TRANSCRIPTION FACTOR MODULATING COMPOUNDS AND METHODS OF USE THEREOF

A compound of formula (Va):

I 7 R 1 R N/ >---R2 R 4 (Va) wherein R I is OH, OCOCO 2 H, or a substituted or unsubstituted straight or branched Ct-Cs alkyloxy group; R 2 is H, CO 2 (CI-C 5 substituted or unsubstituted, straight or branched alkyl), or a substituted or unsubstituted aryl group; and R 4, R s, R 6, and R 7 are independently selected from the group consisting of H, (CI-C 5 substituted or unsubstituted, straight or branched alkyl), CO 2(C 1-Cs substituted or unsubstituted, straight or branched alkyl), CO(CI-Cs substituted or unsubstituted, straight or branched alkyl), CO(substituted or unsubstituted aryl or heteroaryl), CO(C 3-C 6 substituted or unsubstituted cycloalkyl), O(C -Cs substituted or unsubstituted, straight or branched alkyl), C(NOH)(CI-Cs substituted or unsubstituted, straight or branched alkyl), substituted or unsubstituted amino, CO 2 H, CN, NO 2 , CONH 2 , (CO)(NHOH), and halogen; provided that when R 6 is NO 2 and R 2 is unsubstituted phenyl, then R 1 is not O(CHCH 3)(CO 2)CH 2 CH 3 or OCH 2 CO 2 H; provided that when R 6 is H or NO 2 , then R is not a phenyl-substituted alkyloxy group; provided that when R l is OH, R 2 is unsubstituted phenyl, R 5 and R 7 is hydrogen, and R 6 is NO 2 , then R 4 is not NO 2 ; provided that when R 4, R 5, R 6, and R 7 are all H and R 2 is para-methoxyphenyl, then R is not OH; and provided that when R 4, R 5, R 6, and R 7 are all H and R 2 is unsubstituted phenyl, then R I is not OCH 2 CO 2 CH 2 CH 3 ; and pharmaceutically acceptable salts thereof.

2. The compound of claim 1, wherein R 4, R 5, and R 7 are all H.

3. The compound of claim 2, wherein R is selected from the group consisting of OH, O(CR'R")I_ 3 H, O(CR'R")I_ 3 OH, O(CR'R")I3 CO 2 H, O(CR'R")I3 CO 2 (CR'R")I3 H, O(CR'R")I3(CO)NH 2, O(CR'R")I3 (CNH)NH 2 , OCOCO 2 H, O(CR'R")t3 SO 3 H, O(CR'R")I3 OSOsH, O(CR'R")I3 PO 3 H, O(CR'R")I3 OPO 3 H, O(CR'R')I3 N[(CR'R") 03 H] 2, O(CR'R")I_ 3 (CO)(NHOH), and O(CR'R") 1 _ 3 (heteroaryl); wherein R' and R" are each independently H, a C -C 3 alkyl, C 2 -C 3 alkenyl, or C 2-C 3 alkynyl group.

4. The compound of claim 3, wherein R' and R" is H or CH 3 .

5. The compound of any one of claims 1-4, wherein R I is O(CR'R") 1 _ 3 (heteroaryl).

6. The compound of claim 5, wherein said heteroaryl group is pyrrolyl, furanyl, thiophenyl, thiazolyl, isothiaozolyl, imidazolyl, triazolyl, tetrazolyl, pyrazolyl, oxazolyl, isooxazolyl, pyridinyl, pyrazinyl, pyfidazinyl, or pyfimidinyl group.

7. The compound of any one of claims 1-6, wherein R 2 is a substituted or unsubstituted aryl group.

8. The compound of claim 7, wherein said aryl group substituted or unsubstituted phenyl, pyrrolyl, furanyl, thiophenyl, thiazolyl, isothiaozolyl, imidazolyl, triazolyl, tetrazolyl, pyrazolyl, oxazolyl, isooxazolyl, pyfidinyl, pyrazinyl, pyridazinyl, or pyrimidinyl.

