Aromatic compounds and poly(oxyalkylene) containing aromatic compounds possessing antibacterial, antifungal or antitumor activity

1. A compound of Formula (I):

wherein:

Z 1 and Z 2 are independently —N(R 3 )—;

R 1 and R 2 are independently substituted alkyl groups of the following structure:

wherein R 15 is hydrogen, hydroxyl, alkoxy, alkyl, cycloalkyl, R 16 is hydrogen, hydroxyl, alkoxy, alkyl or cycloalkyl, or R 15 and R 16 together with the atoms to which they are attached form a heterocyclic ring;

R 3 is hydrogen, or alkyl;

X 2 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkenyl, alkynyl, cycloalkyl or heterocyclic;

X 1 and X 3 are independently aryl, substituted aryl, heteroaryl, substituted heteroaryl, or —CHR 4 , wherein R 4 is natural or unnatural amino acid side chain;

or a pharmaceutically acceptable acid addition salt thereof.

2. The compound of claim 1 , wherein Z 1 and Z 2 are —NH—.

3. The compound of claim 2 , wherein X 2 is aryl, substituted aryl, heteroaryl or substituted heteroaryl.

4. The compound of claim 3 , wherein X 2 is an aryl, substituted aryl, heteroaryl or substituted heteroaryl moiety selected from a group consisting of the following moieties:

wherein,

R 5 is hydrogen, alkyl or substituted alkyl;

R 6 is hydrogen, alkyl, halo or alkoxy;

R 7 is hydrogen, alkyl or halo;

R 8 is hydrogen, alkyl, substituted alkyl, alkoxy or halo;

R 9 is hydrogen, alkyl, substituted alkyl, alkoxy, nitro or halo;

R 10 is hydrogen or alkyl;

R 11 is hydrogen or alkyl; and,

R 12 is hydrogen or alkyl.

5. The compound of claim 2 , wherein X 1 and X 3 are heteroaryl or substituted heteroaryl moieties independently selected from a group consisting of the following moieties:

wherein

R 6 is hydrogen, alkyl, halo or alkoxy;

R 13 is hydrogen or alkyl; and,

R 14 is hydrogen, alkyl or substituted alkyl.

6. The compound of claim 5 , wherein R 14 is an alkyl or substituted alkyl moiety selected from a group consisting of:

7. The compound of claim 4 , wherein X 1 and X 3 are heteroaryl or substituted heteroaryl moieties independently selected from a group consisting of the following moieties:

wherein

R 13 is hydrogen or alkyl;

R 14 is hydrogen, alkyl or substituted alkyl.

8. The compound of claim 7 , wherein X 1 and X 3 are both

wherein R 14 is hydrogen, alkyl or substituted alkyl.

9. The compound of claim 8 , wherein R 14 is an alkyl or substituted alkyl moiety selected from a group consisting of:

10. The compound of claim 1 , wherein the compound is selected from a group consisting of:

N,N′-Bis-[5-(carbamimidoylmethylcarbamoyl)-1-cyclopropylmethyl-1H-pyrrol-3-yl]-terephthalamide;

N,N′-Bis-{1-cyclopropylmethyl-5-[(N-ethylcarbamimidoylmethyl)-carbamoyl]-1H-pyrrol-3 -yl}-terephthalamide;

2,5-Dihydro-thiophene-2,5-dicarboxylic acid bis-{[5-(carbamimidoylmethyl-carbamoyl)-1-cyclopropylmethyl-1H-pyrrol-3-yl]-amide};

N,N′-Bis-[1-butyl-5-(carbamimidoylmethyl-carbamoyl)-1H-pyrrol-3-yl]terephthalamide;

Pyridine-2,5-dicarboxylic acid bis({1-butyl-5-[N-methylcarbamimidoylmethyl)-carbamoyl]-1H-pyrrol-3-yl}-amide);

N,N′-Bis-[1-butyl-5-(methylcarbamimidoylmethyl-carbamoyl)-1H-pyrrol-3-yl]terephthalamide;

N,N′-Bis-[1-butyl-5-(ethylcarbamimidoylmethyl-carbamoyl)-1H-pyrrol-3-yl]terephthalamide;

N,N′-Bis-{1-cyclopropylmethyl-5-[(4,5-dihydro-1H-imidazol-2-ylmethyl)-carbamoyl]-1H-pyrrol-3-yl}-terephthalamide;

Pyridine-2,5-dicarboxylic acid bis{[5-(carbamimidoylmethyl-carbamoyl)-1-cyclopropylmethyl-1H-pyrrol-3-yl]-amide};

Pyrazine-2,5-dicarboxylic acid bis{[5-(carbamimidoylmethyl-carbamoyl)-1-cyclopropylmethyl-1H-pyrrol-3-yl]-amide};

Cyclohexa-1,3-diene-1,4-dicarboxylic acid bis-{[5-(carbamimidoylmethyl-carbamoyl)-1-cyclopropylmethyl-1H-pyrrol-3-yl]-amide}; and

1H-Pyrazole-3,5-dicarboxylic acid bis-{[5-(carbamimidoylmethyl-carbamoyl)-1-cyclopropylmethyl-1H-pyrrol-3-yl]-amide}.

