Acetylenic heteroaryl compounds

1. A compound of the Formula I, a tautomer thereof, or a pharmaceutically acceptable salt thereof:

wherein:

Ring T represents a substituted or unsubstituted 6-membered heteroaryl ring, comprising 2 nitrogens;

Ring A represents a 5- or 6-membered aryl or heteroaryl ring and is optionally substituted with 1-4 R a groups;

Ring B represents a 5- or 6-membered aryl or heteroaryl ring and is optionally substituted with 1-5 R b groups;

L 1 is selected from NR 1 C(O) and C(O)NR 1 ;

at each occurrence, R a and R b are independently selected from the group consisting of 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 , —S— or —NR 3 —;

R 1 , R 2 and R 3 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocyclyl and heteroaryl;

wherein the —NR 2 R 3 moiety is optionally a 5- or 6-membered saturated, partially saturated or unsaturated ring, which is 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, heterocyclyl, heteroaryl;

(a) X 1 is CH or CR t1 wherein R t1 is halo, OR 5 , alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, carbon linked heteroaryl, carbon linked heterocyclyl; wherein R 5 is H, alkyl, alkenyl alkynyl;

X 2 is N; and

X 3 is CR t4 ; wherein R t4 is H, halo, —CN, —NO 2 , —R 2 , —OR 2 , —C(O)YR 2 , —OC(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 2 )(YR 2 ), —Si(R 4 ) 3 , —S(O) r R 2 , —SO 2 NR 2 R 3 ;

or,

(b) X 1 is CR t , X 2 is N and X 3 is CR t3 , wherein R t is selected from —CN, —NO 2 , —OR 6 , —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 R 6 is cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, or heterocyclyl and wherein R t3 is selected from H or R a ;

(b)-1: at least one of R t , R t3 , R a and R b is or contains a YP(═O)(YR 4 )(YR 4 ), a Si(R 4 ) 3 or —YC(═NR 3 )YR 2 substituent; or

(b)-2: at least one of R a and R t is or contains a —NR 2 C(═S)OR 2 , —OC(═S)YR 2 , or —C(═S)OR 2 substituent; or

(b)-3: at least one of R b and R t3 is or contains a —NR 2 C(═S)YR 2 , —OC(═S)YR 2 , or —C(═S)YR 2 substituent;

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

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

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

r is 0, 1 or 2.

2. A compound of claim 1 wherein:

X 1 is CH or CR t1 ;

X 2 is N;

X 3 is CR t4 .

3. A compound of any of claim 1 or 2 having Formula III:

wherein:

Ring C represents a 5- or 6-membered heterocyclic or heteroaryl ring, comprising carbon atoms and 1-3 heteroatoms selected from O, N and S(O) r and is optionally substituted on carbon or heteroatom(s);

R c , at each occurrence, is independently 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;

wherein the —NR 2 R 3 moiety is optionally a 5- or 6-membered saturated, partially saturated or unsaturated ring, which is 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;

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

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

4. A compound of claim 3 wherein Ring C is a substituted or unsubstituted heteroaryl ring.

5. A compound of claim 4 wherein Ring C is a substituted or unsubstituted imidazole ring.

6. A compound of claim 5 selected from the following formulae:

7. A compound of any of claim 1 or 2 having Formula IV:

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 and is optionally substituted with 1-5 R d groups;

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;

wherein the —NR 2 R 3 moiety is optionally a 5- or 6-membered saturated, partially saturated or unsaturated ring, which is 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 selected from 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.

8. A compound of claim 7 wherein Ring D is a substituted or unsubstituted heteroaryl.

9. A compound of claim 7 wherein Ring D is a substituted or unsubstituted piperazine ring and L 2 is CH 2 .

10. A compound of claim 9 selected from the following formulae:

11. A composition comprising a compound of any of claim 1 or 2 ; or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, diluent or vehicle.

12. A composition comprising a compound of claim 3 ; or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, diluent or vehicle.

13. A composition comprising a compound of claim 7 ; or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, diluent or vehicle.

14. A compound selected from the group consisting of:

4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-3-(pyrimidin-5-ylethynyl)benzamide;

3-{[2-(2-amino-2-oxoethyl)pyrimidin-5-yl]ethynyl}-4-methyl-N-[4-(trifluoromethyl)pyridin-2-yl]benzamide; and

N-[4-{[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl}-3-(trifluoromethyl)phenyl]-4-methyl-3-(pyrimidin-5-ylethynyl)benzamide,

or a pharmaceutically acceptable salt thereof.

15. A composition comprising a compound selected from the group consisting of:

4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-3-(pyrimidin-5-ylethynyl)benzamide;

3-{[2-(2-amino-2-oxoethyl)pyrimidin-5-yl]ethynyl}-4-methyl-N-[4-(trifluoromethyl)pyridin-2-yl]benzamide; and

N-[4-{[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl}-3-(trifluoromethyl)phenyl]-4-methyl-3-(pyrimidin-5-ylethynyl)benzamide,

or a pharmaceutically acceptable salt thereof,

and a pharmaceutically acceptable carrier, diluent or vehicle.

16. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

17. A composition comprising compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof,

and a pharmaceutically acceptable carrier, diluent or vehicle.