9. The compound of claims 1-9, wherein R 6 is H, (CR'R")I_ 3 H, (CR'R")I_ 3 OH, (CR'R")t_ 3 NH 2, (NOH)(CR'R")I_sH, CO(CR'R") 0 _ 3 NH 2 , CO(CR'R")t_ 3 H, CO(CR'R")I_sOH, CO(CR'R") 0 _ 3 CF 3 , (CR'R") 0_ 3 N[(CR'R") 0_ 3 H]:, CO(substituted or unsubstituted heteroaryl), CO(C 3-C 6 substituted or unsubstituted cycloalkyl), O(CR'R")I_ 3 H, CO(substituted or unsubstituted phenyl), CO 2 (CR'R") 0 -sH, CN, NO 2 , F, CI, Br, or I, wherein R' and R" are each independently H, a CI-C 3 alkyl, C 2 -C 3 alkenyl, or C 2-C 3 alkynyl group.

10. The compound of claim 9, wherein R' and R" are independently H or CH 3 .

12. The compound of any one of claims 1-10, wherein R 6 is CO(substituted or unsubstituted heteroaryl).

13. The compound of claim 12, wherein said heteroaryl is pyrrolyl, furanyl, thiophenyl, thiazolyl, isothiaozolyl, imidazolyl, triazolyl, tetrazolyl, pyrazolyl, oxazolyl, isooxazolyl, pyridinyl, pyrazinyl, pyridazinyl, or pyrimidinyl.

14. The compound of claim 1, R l is OH.

15. The compound of claim 14, wherein R 4, R 5 and R 7 are each hydrogen.

16. The compound of claim 15, wherein R 6 is NO 2 .

17. The compound of claim 16, wherein R 2 is substituted aryl.

18. The compound of claim 17, wherein said substituted aryl is substituted phenyl.

19. A compound selected from the group consisting of:

or a pharmaceutically acceptable salts thereof.

20. A pharmaceutical composition comprising a compound of any one of claims and a pharmaceutically acceptable carrier.

21. A method for reducing antibiotic resistance of a microbial cell, comprising contacting said cell with a transcription factor modulating compound of the formula I 7 R 1 RS N/ -R2 R 4 (Va) wherein R is OH, OCOCOEH, or a substituted or unsubstituted straight or branched C,-C alkyloxy group; R 2 is H, CO 2 (C,-Cs substituted or unsubstituted, straight or branched alkyl), substituted or unsubstituted awl group; and R 4, R 5, R 6, and R 7 are independently selected from the group consisting of H, (CI-C 5 substituted or unsubstitut¢d, straight or branched alkyl), CO 2(C -C 5 substituted or unsubstituted, straight or branched alkyD, CO(CI-C 5 substituted or unsubstituted, straight or branched alkyl), CO(substituted or unsubstituted aryl or heteroaryl), CO(C 3-C 6 substituted or unsubstituted cycloalkyl), O(Ci-C 5 substituted or unsubstituted, straight or branched alkyl), C(NOH)(CI-C 5 substituted or unsubstituted, straight or branched alkyl), substituted or unsubstituted amino, CO 2 H, CN, NO 2 , CONH 2 , (CO)(NHOH), and halogen; provided that when R 6 is NO 2 and R 2 is unsubstituted phenyl, then R I is not O(CHCH 3)(CO 2)CH 2 CH 3 or OCH 2 CO 2 H; provided that when R 6 is H or NO 2 , then R is not a phenyl-substituted alkyloxy group; provided that when R I is OH, R 2 is unsubstituted phenyl, R s and R 7 is hydrogen, and R 6 is NO 2 , then R 4 is not NO 2 ; provided that when R 4, R 5, R 6, and R 7 are all H and R 2 ispara-methoxyphenyl, then R I is not OH; and provided that when R 4, R 5, R 6, and R 7 are all H and R 2 is unsubstituted phenyl, then R t is not OCH 2 CO 2 CH 2 CH 3 ; such that the antibiotic resistance of said cell is reduced.

22. A method for modulating a transcription, comprising contacting a transcription factor with a transcription factor modulating compound of the formula (Va):