11. A compound of Formula (I):

wherein:

Z 1 and Z 2 are independently —N(R 3 )—;

R 1 and R 2 are independently substituted alkyl, substituted aryl, heteroaryl, substituted heteroaryl, or —(W—) s -(-alk-O—) q —R, where W is selected from the group consisting of alkylene, substituted alkylene, aryl, substituted aryl, heteroaryl, and substituted heteroaryl, s is 0 or 1, R is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclicalkyl, where alk is selected from the group consisting of alkylene and substituted alkylene and q is an integer from 1 to 20, provided that at least one of R 1 and R 2 is a group that can form a pharmaceutically acceptable acid addition salt;

each R 3 is independently hydrogen, alkyl, —(W—) s -(-alk-O—) q —R, or R 3 and R 1 together or R 3 and R 2 together with the atoms to which they are attached form a heterocyclic ring;

X 2 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkenyl, alkynyl, cycloalkyl or heterocyclic;

X 1 and X 3 are independently aryl, substituted aryl, heteroaryl, substituted heteroaryl, or —CHR 4 , wherein R 4 is natural or unnatural amino acid side chain;

or a pharmaceutically acceptable acid addition salt thereof, and further provided that at least one of R 1 and R 2 is —(W—) s -(-alk-O—) q —R.

12. The compound of claim 11 , wherein R 3 is —(W—) s -(-alk-O) q —R group.

13. The compound of claim 11 , wherein Z 1 and Z 2 are —NH—.

14. The compound of claim 13 , wherein X 2 is aryl, substituted aryl, heteroaryl or substituted heteroaryl.

15. The compound of claim 13 , wherein one of R 1 and R 2 is a —(W—) s -(-alk-O—) q —R moiety and the other is a substituted alkyl group.

16. The compound of claim 14 , wherein X 2 is an aryl, substituted aryl, heteroaryl or substituted heteroaryl moiety selected from a group consisting of the following moieties:

wherein,

R 5 is hydrogen, alkyl or substituted alkyl;

R 6 is hydrogen, alkyl, halo or alkoxy;

R 7 is hydrogen, alkyl or halo;

R 8 is hydrogen, alkyl, substituted alkyl, alkoxy or halo;

R 9 is hydrogen, alkyl, substituted alkyl, alkoxy, nitro or halo;

R 10 is hydrogen or alkyl;

R 11 is hydrogen or alkyl; and,

R 12 is hydrogen or alkyl.

17. The compound of claim 13 , wherein X 1 and X 3 are heteroaryl or substituted heteroaryl moieties independently selected from a group consisting of the following moieties:

wherein

R 13 is hydrogen or alkyl; and,

R 14 is hydrogen, alkyl or substituted alkyl.

18. The compound of claim 15 , wherein one of R 1 and R 2 is an —(W—) s -(-alk-O—) q —R moiety and the other is a substituted alkyl moiety independently selected from the group consisting of the following moieties:

wherein

R 15 is hydrogen, hydroxyl, alkoxy, alkyl, cycloalkyl or R 15 and R 16 together with the atoms to which they are attached form a heterocyclic ring;

R 16 is hydrogen, hydroxyl, alkyl or cycloalkyl;

R 17 , R 18 , R 19 and R 20 are independently hydrogen or alkyl;

R 21 is hydrogen alkyl, substituted alkyl, cycloalkyl or acyl;

R 22 is hydrogen or alkyl, or R 22 and R 23 together with the atoms to which they are attached form a heterocyclic ring, or R 22 and R 24 together with the atoms to which they are attached form a heterocyclic ring.

R 23 is hydrogen, hydroxyl, alkyl, cycloalkyl or R 23 and R 24 together with the atoms to which they are attached form a heterocyclic ring;

R 24 is hydrogen, hydroxyl or alkyl;

m is 1, 2 or 3;

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

o is 1, 1, 2 or 3.

19. The compound of claim 17 , wherein R 14 is an alkyl or substituted alkyl moiety, and wherein the moiety is selected from a group consisting of the following moieties:

20. The compound of claim 16 , wherein X 1 and X 3 are heteroaryl or substituted heteroaryl moieties independently selected from a group consisting of the following moieties:

wherein

R 13 is hydrogen or alkyl;

R 14 is hydrogen, alkyl or substituted alkyl;

and wherein one of R 1 and R 2 is an —(W—) s -(-alk-O—) q —R moiety and the other is a substituted alkyl moiety selected from a group consisting of:

wherein

R 15 is hydrogen, hydroxyl, alkoxy, alkyl, cycloalkyl or R 15 and R 16 together with the atoms to which they are attached form a heterocyclic ring;

R 16 is hydrogen, hydroxyl, alkyl or cycloalkyl;

R 17 , R 18 , R 19 and R 20 are independently hydrogen or alkyl;

R 21 is hydrogen alkyl, substituted alkyl, cycloalkyl or acyl;

R 22 is hydrogen or alkyl, or R 22 and R 23 together with the atoms to which they are attached form a heterocyclic ring, or R 22 and R 24 together with the atoms to which they are attached form a heterocyclic ring.

