Monocyclic Heteroaryl compounds

1. A compound of the Formula:

or a tautomer or a pharmaceutically acceptable salt thereof, wherein:

Ring T represents

Ring A represents a 5- or 6-membered aryl or heteroaryl ring;

Ring B represents a 5- or 6-membered aryl or heteroaryl ring;

L 1 is NR 1 C(O) or C(O)NR 1 ;

each R a and R t is independently selected from halo, —CN, —NO 2 , —R 4 , —OR 2 , —NR 2 R 3 , —C(O)YR 2 , —OC(O)YR 2 , —NR 2 C(O)YR 2 , —SC(O)YR 2 , —NR 2 C(═S)YR 2 , —OC(═S)YR 2 , —C(═S)YR 2 , —YC(═NR 3 )YR 2 , —YP(═O)(YR 4 )(YR 4 ), —Si(R 4 ) 3 , —NR 2 SO 2 R 2 , —S(O) r R 2 , —SO 2 NR 2 R 3 and —NR 2 SO 2 NR 2 R 3 , wherein Y is independently a bond, —O—, —S— or —NR 3 —;

each R 1 , R 2 and R 3 is independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocycle and heteroaryl, and in addition, NR 2 R 3 may be a 5- or 6-membered saturated, partially saturated or unsaturated ring, which is optionally substituted and contains 0-2 additional heteroatoms selected from N, O and S(O) r ;

each R 4 is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocyclic and heteroaryl;

R b is selected from halo, —CN, —NO 2 , —R 4 , —OR 2 , —NR 2 R 3 , —C(O)YR 2 , —OC(O)YR 2 , —NR 2 C(O)YR 2 , —SC(O)YR 2 , —NR 2 C(═S)YR 2 , —OC(═S)YR 2 , —C(═S)YR 2 , —YC(═NR 3 )YR 2 , —YP(═O)(YR 4 )(YR 4 ), —Si(R 4 ) 3 , —NR 2 SO 2 R 2 , —S(O) r R 2 , —SO 2 NR 2 R 3 , and —NR 2 SO 2 NR 2 R 3 , Ring C, and —L 2 -Ring D, wherein Y is independently a bond, —O—, —S— or —NR 3 —;

in which:

(i) Ring C is a 5- or 6-membered heteroaryl or heterocyclic ring comprising carbon atoms and 1-3 heteroatoms independently selected from O, N and S(O) r and which is optionally substituted with 1 to 5 substituents, R c ;

(ii) L 2 is (CH 2 ) z , O(CH 2 ) x , NR 3 (CH 2 ) x , S(CH 2 ) x , and (CH 2 ) x NR 3 C(O)(CH 2 ) x , oriented in either direction; and,

(iii) Ring D is a 5- or 6-membered heterocyclic or heteroaryl ring comprising carbon atoms and 1-3 heteroatoms independently selected from O, N and S(O) r and which is optionally substituted with 1 to 5 R d substituents;

each R c and R d is independently halo, ═O, ═S, —CN, —NO 2 , —R 4 , —OR 2 , —NR 2 R 3 , —Si(R 4 ) 3 , —C(O)YR 2 , —OC(O)YR 2 , —NR 2 C(O)YR 2 , —SC(O)YR 2 , —NR 2 C(═S)YR 2 , —OC(═S)YR 2 , —C(═S)YR 2 , —YC(═NR 3 )YR 2 , —YP(═O)(YR 4 ) 2 , —NR 2 SO 2 R 2 , —S(O) r R 2 , —SO 2 NR 2 R 3 or —NR 2 SO 2 NR 2 R 3 ;

each of the foregoing alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocyclic and heteroaryl moieties is optionally substituted;

m is 0, 1, 2, 3 or 4;

n is 0, 1, 2 or 3;

p is 1, 2, 3, 4 or 5;

r is 0, 1 or 2;

x is 0, 1, 2 or 3;

z is 1, 2, 3 or 4;