I 7 R 1 R 4 wherein R* is OH, OCOCO 2 H, or a substituted or alkyloxy group; R. 2 is H, CO 2 (CI-Cs substituted or substituted or unsubstituted aryl group; and R 4, R 5, R 6, and R 7 are independently (Ci-Cs substituted or unsubstituted, straight or CO 2(Ct-Cs substituted or unsubstituted, straight (Va) unsubstituted straight or branched Ci-Cs unsubstituted, straight or branched alkyl), or a selected from the group consisting of H, branched alkyl), or branched alkyl), CO(CI-C 5 substituted or unsubstituted, straight or branched alkyl), CO(substituted or unsubstituted aryl or heteroaryl), CO(C 3-C 6 substituted or unsubstituted cycloalkyl), O(CI-C 5 substituted or unsubstituted, straight or branched alkyl), C(NOH)(CI-C 5 substituted or unsubstituted, straight or branched alkyl), substituted or unsubstituted amino, CO 2 H, CN, NO 2 , CONH 2 , (CO)(NHOH), and halogen; provided that when R 6 is NO 2 and R 2 is unsubstituted phenyl, then R I is not O(CHCH 3)(CO 2)CH 2 CH 3 or OCH 2 CO 2 H; provided that when R 6 is H or NO 2 , then R l is not a phenyl-substituted alkyloxy group; provided that when R t is OH, R 2 is unsubstituted phenyl, R 5 and R 7 is hydrogen, and R 6 is NO 2 , then R 4 is not NO 2 ; provided that when R 4, R 5, R 6, and R 7 are all H and R 2 is para-methoxyphenyl, then R t is not OH; and provided that when R 4, R 5, R 6, and R 7 are all H and R 2 is unsubstituted phenyl, then R I is not OCH 2 CO 2 CH 2 CH 3 ; such that the transcription is modulated.

23. A method of inhibiting a biofilm, comprising administering a composition comprising a transcription factor modulating compound of the formula I 7 R 1 Rs " N/ R2 R 4 (Va) wherein R is OH, OCOCO 2 H, or a substituted or unsubstituted straight or branched Ct-C alkyloxy group; R 2 is H, CO 2 (CI-C 5 substituted or unsubstituted, straight or branched alkyl), or a substituted or unsubstituted aryl group; and R 4, R 5, R 6, and R 7 are independently selected from the group consisting of H, (Ct-C 5 substituted or unsubstituted, straight or branched alkyl), CO 2(Ct-C 5 substituted or unsubstituted, straight or branched alkyl), CO(CI-C 5 substituted or unsubstituted, straight or branched alkyl), CO(substituted or unsubstituted aryl or heteroaryl), CO(C 3-C 6 substituted or unsubstituted cycloalkyl), O(CvC 5 substituted or unsubstituted, straight or branched alkyl), C(NOH)(C,-C 5 substituted or unsubstituted, straight or branched alkyl), substituted or unsubstituted amino, CO 2 H, CN, NO 2 , CONH 2 , (CO)(NHOH), and halogen; provided that when R 6 is NO 2 and R 2 is unsubstituted phenyl, then R l is not O(CHCH 3 )(CO 2 )CH 2 CH 3 or OCH 2 CO 2 H; provided that when R 6 is H or NO 2 , then R l is not a phenyl-substituted alkyloxy group; provided that when R I is OH, R 2 is unsubstituted phenyl, R 5 and R 7 is hydrogen, and R 6 is NO 2 , then R 4 is not NO 2 ; provided that when R 4, R 5, R 6, and R 7 are all H and R 2 is para-methoxyphenyl, then R t is not OH; and provided that when R 4, R 5, R 6, and R 7 are all H and R 2 is unsubstituted phenyl, then R is not OCH 2 CO 2 CH 2 CH 3 ; such that said biofilm is inhibited.

24. A method for cleaning and disinfecting contact lenses comprising administering composition comprising an acceptable carrier and a transcription factor modulating compound of the formula (Va):

7 R1 RS N/ >-R2 R 4 (Va) wherein R I is OH, OCOCO 2 H, or a substituted or unsubstituted straight or branched CI-C alkyloxy group; R 2 is H, CO 2 (CI-C 5 substituted or unsubstituted, straight or branched alkyl), or a substituted or unsubstituted aryl group; and R 4, R 5, R 6, and R 7 are independently selected from the group consisting of H, (CI-C 5 substituted or unsubstituted, straight or branched alkyl), CO 2(C 1-C 5 substituted or unsubstituted, straight or branched alkyl), CO(C 1-C 5 substituted or unsubstituted, straight or branched alkyl), CO(substituted or unsubstituted aryl or heteroaryl), CO(C 3-C 6 substituted or unsubstituted cycloalkyl), O(CI-C 5 substituted or unsubstituted, straight or branched alkyl), C(NOH)(CI-C 5 substituted or unsubstituted, straight or branched alkyl), substituted or unsubstituted amino, CO 2 H, CN, NO 2 , CONH 2 , (CO)(NHOH), and halogen; provided that when R 6 is NO 2 and R E is unsubstituted phenyl, then R 1 is not O(CHCH 3)(CO 2)CH 2 CH 3 or OCH 2 CO 2 H; provided that when R 6 is H or NO 2 , then R is not a phenyl-substituted alkyloxy group; provided that when R z is OH, R 2 is unsubstituted phenyl, R 5 and R 7 is hydrogen, and R 6 is NO 2 , then R 4 is not NO 2 ; provided that when R 4, R 5, R 6, and R 7 are all H and R 2 is para-methoxyphenyl, then R I is not OH; and provided that when R 4, R 5, R 6, and R 7 are all H and R 2 is unsubstituted phenyl, then R l is not OCH 2 CO 2 CH 2 CH 3 ; such that said contact lenses are cleaned and disinfected.