R 23 is hydrogen, hydroxyl, alkyl, cycloalkyl or R 23 and R 24 together with the atoms to which they are attached form a heterocyclic ring;

R 24 is hydrogen, hydroxyl or alkyl;

m is 1, 2 or 3;

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

o is 0, 1, 2or3.

21. The compound of claim 20 , wherein X 2 is

wherein,

R 5 is hydrogen, alkyl or substituted alkyl;

R 6 is hydrogen, alkyl, halo or alkoxy; and

R 7 is hydrogen, alkyl or halo.

22. The compound of claim 20 , wherein X 1 and X 3 are both

wherein R 14 is hydrogen, alkyl or substituted alkyl.

23. The compound of claim 21 , wherein one of R 1 and R 2 is an —(W—) s -(-alk-O—) q —R moiety and the other is of the following structure:

wherein

o is zero;

R 17 and R 18 are hydrogen; and,

R 21 is hydrogen, alkyl or acyl.

24. The compound of claim 22 , wherein one of R 1 and R 2 is an —(W—) s -(-alk-O—) q —R moiety and the other is of the following structure:

wherein

R 15 and R 16 are hydrogen; and,

n is 0, 1 or 2.

25. The compound of claim 23 , wherein R 19 and R 20 are hydrogen, and wherein R 21 is an alkyl group selected from a group consisting of methyl, ethyl and propyl, or an acyl moiety of the structure —C(O)C(R 25 )(R 26 )H,

wherein

R 25 is a substituent selected from a group consisting of the following substituents:

or R 25 and R 26 together with the atom to which they are attached form a heterocyclic ring of the following structure:

and wherein R 26 is a substituent selected from a group consisting of the following substituents: —H, —NH 2 and —NHCH 3 .

26. The compound of claim 23 , wherein one of R 1 and R 2 is an —(W—) s -(-alk-O—) q —R moiety and the other is selected from the group consisting of:

wherein

R 19 and R 20 are independently hydrogen or alkyl; and,

R 21 is hydrogen, alkyl or acyl.

27. The compound of claim 24 , wherein R 14 is an alkyl or substituted alkyl moiety, and wherein the moiety is selected from a group consisting of the following moieties:

28. The compound according to claim 25 , wherein the compound is of the following structure:

wherein R 27 is —(W—) s -(-alk-O—) q —R, where R is hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclicalkyl, where alk is selected from the group consisting of C 1-4 alkylene or C 1-4 substituted alkylene and q is an integer from 2 to 10.

29. The compound according to claim 27 , wherein the compound is of the following structure:

wherein R 27 is —(W—) s -(-alk-O—) q —R, where R is hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclicalkyl, where alk is selected from the group consisting of C 1-4 alkylene or C 1-4 substituted alkylene and q is an integer from 2 to 10; R 14 is hydrogen, —CH 2 CH 2 CH(CH 3 ) 2 or —CH 2 (C 3 H 5 ), and wherein X 2 is a moiety selected from a group consisting of the following moieties:

30. The compound according to claim 11 , wherein R 1 and R 2 are independently —(W—) s -(-alk-O—) q —R moieties.

31. The compound according to claim 11 , wherein R 1 and R 2 are independently —(W—) s -(-alk-O—) q —R moieties where q is an integer from 2 to 10 and alk is a C 1-4 alkylene or a C 1-4 substituted alkylene.

32. The compound according to claim 11 , wherein R 1 and R 2 are independently —(W—) s -(-alk-O—) q —R moieties selected from the group consisting of CH 2 O) 4 H, (CH 2 CH 2 O) 2 H, (CH 2 CH 2 O) 4 H, (CH 2 CH 2 O) 7 H, (CH 2 CH 2 O) 9 H and (CH 2 CH 2 CH 2 O) 2 H.

33. A method of treating bacterial or fungal infections, wherein the method comprises administration of a therapeutically effective amount of a compound of claim 1 .

34. A method of treating bacterial or fungal infections, wherein the method comprises administration of a therapeutically effective amount of a compound of claim 11 .

35. A method of inhibiting topoisomerase, wherein the method comprises administration of a therapeutically effective amount of a compound of claim 1 .

36. A method of inhibiting topoisomerase, wherein the method comprises administration of a therapeutically effective amount of a compound of claim 11 .