Pharmaceutical compounds

1 - 63 . (canceled)

64 . A compound of the formula (I):

or a salt, N-oxide or solvate thereof;

wherein

X is CR 5 or N;

A is a bond or —(CH 2 ) m —(B) n —;

B is C═O, NR g (C═O) or O(C═O) wherein R g is hydrogen or C 1-4 hydrocarbyl optionally substituted by hydroxy or C 1-4 alkoxy;

m is 0, 1 or 2;

n is O or 1;

R 1 is hydrogen, a carbocyclic or heterocyclic group having from 3 to 12 ring members, or an optionally substituted C 1-8 hydrocarbyl group;

R 2 is hydrogen, halogen, methoxy, or a C 1-4 hydrocarbyl group optionally substituted by halogen, hydroxyl or methoxy;

R 3 and R 4 are the same or different and each is selected from hydrogen, CN, C(O)R 8 , optionally substituted C 1-8 hydrocarbyl and carbocyclic or heterocyclic groups having from 3 to 12 ring members; and

R 5 is hydrogen, a group R 2 or a group R 10 wherein R 10 is selected from halogen, hydroxy, trifluoromethyl, cyano, nitro, carboxy, amino, mono- or di-C 1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members; a group R a —R b wherein R a is a bond, O, CO, X 1 C(X 2 ), C(X 2 )X 1 , X 1 C(X 2 )X 1 , S, SO, SO 2 , NR c , SO 2 NR c or NR c SO 2 ; and R b is selected from hydrogen, carbocyclic and heterocyclic groups having from 3 to 12 ring members, and a C 1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, carboxy, amino, mono- or di-C 1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members and wherein one or more carbon atoms of the C 1-8 hydrocarbyl group may optionally be replaced by O, S, SO, SO 2 , NR c , X 1 C(X 2 ), C(X 2 )X 1 or X 1 C(X 2 )X 1 ;

R c is selected from hydrogen and C 1-4 hydrocarbyl;

X 1 is O, S or NR c and X 2 is ═O, ═S or ═NR c ; and

R 8 is selected from OR 11 , SR 11 and NR 12 R 13 ;

R 11 is selected from optionally substituted C 1-8 hydrocarbyl and carbocyclic or heterocyclic groups having from 3 to 12 ring members; and

one of R 12 and R 13 is a group R 11 and the other of R 12 and R 13 is hydrogen or C 1-4 alkyl; or R 12 and R 13 and the nitrogen atom to which they are attached together form a saturated heterocyclic group having from 4 to 7 ring members and containing 1, 2 or 3 heteroatom ring members selected from N, O and S.

65 . A compound according to claim 64 wherein X is N.

66 . A compound according to claim 64 wherein m is 0 or 1, n is 1 and B is C═O.

67 . A compound according to claim 64 wherein R 2 is hydrogen, fluorine or methyl, preferably hydrogen.

68 . A compound according to claim 64 wherein R 1 is a monocyclic or bicyclic aryl or heteroaryl group of 3 to 12 ring members which is unsubstituted or substituted by one or more substituent groups R 10 as defined in claim 64 .

69 . A compound according to claim 68 wherein the aryl or heteroaryl group R 1 is selected from phenyl, pyrazolo[1,5-a]pyridinyl, furanyl, indolyl, oxazolyl, thiazolyl, isoxazolyl, pyrrolyl, pyridyl, quinolinyl, 2,3-dihydro-benzo[1,4]dioxine, benzo[1,3]dioxole, 2,3-dihydrobenzofuranyl, imidazolyl and thienyl; each optionally substituted by one or more substituent groups R 10 as defined in claim 64 .

70 . A compound according to claim 69 wherein the aryl or heteroaryl group R 1 is unsubstituted or is substituted by one or more substituent groups selected from the group R 10a consisting of halogen, hydroxy, trifluoromethyl, cyano, nitro, carboxy, heterocyclic groups having 5 or 6 ring members and up to 2 heteroatoms selected from O, N and S, a group R a —R b wherein R a is a bond, O, CO, X 3 C(X 4 ), C(X 4 )X 3 , X 3 C(X 4 )X 3 , S, SO, or SO 2 , and R b is selected from hydrogen, heterocyclic groups having 5 or 6 ring members and up to 2 heteroatoms selected from O, N and S, and a C 1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, carboxy, amino, mono- or di-C 1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having 5 or 6 ring members and up to 2 heteroatoms selected from O, N and S; wherein one or more carbon atoms of the C 1-8 hydrocarbyl group may optionally be replaced by O, S, SO, SO 2 , X 3 C(X 4 ), C(X 4 )X 3 or X 3 C(X 4 )X 3 ; X 3 is O or S; and X 4 is ═O or ═S.

71 . A compound according to claim 64 wherein R 1 is a group as set out in Table 1:

TABLE 1

A1

A2

A3

A4

A5

A6

A7

A8

A9

A10

A11

A12

A13

A14

A15

A16

A17

A18

A19

A20

A21

A22

A23

A24

A25

A26

A27

A28

A29

A30

A31

A32

A33

A34

A35

A36

A37

A38

A39

A40

A41

A42

A43

A44

A45

A46

A47

A48

A49

A50

A51

A52

A53

A54

A55

A56

A57

A58

A59

A60

A61

A62

A63

72 . A compound according to claim 71 wherein R 1 is selected from groups A1, A3, A61, A62 and A63 in Table 1 of claim 71 (and more preferably A1).

73 . A compound according to claim 64 wherein:

(A) one or both of R 3 and R 4 is or are other than hydrogen and is or are selected from optionally substituted C 1-8 hydrocarbyl and an optionally substituted carbocyclic or heterocyclic group selected from phenyl, naphthyl, thienyl, isoxazolyl, pyridyl, 2,3-dihydro-benzo[1,4]dioxine; or

(B) one of R 3 and R 4 is an optionally substituted group selected from phenyl, naphthyl, thienyl, isoxazolyl, pyridyl, 2,3-dihydro-benzo[1,4]dioxine, and the other one of R 3 and R 4 is an optionally substituted C 1-8 hydrocarbyl group;

wherein the optional substituents in (A) and (B) for the carbocyclic or heterocyclic groups are selected from the groups R 10 and R 10a as defined in claim 64 or claim 70; and

wherein the optionally substituted C 1-8 hydrocarbyl group (A) and (B) is selected from:

(i) C 1-4 alkyl, hydroxy-C 1-4 alkyl and C 2-4 alkenyl; and

(ii) a C 1-8 hydrocarbyl group optionally substituted by a substituent selected from optionally substituted monocyclic carbocyclic and heterocyclic groups, NR 12 R 13 , C 1-4 alkoxy, halogen, hydroxy, C 1-4 alkylsulphonylamino, amino, mono- and di-C 1-4 alkylamino, wherein the alkyl residues of the C 1-4 alkoxy, mono- and di-C 1-4 alkylamino groups may themselves be further substituted by a substituent selected from NR 12 R 13 , C 1-4 alkoxy, hydroxy, C 1-4 alkylsulphonylamino, amino, and mono- and di-C 1-4 alkylamino, wherein R 12 and R 13 are as defined in claim 64 , and wherein the optional substituents for the carbocyclic and heterocyclic groups are selected from the group R 10 as defined in any one of the preceding claims; or

(C) one of R 3 and R 4 is a group C(O)NR 12 R 13 wherein R 12 and R 13 and the nitrogen atom to which they are attached together form a saturated heterocyclic group having from 4 to 7 ring members and containing 1, 2 or 3 heteroatom ring members selected from N, O and S; or

(D) R 3 and R 4 are the same or different and are selected from C 1-4 alkyl groups optionally substituted by halogen, hydroxy or methoxy.

74 . A compound according to claim 64 wherein the imidazole group

is selected from the groups B1 to B40 set out in Table 2:

TABLE 2

Examples of the Imidazole Group

B1

B2

B3

B4

B5

B6

B7

B8

B9

B10

B11

B12

B13

B14

B15

B16

B17

B18

B19

B20

B21

B22

B23

B24

B25

B26

B27

B28

B29

B30

B31

B32

B33

B34

B35

B36

B37

B38

B39

B40

B41

75 . A compound according to claim 74 wherein the imidazole group is (i) selected from the groups B1 to B6, B8, B9 and B11 to B16 of Table 2, or is (ii) selected from B18, B19, B20, B22, B24, B25, B26, B27, B28, B29, B31, B34, B35, B37 and B38; or is (iii) selected from the groups B1 to B6, B8, B9, B11 to B13, B15 and B16; or is (iv) selected from the groups B2, B4, B12, B15 and B16.

76 . A compound according to claim 64 in the form of a salt or solvate.

77 . A pharmaceutical composition comprising a compound of the formula (I) as defined in claim 64 and a pharmaceutically acceptable carrier.

78 . A method for the prophylaxis or treatment of a disease state or condition mediated by a cyclin dependent kinase, which method comprises administering to a subject in need thereof a compound of the formula (I) as defined in claim 64 .

79 . A method according to claim 78 wherein the disease state or condition is selected from proliferative disorders, viral infections, autoimmune diseases and neurodegenerative diseases.

80 . A method according to claim 79 wherein the proliferative disorder is a cancer selected from breast cancer, ovarian cancer, colon cancer, prostate cancer, oesophageal cancer, squamous cancer, and non-small cell lung carcinomas.

81 . A method of modulating a cellular process by inhibiting the activity of a cyclin dependent kinase using a compound of the formula (I) as defined in claim 64 .

82 . A method for treating a disease or condition comprising or arising from abnormal cell growth in a mammal, which method comprises administering to the mammal a compound of formula (I) as defined in claim 64 in an amount effective to inhibit abnormal cell growth.

83 . A method for the prophylaxis or treatment of a disease state or condition mediated by glycogen synthase kinase-3, which method comprises administering to a subject in need thereof a compound of the formula (I) as defined in claim 64.