25. A method of treating medical indwelling devices comprising administering a composition comprising a transcription factor modulating compound of the formula (Va):

wherein R R is OH, OCOCO 2 H, or a substituted or unsubstituted straight or branched C -C alkyloxy group; R 2 is H, CO 2 (CI-C 5 substituted or unsubstituted, straight or branched alkyl), or a substituted or unsubstituted aryl group; and R 4, R 5, R 6, and R 7 are independently selected from the group consisting of H, (CI-C 5 substituted or unsubstituted, straight or branched alkyl), CO 2(C 1-C 5 substituted or unsubstituted, straight or branched alkyl), CO(CI-C 5 substituted or unsubstituted, straight or branched alkyl), CO(substituted or unsubstituted aryl or heteroaryl), CO(C 3-C 6 substituted or unsubstituted cycloalkyl), O(CI-C 5 substituted or unsubstituted, straight or branched alkyl), C(NOH)(CI-C 5 substituted or unsubstituted, straight or branched alkyl), substituted or unsubstituted amino, CO 2 H, CN, NO 2 , CONH 2 , (CO)(NHOH), and halogen; provided that when R 6 is NO 2 and R 2 is unsubstituted phenyl, then R I is not O(CHCH 3)(CO 2)CH 2 CH 3 or OCH 2 CO 2 H; provided that when R 6 is H or NO 2 , then R I is not a phenyl-substituted alkyloxy group; provided that when R I is OH, R 2 is unsubstituted phenyl, R 5 and R 7 is hydrogen, and R 6 is NO 2 , then R 4 is not NO 2 ; provided that when 4, R 5, R 6, and R 7 are all H and R 2 ispara-methoxyphenyl, then R l is not OH; and provided that when R 4, R 5, R 6, and R 7 are all H and R 2 is unsubstituted phenyl, then R t is not OCH 2 CO 2 CH 2 CH 3 ; such that said medical indwelling devices are treated.

26. A method for treating or preventing a biofilm associated state in a subject, comprising administering to said subject an effective amount of a transcription factor modulating compound of the formula (Va):

7 R1 R 4 (Va) wherein R I is OH, OCOCO 2 H, or a substituted or unsubstituted straight or branched C 1 -C alkyloxy group; R E is H, CO 2 (CI-C 5 substituted or unsubstituted, straight or branched alkyl), or a substituted or unsubstituted aryl group; and R 4, R s, R 6, and R 7 are independently selected from the group consisting of H, (CI-C 5 substituted or unsubstituted, straight or branched alkyl), CO 2(CI-C 5 substituted or unsubstituted, straight or branched alkyl), CO(CI-C 5 substituted or unsubstituted, straight or branched alkyl), CO(substituted or unsubstituted aryl or heteroaryl), CO(C 3-C 6 substituted or unsubstituted cycloalkyl), O(CI-C 5 substituted or unsubstituted, straight or branched alkyl), C(NOH)(CI-C 5 substituted or unsubstituted, straight or branched alkyl), substituted or unsubstituted amino, CO 2 H, CN, NO 2 , CONH 2 , (CO)(NHOH), and halogen; provided that when R 6 is NO 2 and R E is unsubstituted phenyl, then R 1 is not O(CHCH 3 )(COE)CHECH 3 or OCHECOEH; provided that when R 6 is H or NO 2 , then R t is not a phenyl-substituted alkyloxy group; provided that when R I is OH, R 2 is unsubstituted phenyl, R 5 and R 7 is hydrogen, and R 6 is NO 2 , then R 4 is not NO 2 ; provided that when R 4, R 5, R 6, and R 7 are all H and R 2 is para-methoxyphenyl, then R I is not OH; and provided that when R 4, R 5, R 6, and R 7 are all H and R 2 is unsubstituted phenyl, then R I is not OCHECOECHECH 3 ; such that said biofilm associated state in said subject is treated.

