiazolyl,

wherein R 2 is optionally mono or di-substituted with halo, OC 1-4 alkyl optionally substituted with halogen, —C 1-4 haloalkyl, hydroxyl and CN; and

R 3 is selected from the group consisting of:

(1) pyrimidyl, and

(2) pyridyl,

wherein R 3 is optionally mono or di-substituted with halo, haloC 1-4 alkyl, or —OC 1-4 alkyl optionally substituted with halo.

12. The method of claim 1 , comprising administering a compound of Formula Ia

wherein:

R 1 is selected from the group consisting of:

(1) phenyl,

(2) pyridyl,

(3) pyridazinyl,

(4) pyrimidyl,

(5) pyrazinyl,

wherein R 1 is optionally mono or di-substituted with substituents R 4 and R 5 , which are independently selected from the group consisting of:

(a) halo,

(b) —CN,

(c) mono, di or tri-halo C 1-4 alkyl,

(d) —O—C 1-4 alkyl, optionally substituted with hydroxyl, halo or amino

(e) —C(CH 3 ) 2 —OH;

R 2 is selected from the group consisting of:

(1) phenyl,

(2) pyridyl,

(3) pyridazinyl,

(4) pyrimidyl,

(5) pyrazinyl,

(6) pyrazolyl,

wherein R 2 is optionally mono or di-substituted with halo, OC 1-4 alkyl optionally substituted with halogen, —C 1-4 haloalkyl, hydroxyl and CN; and

R 3 is selected from the group consisting of:

(1) pyrimidyl, and

(2) pyridyl,

wherein R 3 is optionally mono or di-substituted with halo, haloC 1-4 alkyl, or —OC 1-4 alkyl optionally substituted with halo.

13. The method of claim 12 wherein:

R 1 is selected from the group consisting of:

(1) phenyl,

(2) pyridyl,

(3) pyrazinyl,

wherein R 1 is optionally mono or di-substituted with substituents R 4 and R 5 , which are independently selected from the group consisting of:

(a) halo,

(b) —CN,

(c) mono, di or tri-halo C 1-4 alkyl,

(d) —O—C 1-4 alkyl, optionally substituted with hydroxyl, halo or amino

(e) —C(CH 3 ) 2 —OH;

R 2 is selected from the group consisting of:

(1) phenyl,

(2) pyridyl,

wherein R 2 is optionally mono or di-substituted with halo, OC 1-4 alkyl optionally substituted with halogen, —C 1-4 haloalkyl, hydroxyl and CN; and

R 3 is selected from the group consisting of:

(1) pyrimidyl, and

(2) pyridyl,

wherein R 3 is optionally mono or di-substituted with halo, haloC 1-4 alkyl, or —OC 1-4 alkyl optionally substituted with halo.

14. The method according to claim 1 wherein the compound is selected from the group consisting of:

(1) Methyl-5-[5-[(5-chloropyridin-2-yl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyrazine-2-carboxylate,

(2) Methyl 5-[5-[(5-chloropyridin-2-yl)thio]-2-(3-fluorophenyl)-1,3-oxazol-4-yl]pyrazine-2-carboxylate,

(3) 2-{5-[5-[(5-Chloropyridin-2-yl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyrazin-2-yl}propan-2-ol,

(4) 2-{5-[5-[(4-Chlorophenyl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyrazin-2-yl}propan-2-ol,

(5) 2-(5-{2-(4-Fluorophenyl)-5-[(4-methoxyphenyl)thio]-1,3-oxazol-4-yl}pyrazin-2-yl)propan-2-ol,

(6) 2-{5-[5-[(4-Chlorophenyl)thio]-2-(3-fluorophenyl)-1,3-oxazol-4-yl]pyrazin-2-yl}propan-2-ol,

(7) 2-(5-{2-(3-Fluorophenyl)-5-[(4-methoxyphenyl)thio]-1,3-oxazol-4-yl}pyrazin-2-yl)propan-2-ol,

(8) 2-{5-[5-[(5-Chloropyridin-2-yl)thio]-2-(3-fluorophenyl)-1,3-oxazol-4-yl]pyrazin-2-yl}propan-2-ol,

(9) 2-[5-[(4-Chlorophenyl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]-5-methylpyrazine,

(10) 2-{2-(3-Fluorophenyl)-5-[(4-methoxyphenyl)thio]-1,3-oxazol-4-yl}-5-methylpyrazine,

(11) 2-[5-[(4-Chlorophenyl)thio]-2-(3-fluorophenyl)-1,3-oxazol-4-yl]-5-methylpyrazine,

(12) 2-{5-[5-[(5-Chloropyridin-2-yl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyrazin-2-yl}propan-2-ol,

(13) 2-{5-[5-[(4-Chlorophenyl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

(14) 2-(5-{2-(4-Fluorophenyl)-5-[(4-methoxyphenyl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(15) 2-{5-[5-[(2,4-Difluorophenyl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

(16) 2-{5-[5-[(4-Chloro-2-fluorophenyl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

(17) 2-{5-[5-[(3,4-Difluorophenyl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

(18) 2-{5-[5-[(3-Fluoro-4-methoxyphenyl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

(19) 2-(5-{2-(4-Fluorophenyl)-5-[(5-fluoropyridin-2-yl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(20) 2-{5-[5-[(5-Chloropyrimidin-2-yl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

(21) 2-(5-{2-(4-Fluorophenyl)-5-[(6-methoxypyridin-3-yl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(22) 2-(5-{2-(4-Fluorophenyl)-5-[(5-fluoropyrimidin-2-yl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(23) 2-(5-{2-(4-Fluorophenyl)-5-[(5-methoxypyrimidin-2-yl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(24) 2-(5-{2-(4-Fluorophenyl)-5-[(2-methoxypyrimidin-5-yl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(25) 2-(5-{2-(4-Fluorophenyl)-5-[(5-methylpyridin-2-yl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(26) 2-{5-[5-[(5-Cyclopropylpyridin-2-yl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

(27) 2-(5-{2-(4-Fluorophenyl)-5-[(2,4,5-trifluorophenyl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(28) 2-{5-[5-[(4-Chloro-3-fluorophenyl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

(29) 2-{5-[5-[(4-Chlorophenyl)thio]-2-(3-fluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

(30) 2-(5-{2-(3-Fluorophenyl)-5-[(4-methoxyphenyl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(31) 2-{5-[5-[(5-Chloropyridin-2-yl)thio]-2-(3-fluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

(32) 2-{5-[5-[(5-Chloropyridin-2-yl)thio]-2-(3,5-difluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

(33) 2-(5-{2-(3,4-Difluorophenyl)-5-[(4-methoxyphenyl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(34) 2-{5-[5-[(4-Chlorophenyl)thio]-2-(3,4-difluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

(35) 2-{5-[5-[(5-Chloropyridin-2-yl)thio]-2-(3,4-difluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

(36) 2-{5-[5-[(5-Chloropyrimidin-2-yl)thio]-2-(3,4-difluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

(37) 2-{5-[5-[(5-Chloropyridin-2-yl)thio]-2-(4-fluoro-2-methylphenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

(38) 2-(5-{2-(4-Chlorophenyl)-5-[(5-chloropyridin-2-yl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(39) 2-(5-{2-(4-Chlorophenyl)-5-[(5-fluoropyridin-2-yl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(40) 2-(5-{2-(4-Chlorophenyl)-5-[(5-chloropyrimidin-2-yl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(41) 2-(5-{2-(4-chloro-3-fluorophenyl)-5-[(4-chlorophenyl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(42) 2-(5-{2-(4-chloro-3-fluorophenyl)-5-[(5-chloropyridin-2-yl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(43) 2-(5-{2-(3-chloro-4-fluorophenyl)-5-[(4-chlorophenyl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(44) 2-(5-{2-(3-chloro-4-fluorophenyl)-5-[(5-chloropyridin-2-yl)thio]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(45) 2-{6-[5-[(5-Chloropyridin-2-yl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyridin-3-yl}propan-2-ol,

(46) 2-{6-[5-[(4-chlorophenyl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyridin-3-yl}propan-2-ol,

(47) 4-[5-[(4-Chlorophenyl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]benzonitrile,

(48) 3-{4-[5-[(4-Chlorophenyl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]phenyl}-1,2,4-oxadiazole,

(49) 4-{5-[(5-Chloropyridin-2-yl)thio]-4-[6-(1-hydroxy-1-methylethyl)pyridin-3-yl]-1,3-oxazol-2-yl}benzonitrile,

(50) 2-(5-{5-[(4-chlorophenyl)thio]-2-pyridin-2-yl-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(51) 2-(5-{5-[(5-chloropyridin-2-yl)thio]-2-pyridin-2-yl-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(52) 3-(4-{5-[(4-Chlorophenyl)thio]-2-phenyl-1,3oxazol-4-yl}phenyl)-1,2,4oxadiazole,

(53) 2-(4-{5-[(4-Chlorophenyl)thio]-2-phenyl-1,3oxazol-4-yl}phenyl)-1,3,4oxadiazole,

(54) 5-[(4-chlorophenyl)thio]-4-[4-(methylsulfonyl)phenyl]-2-phenyl-1,3-oxazole, and

(55) 2-{5-[(4-chlorophenyl)thio]-4-[4-(methylsulfonyl)phenyl]-1,3-oxazol-2-yl}pyridine, and

(56) 2-{5-[5-[(5-Chloropyridin-2-yl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol;

or a pharmaceutically acceptable salt thereof.

15. The method according to claim 1 , wherein the compound is selected from the group consisting of

(1) 5-Chloro-2-({2-(4-fluorophenyl)-4-[6-(1,2,4-oxadiazol-3-yl)pyridin-3-yl]-1,3-oxazol-5-yl}sulfanyl)pyridine,

(2) 5-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}pyrimidine-2-carbonitrile,

(3) 1-(5-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}pyrimidin-2-yl)ethanone,

(4) 2-(5-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}pyrimidin-2-yl)propan-2-ol,

(5) 5-Chloro-2-({2-(4-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-1,3-oxazol-5-yl}sulfanyl)pyridine,

(6) Methyl-4-{5-[(5-chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}benzoate,

(7) 2-(4-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}phenyl)propan-2-ol,

(8) 4-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}-1-(methylsulfonyl)piperidinium trifluoroacetate,

(9) Methyl 2-(5-{5-[(5-chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}pyridin-2-yl)-2-methylpropanoate,

(10) 3-(5-{5-[(5-chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}pyridin-2-yl)-2,3-dimethylbutan-2-ol

(11) 2-(5-{5-[(5-chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}pyridin-2-yl)-2-methylpropan-1-ol,

(12) Methyl 5-{5-[(5-chloropyridin-2-yl)sulfanyl]-2-cyclopropyl-1,3-oxazol-4-yl}pyridine-2-carboxylate,

(13) 1-(5-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-cyclopropyl-1,3-oxazol-4-yl}pyridin-2-yl)ethanone,

(14) 2-(5-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-cyclopropyl-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(15) 2-(6-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}pyridazin-3-yl)propan-2-ol,

(16) Ethyl 5-{5-[(5-chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl} isoxazole-3-carboxylate,

(17) 2-(5-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}isoxazol-3-yl)propan-2-ol,

(18) Methyl 2-{5-[(5-chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}-1,3-thiazole-4-carboxylate,

(18) 2-(2-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}-1,3-thiazol-4-yl)propan-2-ol,

(19) 5-Chloro-2-({2-cyclopropyl-4-[6-(methylsulfonyl)pyridin-3-yl]-1,3-oxazol-5-yl}sulfanyl)pyridine,

(20) 5-Chloro-2-({2-(4-fluorophenyl)-4-[6-(methylsulfonyl)pyridin-3-yl]-1,3-oxazol-5-yl}sulfanyl)pyridine,

(21) 5-Chloro-2-({2-(4-fluorophenyl)-4-[6-(methylsulfonyl)pyridin-3-yl]-1,3-oxazol-5-yl}sulfanyl)pyrimidine,

(22) (R)-5-Chloro-2-({2-(4-fluorophenyl)-4-[6-(methylsulfinyl)pyridin-3-yl]-1,3-oxazol-5-yl}sulfanyl)pyridine,

(23) (5)-5-Chloro-2-({2-(4-fluorophenyl)-4-[6-(methylsulfinyl)pyridin-3-yl]-1,3-oxazol-5-yl}sulfanyl)pyridine,

(24) (R)-5-Fluoro-2-({2-(4-fluorophenyl)-4-[6-(methylsulfinyl)pyridin-3-yl]-1,3-oxazol-5-yl}sulfanyl)pyridine,

