Anti-cancer and anti-microbial 5-membered heterocyclic compounds

1. A compound having the structure of formula I:

and pharmaceutically acceptable salts or prodrugs thereof, wherein:

R 1 is a molecular fragment having the structure of formula (II),

Z is selected from the group consisting of O, S, and NR 5 ;

R 6 and R 7 are separately selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; aryl; heteroaryl; heterocycloalkyl; ester; arylalkoxy carbonyl; alkoxy carbonylacyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; phenyl; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; cyano; and halogenated alkyl including polyhalogenated alkyl;

R 8 and R 9 are separately selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; aryl; heteroaryl; heterocycloalkyl; ester; arylalkoxy carbonyl; alkoxy carbonylacyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; phenyl; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; and halogenated alkyl including polyhalogenated alkyl; or are separately absent;

R 10 and R 11 are separately selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; aryl; heteroaryl; heterocycloalkyl; ester; arylalkoxy carbonyl; alkoxy carbonylacyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; phenyl; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; cyano; and halogenated alkyl including polyhalogenated alkyl; or are separately absent;

R 2 is selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; heteroaryl; ester; arylalkoxy carbonyl; alkoxy carbonylacyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; cyano; and halogenated alkyl including polyhalogenated alkyl;

R 3 is ═O;

R 1′ is selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; aryl; heteroaryl; heterocycloalkyl; ester; arylalkoxy carbonyl; alkoxy carbonylacyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; phenyl; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; cyano; and halogenated alkyl including polyhalogenated alkyl; or are separately absent;

R 2′ is selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; heteroaryl; ester; arylalkoxy carbonyl; alkoxy carbonylacyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; cyano; and halogenated alkyl including polyhalogenated alkyl; or are separately absent;

Y is separately selected from the group consisting of O, S, and NR 5 ;

R 4 and each R 5 are separately selected from the group consisting of hydrogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues: C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2-6 heteroalkyl, C 2-6 aminoalkyl, C 2-6 haloalkyl, C 1-6 alkoxycarbonyl, and C 2-6 hydroxyalkyl; C 3-8 cycloalkyl; —C(O)—C 5-6 aryl substituted with C 1-3 alkyl or halo; C 5-6 aryl; C 5-6 heteroaryl; C 5-6 cycloalkyl; and C 5-6 heterocycloalkyl, or are separately absent;

any bond represented by a dashed and solid line represents a bond selected from the group consisting of a single bond and a double bond;

any bond represented by a single dashed line is a single bond or is absent; and

any carbon-carbon double bond has a configuration selected from the group consisting of cis and trans.

2. The compound of claim 1 , wherein Y is O.

3. The compound of claim 1 , wherein Z is O.

4. The compound of claim 1 , wherein R 4 is H.

5. The compound of claim 1 , wherein R 4 is absent.

6. The compound of claim 1 , wherein R 8 , R 9 , R 10 , and R 11 are separately hydrogen or absent.

7. The compound of claim 1 , wherein R 2 is a mono-substituted, poly-substituted, or unsubstituted variant of C 1 -C 24 alkyl.

8. The compound of claim 1 , wherein R 6 and R 7 are separately mono-substituted, poly-substituted, or unsubstituted variants of C 1 -C 24 alkyl.

9. The compound of claim 1 , having the structure of formula VI, wherein the crossed double bond indicates that the double bond may have either trans or cis geometry:

10. The compound of claim 1 , having the structure of formula VII, wherein the crossed double bond indicates that the double bond may have either trans or cis geometry:

11. The compound of claim 1 , having the structure of formula VIII, wherein the crossed double bond indicates that the double bond may have either trans or cis geometry:

12. A compound having the structure of formula III:

and pharmaceutically acceptable salts or prodrugs thereof, wherein:

Y is selected from the group consisting of O, S, and NR 5 ;

R 2 , R 6 , and R 7 are separately selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; aryl; heteroaryl; heterocycloalkyl; ester; arylalkoxy carbonyl; alkoxy carbonylacyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; phenyl; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; cyano; and halogenated alkyl including polyhalogenated alkyl;

R 2′ is selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; aryl; heteroaryl; heterocycloalkyl; ester; arylalkoxy carbonyl; alkoxy carbonylacyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; phenyl; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; cyano; and halogenated alkyl including polyhalogenated alkyl; or is absent;