27. A method fo r preventing a bacterial associated state in a subject, comprising administering to said subject an effective amount of a transcription factor modulating compound of the formula (Va):

. R 2 : 4 (Va) wherein R l is OH, OCOCO 2 H, or a substituted or unsubstituted straight or branched CI-C alkyloxy group; R 2 is H, CO 2 (C 1 -C 5 substituted or unsubstituted, straight or branched alkyl), or substituted or unsubstituted aryl group; and R 4, R 5, R 6, and R 7 are independently selected from the group consisting of H, (CI-C 5 substituted or unsubstituted, straight or branched alkyl), CO 2(CI-C 5 substituted or unsubstituted, straight or branched alkyl), CO(CI-C 5 substituted or unsubstituted, straight or branched alkyl), CO(substituted or unsubstituted aryl or heteroaryl), CO(C 3-C 6 substituted or unsubstituted cycloalkyl), O(C -C 5 substituted or unsubstituted, straight or branched alkyl), C(NOH)(C:C 5 substituted or unsubstituted, straight or branched alkyl), substituted or unsubstituted amino, CO 2 H, CN, NO 2 , CONH 2 , (CO)(NHOH), and halogen; provided that when R 6 is NO 2 and R 2 is unsubstituted phenyl, then R I is not O(CHCH 3)(COz)CH 2 CH 3 or OCHzCO 2 H; provided that when R 6 is H or NO 2 , then R I is not a phenyl-substituted alkyloxy group; provided that when R t is OH, R 2 is unsubstituted phenyl, R s and R 7 is hydrogen, and R. 6 is NO 2 , then R 4 is not NO 2 ; provided that when R 4, R 5, R 6, and R 7 are all H and R 2 is para-methoxyphenyl, then R l is not OH; and provided that when R 4, R 5, R 6, and R 7 are all H and R 2 is unsubstituted phenyl, then R I is not OCH 2 CO 2 CH 2 CH 3 ; such that the bacterial associated state in said subject is prevented.

28. The method of any one of claims 21-27, wherein R 4, R 5, and R 7 are all H.

29. The method of any one of claims 21-28, wherein R l is selected from the group consisting of OH, O(CR'R")I_sH, O(CR'R")I_ 3 OH, O(CR'R")I_ 3 CO 2 H, O(CR'R")I_ 3 CO 2(CR'R")I_ 3 H, O(CR'R")I_s(CO)NH 2 , O(CR'R")I_ 3(CNH)NH 2, OCOCO 2 H, O(CR'R")I-sSOsH, O(CR'R")I_ 3 OSO 3 H, O(CR'R")I_ 3 POaH, O(CR'R')I_ 3 OPO 3 H, O(CR'R") t_ 3 N[(CR'R") 0 - 3 H] 2 , O(CR'R")I_ 3 (CO)(NHOH), and O(CR'R") 1_ 3(heteroaryl), wherein R' and R" are each independently H, a CI-C 3 alkyl, C 2 -C 3 alkenyl, or C 2-C 3 alkynyl group.

30. The method of claim 29, wherein each R' and R" is independently H or CH 3 .

31. The method of any one of claims 21-30, wherein R 1 is O(CR'R") 1 _ 3 (heteroaryl).

32. The method of claim 31, wherein said heteroaryl is pyrrolyl, furanyl, thiophenyl, thiazolyl, isothiaozolyl, imidazolyl, triazolyl, tetrazolyl, pyrazolyl, oxazolyl, isooxazolyl, pyridinyl, pyrazinyl, pyridazinyl, or pyrimidinyl.

33. The method of any one of claims 21-32, wherein R 2 is substituted or unsubstituted aryl.

34. The method of claim 33, wherein said aryl is a substituted or unsubstituted phenyl, pyrrolyl, furanyl, thiophenyl, thiazolyl, isothiaozolyl, imidazolyl, triazolyl, tetrazolyl, pyrazolyl, oxazolyl, isooxazolyl, pyridinyl, pyrazinyl, pyridazinyl, or pyrimidinyl group.