each optional substituent for an unsaturated carbon atom of an aryl or heteroaryl moiety and for a carbon atom of an alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl or non-aromatic heterocyclic group is selected from F, Cl, Br, I, —CN, —R 4 , —OR 2 , —S(O) r R 2 , —SO 2 NR 2 R 3 , —NR 2 R 3 , —(CO)YR 2 , —O(CO)YR 2 , —NR 2 (CO)YR 2 , —S(CO)YR 2 , —NR 2 C(═S)YR 2 , —OC(═S)YR 2 , —C(═S)YR 2 , —YC(═NR 3 )Y′R 2 , —COCOR 2 , —COMCOR 2 , —YP(═O)(YR 4 )(YR 4 ), —Si(R 2 ) 3 , —NO 2 , —NR 2 SO 2 R 2 and —NR 2 SO 2 NR 2 R 3 , where M is a 1-6 carbon alkyl group;

each optional substituent for an alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl or non-aromatic heterocyclic group alternatively is selected from ═O, ═S, ═NH, ═NNR 2 R 3 , ═NNHC(O)R 2 , ═NNHCO 2 R 2 , and ═NNHSO 2 R 2 ; and

each optional substituent on a nitrogen is selected from R 4 , —NR 2 R 3 , —C(═O)R 2 , —C(═O)OR 2 , —C(═O)SR 2 , —C(═O)NR 2 R 3 , —C(═NR 2 )NR 2 R 3 , —C(═NR 2 )OR 2 , —C(═NR 2 )R 3 , —COCOR 2 , —COMCOR 2 , —CN, —SO 2 R 3 , S(O)R 3 , —P(═O)(YR 2 )(YR 2 ), —NR 2 SO 2 R 3 and —NR 2 SO 2 NR 2 R 3 .

2. The compound of claim 1 , wherein at least one of Rb is

or a tautomer or a pharmaceutically acceptable salt thereof, wherein:

v is 0, 1, 2, 3, 4 or 5.

3. The compound according to claim 2 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein Ring C is a heteroaryl ring bearing a single C 1 -C 6 alkyl substituent.

4. The compound of claim 3 or a tautomer or a pharmaceutically acceptable salt thereof, in which Ring C is selected from the following:

5. The compound according to claim 2 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein Ring C is one of the following:

6. The compound of claim 2 , or a tautomer or a pharmaceutically acceptable salt thereof, having the formula:

7. The compound of claim 6 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein R t is —CH 3 or —C(O)NH 2 , v is 1, n is 0 or 1, m is 1, t is 1, R a is —CH 3 , R b is CF 3 and R c is —CH 3 .

8. The compound according to claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein Rings A and B are aryl.

9. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein at least one of R b is

wherein:

Ring D represents a 5- or 6-membered heterocyclic or heteroaryl ring, comprising carbon atoms and 1-3 heteroatoms independently selected from N, O, S(O) r ;

L 2 is (CH 2 ) z , O(CH 2 ) x , NR 3 (CH 2 ) x , S(CH 2 ) x or (CH 2 ) x NR 3 C(O)(CH 2 ) x and the linkage unit can be used in either direction;

R d , at each occurrence, is selected from the group consisting of halo, ═O, ═S, —CN, —NO 2 , —R 4 , —OR 2 , —NR 2 R 3 , —C(O)YR 2 , —OC(O)YR 2 , —NR 2 C(O)YR 2 , —SC(O)YR 2 , —NR 2 C(═S)YR 2 , —OC(═S)YR 2 , —C(═S)YR 2 , —YC(═NR 3 )YR 2 , —YP(═O)(YR 4 )(YR 4 ), —Si(R 4 ) 3 , —NR 2 SO 2 R 2 , —S(O) r R 2 , —SO 2 NR 2 R 3 and —NR 2 SO 2 NR 2 R 3 , wherein Y is independently a bond, —O—, —S— or —NR 3 —;

R 2 and R 3 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocyclic and heteroaryl;

alternatively, NR 2 R 3 moiety may be a 5- or 6-membered saturated, partially saturated or unsaturated ring, which can be optionally substituted and which contains 0-2 additional heteroatoms selected from N, O and S(O) r ;

each occurrence of R 4 is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocyclic and heteroaryl;

each of the foregoing alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl and heterocycle moieties is optionally substituted;

w is 0, 1, 2, 3, 4 or 5;

x is 0, 1, 2 or 3;

z is 1, 2, 3 or 4; and

t is 0, 1, 2, 3, or 4.