R 4 and R 5 are separately selected from the group consisting of hydrogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups: C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2-6 heteroalkyl, C 2-6 aminoalkyl, C 2-6 haloalkyl, C 1-6 alkoxycarbonyl, and C 2-6 hydroxyalkyl; C 3-8 cycloalkyl; —C(O)—C 5-6 aryl substituted with C 1-3 alkyl or halo; C 5-6 aryl; C 5-6 heteroaryl; C 5-6 cycloalkyl; and C 5-6 heterocycloalkyl or are separately absent;

R 8 , R 9 , R 10 , and R 11 are separately selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; aryl; heteroaryl; heterocycloalkyl; ester; arylalkoxy carbonyl; alkoxy carbonylacyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; phenyl; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; cyano; and halogenated alkyl including polyhalogenated alkyl; or are separately absent;

any bond represented by a dashed and solid line represents a bond selected from the group consisting of a single bond and a double bond;

any bond represented by a single dashed line is a single bond or is absent; and

any carbon-carbon double bond has a configuration selected from the group consisting of cis and trans.

13. The compound of claim 12 , wherein Y is O.

14. The compound of claim 12 , wherein R 2 is a mono-substituted, poly-substituted, or unsubstituted variant of C 1 -C 24 alkyl.

15. The compound of claim 12 , wherein R 6 and R 7 are separately mono-substituted, poly-substituted, or unsubstituted variants of straight chain C 1 -C 24 alkyl.

16. The compound of claim 12 , wherein R 4 is H.

17. The compound of claim 12 , wherein R 4 is absent.

18. The compound of claim 12 , wherein R 2 ′ is H.

19. The compound of claim 12 , wherein R 2 ′ is absent.

20. The compound of claim 12 , wherein R 8 , R 9 , R 10 , and R 11 are separately hydrogen or absent.

21. The compound of claim 12 , having the structure of formula VI, wherein the crossed double bond indicates that the double bond may be of cis or trans geometry:

22. The compound of claim 12 , having the structure of formula VII, wherein the crossed double bond indicates that the double bond may be of either cis or trans geometry:

23. The compound of claim 12 , having the structure of formula VIII, wherein the crossed double bond indicates that the double bond may have either trans or cis geometry:

24. A compound having the structure of formula IV:

and pharmaceutically acceptable salts or prodrugs thereof, wherein:

R 2 , R 6 , and R 7 are separately selected from the group consisting of mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl;

R 2′ is selected from the group consisting of hydrogen and mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl;

R 4 is selected from the group consisting of hydrogen, straight- or branched-chain C 1-6 alkyl, straight- or branched-chain C 2-6 alkenyl, and straight- or branched-chain C 2-6 alkynyl, or is absent;

any bond represented by a dashed and solid line represents a bond selected from the group consisting of a single bond and a double bond with the proviso that such bonds in the compound of formula IV may not both be double bonds; and

any carbon-carbon double bond has a configuration selected from the group consisting of cis and trans.

25. The compound of claim 24 , having the structure of formula VI, wherein the crossed double bond indicates that the double bond may be of either cis or trans geometry:

26. The compound of claim 24 , having the structure of formula VII, wherein the crossed double bond indicates that the double bond may be of either cis or trans geometry:

27. The compound of claim 26 , having the structure of formula VIII, wherein the crossed double bond indicates that the double bond may have either trans or cis geometry:

28. A compound having the structure of formula V:

and pharmaceutically acceptable salts or prodrugs thereof, wherein:

Y is selected from the group consisting of O and NR 5 ;

Z is selected from the group consisting of O, S, and NR 5 ;

R 2 , R 6 , and R 7 are separately selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; aryl; heteroaryl; heterocycloalkyl; ester; arylalkoxy carbonyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; phenyl; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; cyano; and halogenated alkyl including polyhalogenated alkyl;

R 2′ is selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; aryl; heteroaryl; heterocycloalkyl; ester; arylalkoxy carbonyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; phenyl; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; cyano; and halogenated alkyl including polyhalogenated alkyl; or is absent;

