PYRIDINONE ANALOGS

1 . A compound having formula (1):

and pharmaceutically acceptable salts thereof;

wherein V, X, and Y are absent if attached to a heteroatom other than Nitrogen, and independently H, halo, azido, R 2 , CH 2 R 2 , SR 2 , OR 2 or NR 1 R 2 when attached to C or N; or

wherein V and X, or X and Y may form a carbocyclic ring, heterocyclic ring, aryl or heteroaryl, each of which may be optionally substituted and/or fused with a cyclic ring;

Z 1 , Z 2 and Z 3 are C, N, O or S; wherein at most one of Z 1 , Z 2 and Z 3 is O, and at most one of Z 1 , Z 2 and Z 3 is S, and at most two of Z 1 , Z 2 and Z 3 are C;

Z is O, S, NR 2 , CH 2 or C═O;

W together with N and Z forms an optionally substituted 5- or 6-membered ring that is fused to an optionally substituted aryl or heteroaryl, wherein said aryl or heteroaryl may be monocyclic or fused with a single or multiple ring, and wherein said ring optionally contains a heteroatom;

U is C(O)R 2 , C(O)OR 2 , C(O)NR 1 R 2 , C(O)NR 1 —(CR 1 2 ) n —NR 3 R 4 , SO 3 R 2 , SO 2 NR 1 R 2 or SO 2 NR 1 —(CR 1 2 ) n —NR 3 R 4 ;

wherein in each NR 1 R 2 , R 1 and R 2 together with N may form an optionally substituted ring;

in NR 3 R 4 , R 3 and R 4 together with N may form an optionally substituted ring;

R 1 and R 3 are independently H or C 1-6 alkyl;

each R 2 is H, or a C 1-10 alkyl or C 2-10 alkenyl each optionally substituted with a halogen, one or more non-adjacent heteroatoms selected from N, O and S, a carbocyclic ring, a heterocyclic ring, an aryl or heteroaryl, wherein each ring is optionally substituted; or R 2 is an optionally substituted carbocyclic ring, heterocyclic ring, aryl or heteroaryl; or R 2 is COR 1 or S(O) x —R 1 wherein x is 1-2;

R 4 is H, a C 1-10 alkyl or C 2-10 alkenyl optionally containing one or more non-adjacent heteroatoms selected from N, O and S, and optionally substituted with a carbocyclic or heterocyclic ring; or R 3 and R 4 together with N may form an optionally substituted ring;

each R 5 is a substituent at any position on W; and is H, OR 2 , amino, alkoxy, amido, halogen, cyano or an inorganic substituent; or R 5 is C 1-6 alkyl, C 2-6 alkenyl, —CONHR 1 , each optionally substituted by halo, carbonyl or one or more non-adjacent heteroatoms; or two adjacent R 5 are linked to obtain a 5-6 membered optionally substituted carbocyclic or heterocyclic ring, optionally fused to an additional optionally substituted carbocyclic or heterocyclic ring; and

n is 1-6.

2 . The compound of claim 1 , wherein T forms an optionally substituted 5-membered ring selected from the group consisting of:

3 . The compound of claim 1 , wherein W together with N and Z form an optionally substituted 5- or 6-membered aryl or heteroaryl ring that is fused to an optionally substituted aryl or heteroaryl selected from the group consisting of:

wherein each Q, Q 1 , Q 2 , and Q 3 is independently CH or N;

P is independently O, CH, C═O or NR 1 ;

n and R 5 is as defined above.

4 . The compound of claim 1 , wherein W together with N and Z form a group having the formula selected from the group consisting of

wherein Z is O, S, NR 2 , CH 2 or C═O;

each Z 4 is CR 6 , NR 2 , or C═O;

R 6 is H, or a substituent known in the art, including but not limited to hydroxyl, alkyl, alkoxy, halo, amino, or amido; and

Ring S and M may be saturated or unsaturated.

5 . The compound of claim 1 , wherein W together with N and Z forms a 5- or 6-membered ring that is fused to a phenyl.

6 . The compound of claim 1 , having the general formula (2A) or (2B):

wherein U, V, W, X, Y, Z, Z 1 , Z 2 , Z 3 , R 5 and n are as described in formula (1);

Z 4 is CR 6 , NR 2 , or C═O;

Z and Z 4 may optionally form a double bond.

7 . The compound of claim 1 , having the general formula (3):

wherein U, V, X, Y, Z, Z 1 , Z 2 , Z 3 , R 5 and n are as described in formula 1.

8 . The compound of claim 1 , having the general formula (4A) or (4B):

wherein U, V, X, Z, R 5 and n are as described above.