10. The compound according to claim 9 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein Rings A and B are aryl.

11. The compound of claim 9 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein Ring D is a substituted or unsubstituted piperazine ring and L 2 is CH 2 .

12. The compound of claim 11 , or a tautomer or a pharmaceutically acceptable salt thereof, having the formula:

13. The compound of claim 12 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein R t is independently selected from —CH 3 and —C(O)NH 2 , n is 0 or 1, m is 1, t is 1, R a is methyl, R b is CF 3 , and R d is selected from methyl and CH 2 CH 2 OH.

14. The compound of claim 9 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein Ring D is a substituted or unsubstituted heteroaryl ring.

15. The compound of claim 9 or a tautomer or a pharmaceutically acceptable salt thereof, in which Ring B-L 2 -Ring D is selected from the following:

16. The compound of claim 1 or a tautomer or a pharmaceutically acceptable salt thereof, in which Ring T is selected from:

17. The compound of claim 1 or a tautomer or a pharmaceutically acceptable salt thereof, in which Ring T is selected from the following:

18. The compound of claim 1 or a tautomer or a pharmaceutically acceptable salt thereof, in which Ring A is selected from the following:

19. The compound of claim 1 or a tautomer or a pharmaceutically acceptable salt thereof, in which Ring B is selected from the following:

20. A compound selected from the following:

or a pharmaceutically acceptable salt thereof.

21. A compound selected from the following:

1-Methyl-5-(2-methyl-5-[4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenylcarbamoyl]-phenylethynyl)-1H-imidazole-2-carboxylic acid amide,

1-Methyl-5-(2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenylcarbamoyl]-phenylethynyl)-1H-imidazole-2-carboxylic acid amide,

5-[5-(3-Imidazol-1-yl-5-trifluoromethylphenylcarbamoyl)-2-methyl-phenylethynyl]-1-methyl-1H-imidazole-2-carboxylic acid amide,

N-{3-chloro-4-[(4-methylpiperazin-1-yl)methyl]phenyl}-4-methyl-3-[(1-methyl-1H-imidazol-5-yl)ethynyl]benzamide,

1-methyl-5-({2-methyl-5-[({4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}carbonyl)amino]phenyl}ethynyl)-1H-imidazole-2-carboxamide, and

5-[(5-{[4-{[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl}-3-(trifluoromethyl)phenyl]carbamoyl}-2-methylphenyl)ethynyl]-1-methyl-1H-imidazole-2-carboxamide,

or a pharmaceutically acceptable salt thereof.

22. The compound 1-Methyl-5-(2-methyl-5-[4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenylcarbamoyl]-phenylethynyl)-1H-imidazole-2-carboxylic acid amide or a pharmaceutically acceptable salt thereof.

23. The compound 1-Methyl-5-(2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenylcarbamoyl]-phenylethynyl)-1H-imidazole-2-carboxylic acid amide or a pharmaceutically acceptable salt thereof.

24. The compound 5-[5-(3-Imidazol-1-yl-5-trifluoromethylphenylcarbamoyl)-2-methyl-phenylethynyl]-1-methyl-1H-imidazole-2-carboxylic acid amide or a pharmaceutically acceptable salt thereof.

25. The compound N-{3-chloro-4-[(4-methylpiperazin-1-yl)methyl]phenyl}-4-methyl-3-[(1-methyl-1H-imidazol-5-yl)ethynyl]benzamide or a pharmaceutically acceptable salt thereof.

26. The compound 1-methyl-5-({2-methyl-5-[({4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}carbonyl)amino]phenyl}ethynyl)-1H-imidazole-2-carboxamide or a pharmaceutically acceptable salt thereof.

27. The compound 5-[(5-{[4-{[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl}-3-(trifluoromethyl)phenyl]carbamoyl}-2-methylphenyl)ethynyl]-1-methyl-1H-imidazole-2-carboxamide or a pharmaceutically acceptable salt thereof.

28. A composition comprising a compound of any of claim 1 , 2 , 8 , 3 , 5 , 6 , 7 , 9 , 10 , 11 , 14 , 12 , 13 , 16 or 17 , 18 , 19 , 4 , 15 , 20 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.