R 4 and each R 5 are separately selected from the group consisting of hydrogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups: C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2-6 heteroalkyl, C 2-6 aminoalkyl, C 2-6 haloalkyl, C 1-6 alkoxycarbonyl, and C 2-6 hydroxyalkyl; C 3-8 cycloalkyl; —C(O)—C 5-6 aryl substituted with C 1-3 alkyl or halo; C 5-6 aryl; C 5-6 heteroaryl; C 5-6 cycloalkyl; and C 5-6 heterocycloalkyl or are separately absent;

R 8 and R 9 are separately selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; aryl; heteroaryl; heterocycloalkyl; ester; arylalkoxy carbonyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; phenyl; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; and halogenated alkyl including polyhalogenated alkyl; or are separately absent;

R 10 and R 11 are separately selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 1 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; aryl; heteroaryl; heterocycloalkyl; ester; arylalkoxy carbonyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; phenyl; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; cyano; and halogenated alkyl including polyhalogenated alkyl; or are separately absent;

any bond represented by a dashed and solid line represents a bond selected from the group consisting of a single bond and a double bond;

any bond represented by a single dashed line is a single bond or is absent; and any carbon-carbon double bond has a configuration selected from the group consisting of cis and trans.

29. The compound of claim 28 , having the structure of formula VI, wherein the crossed double bond indicates that the double bond may be of either cis or trans geometry:

30. The compound of claim 28 , having the structure of formula VII, wherein the crossed double bond indicates that the double bond may be of either cis or trans geometry:

31. The compound of claim 28 , having the structure of formula VIII, wherein the crossed double bond indicates that the double bond may have either trans or cis geometry:

32. A compound having the structure of formula V:

and pharmaceutically acceptable salts or prodrugs thereof, wherein:

Y is selected from the group consisting of O, S, and NR 5 ;

Z is selected from the group consisting of O, S, and NR 5 ;

R 2 , R 6 , and R 7 are separately selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; aryl; heteroaryl; heterocycloalkyl; ester; arylalkoxy carbonyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; phenyl; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; cyano; and halogenated alkyl including polyhalogenated alkyl;

R 2′ is selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; aryl; heteroaryl; heterocycloalkyl; ester; arylalkoxy carbonyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; phenyl; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; cyano; and halogenated alkyl including polyhalogenated alkyl; or is absent;

R 4 and each R 5 are separately selected from the group consisting of hydrogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups: C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2-6 heteroalkyl, C 2-6 aminoalkyl, C 2-6 haloalkyl, C 1-6 alkoxycarbonyl, and C 2-6 hydroxyalkyl; C 3-8 cycloalkyl; —C(O)—C 5-6 aryl substituted with C 1-3 alkyl or halo; C 5-6 aryl; C 5-6 heteroaryl; C 5-6 cycloalkyl; and C 5-6 heterocycloalkyl or are separately absent;

R 8 and R 9 are separately selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl; cycloalkenyl; alkoxy; cycloalkoxy; aryl; heteroaryl; heterocycloalkyl; ester; arylalkoxy carbonyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; phenyl; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; and halogenated alkyl including polyhalogenated alkyl; or are separately absent;

R 10 and R 11 are separately selected from the group consisting of hydrogen; halogen; mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, or C 2 -C 24 alkynyl; acyl; acyloxy; alkyloxycarbonyloxy; aryloxycarbonyloxy; cycloalkyl cycloalkenyl alkoxy; cycloalkoxy; aryl; heteroaryl; heterocycloalkyl; ester; arylalkoxy carbonyl; amino; aminocarbonyl; amide; aminocarbonyloxy; nitro; azido; phenyl; hydroxy; alkylthio; arylthio; oxysulfonyl; carboxy; cyano; and halogenated alkyl including polyhalogenated alkyl; or are separately absent;

any bond represented by a dashed and solid line represents a bond selected from the group consisting of a single bond and a double bond;

any bond represented by a single dashed line is a single bond or is absent; and any carbon-carbon double bond has a configuration selected from the group consisting of cis and trans.

33. The compound of claim 32 , having the structure of formula VI, wherein the crossed double bond indicates that the double bond may be of either cis or trans geometry:

34. The compound of claim 32 , having the structure of formula VII, wherein the crossed double bond indicates that the double bond may be of either cis or trans geometry:

35. The compound of claim 32 , having the structure of formula VIII, wherein the crossed double bond indicates that the double bond may have either trans or cis geometry: