SUBSTITUTED ACETYLENIC PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS KINASE INHIBITORS

1 . A compound of the Formula I

or a tautomer, or an individual isomer or a mixture of isomers thereof wherein:

Ring T is a 5-membered heteroaryl ring containing 1 or 2 nitrogens with the remaining ring atoms being carbon, substituted on at least two ring atoms with R 1 groups, at least two of which being located on adjacent ring atoms, and, together with the atoms to which they are attached, forming a saturated, partially saturated or unsaturated 5- or 6-membered ring (Ring E), containing 0-3 heteroatoms selected from O, N, and S and being optionally substituted with 1-4 R e groups:

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

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

each occurrence of R a , R b and R t is 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 2 ) 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 each Y is independently a bond, —O—, —S— or —NR 3 —;

R e , at each occurrence, is independently selected from the group consisting of halo, ═O, —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 2 ) 3 , —NR 2 SO 2 R 2l , —S(O) t R 2 , —SO 2 NR 2 R 3 and —NR 2 SO 2 NR 2 R 3 , wherein each Y is independently a bond, —O—, —S— or —NR 3 —;

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

alternatively, R 2 and R 3 , taken together with the atom to which they are attached, form a 5- or 6-membered saturated, partially saturated or unsaturated ring, which can be optionally substituted and which contains 0-2 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 alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocyclic and heteroaryl moieties is optionally substituted;

is 0, 1, 2, 3 or 4;

n is 2 or 3;

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

r is 0, 1 or 2;

or a pharmaceutically acceptable salt, solvate or hydrate thereof.

2 . A compound of claim 1 wherein Ring T has the following structure:

in which Ring E is a 5- or 6-membered unsaturated rind comprising 0-3 heteroatoms selected from O, N, and S, and s is 0, 1, 2, 3 or 4.

3 . A compound according to claim 1 wherein Ring T is a bicyclic heteroaryl ring selected from:

and s is 0, 1, 2, 3 or 4.

4 . A compound of claim of the formula:

wherein:

Ring C is a 5- or 6-membered heterocyclic or heteroaryl ring, comprising carbon atoms and 1-3 heteroatoms independently selected from 0, N and S(O);

R c , at each occurrence, is independently selected from halo, ═O, —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 , —Si(R 2 ) 3 , —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 ), —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 each Y is independently a bond, —O—, —S— or —NR 3 —; and,

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

5 . A compound of claim 4 wherein Ring T has the following structure:

and s is 0, 1, 2, 3 or 4.

6 . A compound of claim 5 wherein Rings A and B are aryl.

7 . A compound of claim 5 or 6 wherein Ring C is an imidazole ring

8 . A compound of claim 7 selected from Formulae IIa, IIb, and IIc:

9 . A compound of claim 8 wherein s is 0; m, p and v are R a and R c are methyl; and R b is CF 3 .

10 . A compound of claim 1 having the formula:

wherein;

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

L 2 is (CH 2 ) x , O(CH 2 ) x , NR 3 (CH 2 ) x , S(CH 2 ) x or (CH 2 ) x NR 3 C(O)(CH 2 ) x in either direction;

R d , at each occurrence, is selected from the group consisting of H, halo, ═O, —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 2 ) 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 each 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, R 2 and R 3 , taken together with the atom to which they are attached, form a 5- or 6-membered saturated, partially saturated or unsaturated ring, which can be optionally substituted and which contains 0-2 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 alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocyclic and heteroaryl moieties in this Section 1 is optionally substituted;

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

x is 0, 1, 2 or 3; and,

z is 1, 2, 3 or 4.

11 . A compound of claim 10 wherein Ring T has the following structure:

and s is 0, 1, 2, 3 or 4.

11 . A compound of claim 11 , wherein Rings A and B are aryl.

13 . A compound of claim 11 or 12 wherein Ring T is a bicyclic heteroaryl ring selected from:

and s is 0, 1, 2, 3 or 4.

14 . A compound of claim 13 , wherein Ring D is a piperazine ring and L 2 is CH 2 .

15 . A compound of claim 14 selected from Formulae IIIa, IIIb, and IIIc:

16 . A compound of claim 15 wherein s is 0, m is 1, p is 1, R a is methyl, R b is CF 3 , and R d is methyl or —CH 2 CH 2 OH.

17 . A method for treating cancer in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of a compound of any of claim 1 - 6 or 10 - 12 or a pharmaceutically acceptable salt, solvate or hydrate thereof.

18 . A method for treating cancer in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of a compound of claim 7 or a pharmaceutically acceptable salt, solvate or hydrate thereof.

19 . A method for treating cancer in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of a compound of claim 13 or a pharmaceutically acceptable salt, solvate or hydrate thereof.

20 . A composition comprising a compound of any of claim 1 - 8 or 10 - 12 or a pharmaceutically acceptable salt, solvate or hydrate thereof and a pharmaceutical acceptable carrier, diluent or vehicle.

21 . A composition comprising a compound of claim 7 or a pharmaceutically acceptable salt, salivate or hydrate thereof and a pharmaceutical acceptable carrier, diluent or vehicle.

22 . A composition comprising a compound of claim 13 or a pharmaceutically acceptable salt, solvate or hydrate thereof and a pharmaceutical acceptable carrier, diluent or vehicle.