35. The method of any one of claims 22-36, wherein R 6 is H, (CR'R")I3 H, (CR'R")t_ 3 OH,(CR'R")t_ 3 NH 2, (NOH)(CR'R")I_ 3 H, CO(CR'R") 0 - 3 NH 2 , CO(CR'R")I_ 3 H, CO(CR'R")t_ 3 OH, CO(CR'R") 0 - 3 CF 3 , (CR'R") 0_ 3 N[(CR'R") 03 H] 2, CO(substituted or unsubstituted heteroaryl), CO(C 3-C 6 substituted or unsubstituted cycloalkyl), O(CR'R")I_ 3 H, CO(substituted or unsubstituted phenyl), CO 2 (CR'R") 0 - 3 H, CN, NO 2, F, CI, Br, or I, wherein R' and R" are each independently H, a Ct-C 3 alkyl, C 2 -C 3 alkenyl, or C 2-C 3 alkynyl group.

36. The method of claim 35, wherein each R' and R" is independently H or CH 3 .

37. The method of any one of claims 21-36, wherein R 6 is CO(substituted or unsubstituted heteroaryl).

38. The method of claim 27, wherein said heteroaryl is pyrrolyl, furanyl, thiophenyl, thiazolyl, isothiaozolyl, imidazolyl, triazolyl, tetrazolyl, pyrazolyl, oxazolyl, isooxazolyl, pyridinyl, pyrazinyl, pyridazinyl, or pyrimidinyl group.

39. The method of claim 22, wherein said transcription factor is a helix-turn-helix protein.

40. The method of claim 22, wherein said transcription factor is a transcriptional activation factor.

41. The method of claim 41, wherein said transcriptional activation factor is an AraC family polypeptide or a MarA family polypeptide.

42. The method of any one of claims 21-27, wherein said transcription factor modulating compound is a transcription factor inhibiting compound.

43. The method of any one of claims 21-27, wherein said transcription factor modulating compound is a MarA family polypeptide inhibitor or an AraC family polypeptide inhibitor.

44. The method of any one of claims 21-27, wherein said transcription factor is prokaryotic.

45. The method of claim 44, wherein said MarA family polypeptide is MarA, SoxS, or Rob.

46. The method of claim 21, wherein said microbial cell is selected from the group consisting of Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis, BordeteUa bronchiseptica, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Haemophilus ducreyi, Pasteurella multocida, Pasteurella haemolytica, Branhamella catarrhalis, Helicobacter pylori, Campylobacter fetus, Carnpylobacterjejuni, Campylobacter coli, Borrelia burgdorferi, Vibrio cholerae, Yibrio parahaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Gardnerella vaginalis, Bacteroides fragilis, Bacteroides distasonis, Bacteroides 3452A homology group, Bacteroides vulgatus, Bacteroides ovalus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides eggerthii, Bacteroides splanchnicus, Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Staphylococcus intermedius, Staphylococcus hyicus subsp, hyicus, Staphylococcus haemolyticus, Staphylococcus hominis, and Staphylococcus saccharolyticus.

47. The method of any one of claims 21-27, wherein said compound is selected from the group consisting of:

or a pharmaceutically acceptable salts thereof.

48. The method of claim 26, wherein said biofilm associated state is selected from the group consisting of middle ear infections, cystic fibrosis, osteomyelitis, acne, dental cavities, endocarditis, and prostatitis.

49. The method of claim 23, wherein said composition further comprises a surfactant.

50. The method of claim 49, wherein said surfactant is Sodium Dodecyl Sulfate; Quaternary Ammonium Compounds; alkyl pyridinium iodides; Tween 80, Tween 85, Triton X 100; Brij 56; biological surfactants; Rhamnolipid, Surfactin, Visconsin, or sulfonates.

51. The method of claim 25, wherein said biofilm development is diminished by the administration of said composition.

52. The method of claim 25, wherein said device is selected from the group consisting of catheters, orthopedic devices and implants.

53. The method of any one of claims 21-27, further comprising administering a pharmaceutically acceptable cartier.

54. The method of claim 26 or 27, wherein said subject is a mammal.

55. The method of claim 54, wherein said mammal is a human.

56. The method of claim 54, wherein said subject is immunocompromised.

57. The use of a compound of formula (Va) as defined in any one of claims for the manufacture of a medicament for the treatment of a condition selected from group consisting of:

a) reducing antibiotic resistance of a microbial cell; b) modulating transcription; c) inhibiting a biofilm; d) cleaning and disinfecting contact lenses; e) treating medical indwelling devices; t) treating or preventing a biofilm associated state; or g) treating or preventing a bacterial associated state.

PARATEK PHARMACEUTICALS, INC.

WATERMARK PATENT & TRADE MARK ATTORNEYS