9 . The compound of claim 1 , wherein U is C(O)NR 1 R 2 ;

R 1 is H, and R 2 is a C 1-10 alkyl optionally substituted with a heteroatom, or an optionally substituted C 3-6 cycloalkyl, aryl or a 5-14 membered heterocyclic ring containing one or more N, O or S.

10 . The compound of claim 9 , where U is C(O)NR 1 R 2 , wherein R 2 is a C 1-10 alkyl substituted with an optionally substituted morpholine, thiomorpholine, imidazole, aminodithiadazole, pyrrolidine, piperazine, pyridine or piperidine ring.

11 . The compound of claim 9 , where U is C(O)NR 1 R 2 , where in R 1 and R 2 together with N form an optionally substituted piperidine, pyrrolidine, piperazine, morpholine, thiomorpholine, imidazole, or aminodiathiazole.

12 . The compound of claim 1 , wherein U is C(O)NR 1 —(CR 1 2 ) n —NR 3 R 4 ; n is 1-4; and R 3 and R 4 in NR 3 R 4 together form an optionally substituted piperidine, pyrrolidine, piperazine, morpholine, thiomorpholine, imidazole, or aminodiathiazole.

13 . The compound of claim 1 , wherein U is C(O)NH—(CH 2 ) n —NR 3 R 4 ; and R 3 and R 4 together with N form an optionally substituted pyrrolidine, which may be linked to (CH 2 ) n at any position in the pyrrolidine ring.

14 . The compound of claim 13 , wherein R 3 and R 4 together with N form an N-methyl substituted pyrrolidine.

15 . The compound of claim 14 , wherein U is C(O)NH—(CH 2 ) 2 -(1-methylpyrrolidin-2-yl) or C(O)NH—(CH 2 ) 2 -(2-pyrrolidin-1-yl).

16 . The compound of claim 1 , wherein Z is S or NR 2 .

17 . The compound of claim 1 , wherein at least one of V, X or Y when attached to C is halo.

18 . The compound of claim 1 , wherein each optionally substituted moiety may be substituted with one or more acetyl, OR 2 , amino, alkoxy, amido, halogen, cyano, an inorganic substituent; or a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, —CONHR 1 , each optionally substituted by halo, an oxo group, aryl or one or more heteroatoms; inorganic substituents, aryl, carbocyclic or a heterocyclic ring.

19 . The compound of claim 1 , wherein two of Z 1 , Z 2 and Z 3 are C and the other is N, O or S.

20 . The compound of claim 19 , wherein Z 1 is S.

21 . The compound of claim 1 , wherein two of Z 1 , Z 2 and Z 3 are selected from N, O and S, and the other is C.

22 . A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable carrier.

23 . A method for ameliorating a tumor or cancer, comprising administering to a system or a subject in need thereof an effective amount of the compound of claim 1 or a pharmaceutical composition thereof and optionally with a procedure and/or a chemotherapeutic agent, thereby reducing cell proliferation and/or ameliorating said cell-proliferative disorder.

24 . The method of claim 23 , wherein said cell proliferative disorder is a tumor or cancer.

25 . The method of claim 23 , wherein the compound of claim 1 is administered to a subject in need thereof, and said subject is human or an animal.

26 . A method for reducing microbial titers and/or ameliorating a microbial infection, comprising contacting a system or a subject in need thereof with an effective amount of the compound of claim 1 or a pharmaceutical composition thereof and optionally with an antimicrobial agent, thereby reducing microbial titers and/or ameliorating said microbial infection.

27 . The method of claim 26 , where said system is a cell or tissue, and said subject is human or an animal.

28 . The method of claim 26 , wherein the microbial titers and/or microbial infection are viral, bacterial or fungal titers.

29 . A method for inducing cell death and/or inducing apoptosis, comprising administering to a system or a subject in need thereof an effective amount of a composition comprising a compound in claim 1 , or a pharmaceutical composition thereof and optionally with a procedure and/or a chemotherapeutic agent, thereby inducing cell death and/or inducing apoptosis.

30 . The method of claim 29 , wherein said system is a cell or tissue, and said subject is human or an animal.

31 . The method of claim 29 , wherein said procedure is radiotherapy or a surgical procedure.

32 . The compound of claim 1 , selected from the group consisting of

and the pharmaceutically acceptable salts thereof.

34 . A composition comprising a compound of claim 1 in combination with a protein kinase.

35 . A composition comprising a compound of claim 1 in combination with a nucleic acid containing a nucleotide sub-sequence from SEQ ID NO: 1, a complement thereof, or RNA transcript of the foregoing.

36 . The compound of claim 21 , wherein Z 1 is S, Z 2 is C and Z 3 is N.