(25) (S)-5-Fluoro-2-({2-(4-fluorophenyl)-4-[6-(methylsulfinyl)pyridin-3-yl]-1,3-oxazol-5-yl}sulfanyl)pyridine,

(26) Methyl 5-(5-[(4-chlorophenyl)sulfanyl]-2-(1-ethyl-1H-pyrazol-4-yl)-1,3-oxazol-4-yl)pyridine-2-carboxylate,

(27) 2-(5-{5-[(4-chlorophenyl)sulfanyl]-2-(1-ethyl-1H-pyrazol-4-yl)-1,3-oxazol-4-yl)pyridin-2-yl}propan-2-ol,

(28) Methyl 5-{5-[(5-chloropyridin-2-yl)sulfanyl]-2-(1-ethyl-1H-pyrazol-4-yl}-1,3-oxazol-4-yl)pyridine-2-carboxylate,

(29) 2-(5-{5-[(5-chloropyridin-2-yl)sulfanyl]-2-(1-ethyl-1H-pyrazol-4-yl)-1,3-oxazol-4-yl}pyridin-2-yl}propan-2-ol,

(30) 5-Chloro-2-({2-(4-fluorophenyl)-4-[6-(methylsulfanyl)pyridin-3-yl]-1,3-oxazol-5-yl}sulfanyl)pyridine,

(31) Methyl 5-{5-[(5-chloropyridin-2-yl)sulfanyl]-2-cyclobutyl-1,3-oxazol-4-yl}pyridine-2-carboxylate,

(32) 2-(5-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-cyclobutyl-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(33) 1-(5-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-cyclobutyl-1,3-oxazol-4-yl}pyridin-2-yl)ethanone,

(34) (R)-1-(5-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-cyclobutyl-1,3-oxazol-4-yl}pyridin-2-yl)ethanol,

(35) (S)-1-(5-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-cyclobutyl-1,3-oxazol-4-yl}pyridin-2-yl)ethanol,

(36) Methyl 5-{2-(5-chloropyridin-3-yl)-5-[(5-chloropyridin-2-yl)sulfanyl]-1,3-oxazol-4-yl}pyridine-2-carboxylate,

(37) 2-(5-{2-(5-Chloropyridin-3-yl)-5-[(5-chloropyridin-2-yl)sulfanyl]-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(38) 1-(5-{2-(5-Chloropyridin-3-yl)-5-[(5-chloropyridin-2-yl)sulfanyl]-1,3-oxazol-4-yl}pyridin-2-yl)ethanone,

(39) (5-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}pyridin-2-yl)acetonitrile,

(40) 1-(5-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}pyridin-2-yl)-3-hydroxycyclobutanecarbonitrile,

(41) 2-(5-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-(4-fluorobenzyl)-1,3-oxazol-4-yl}pyridin-2-yl)propan-2-ol,

(42) Methyl 2-{5-[(5-chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}pyrimidine-5-carboxylate,

(43) 6-{5-[(4-Chlorophenyl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}-3,4-dihydroisoquinolin-1(2H)-one,

(44) 7-{5-[(4-Chlorophenyl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}-3-(difluoromethyl)quinoline,

(45) 6-{5-[(4-Chlorophenyl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}-2-(difluoromethyl)quinoline,

(46) 6-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}-N,N-dimethylquinoline-2-carboxamide,

(47) 3-{5-[(5-Chloropyridin-2-yl)sulfanyl]-2-(4-fluorophenyl)-1,3-oxazol-4-yl}-6-(methylsulfonyl)pyridazine, and

(48) (1S,2S)-2-(4-{5-[(5-chloropyridin-2-yl)thio]-2-cyclopropyl-1,3-oxazol-4-yl}phenyl)-N,N-dimethylcyclopropanecarboxamide, and

(49) 2-{5-[5-[(5-Chloropyridin-2-yl)thio]-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl}propan-2-ol,

or a pharmaceutically acceptable salt thereof.

16. The method of claim 1 , wherein the compound is selected from a compound having the formula

R 2

R 3

or

R 1

R 3

or

R 1

R 3

or

R 1

R 2

Or

R 3

or a pharmaceutically acceptable salt thereof.

17. The method of claim 1 wherein the compound is

or a pharmaceutically acceptable salt thereof.

18. The method of claim 1 , wherein the pain is skeletomuscular pain or acute pain.

19. The method of claim 1 , wherein the warm-blooded animal is a dog.