5-substituted-2-imino-thiazolidinone compounds and their use as inhibitors of bacterial infection

1. A method for inhibiting Gram-negative bacterial pathogenesis associated with Type II and Type III secretion systems, comprising administering an effective amount of a compound to a subject in need thereof, wherein the compound has the formula:

wherein,

R 1 is selected from the group consisting of:

(a) substituted and unsubstituted aryl,

(b) substituted and unsubstituted heteroaryl,

(c) substituted and unsubstituted alkyl, and

(d) substituted and unsubstituted cycloalkyl;

R 2 is substituted or unsubstituted aryl; and

R 3 is —CH(R 4 )-Q-CH(R 5 )—Y, and Q is —C(═O)NH—, and Y is —C(═O)NH 2 , wherein R 4 and R 5 are independently selected from the group consisting of natural and non-natural amino acid side chains.

2. The method of claim 1 , wherein R 1 is selected from the group consisting of phenyl and substituted phenyl.

3. The method of claim 1 , wherein R 1 is phenyl substituted at one or more of positions 3, 4, and 5 positions with one or more of —OR 11 , —NR 11 R 12 , —SR 11 , and halogen, wherein R 11 and R 12 are independently selected from the group of consisting of:

(a) hydrogen,

(b) substituted and unsubstituted alkyl,

(c) substituted and unsubstituted cycloalkyl,

(d) substituted and unsubstituted aryl,

(e) substituted and unsubstituted heteroaryl, and

(f) —C(═O)R 13 ,

wherein R 13 is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, and substituted and unsubstituted aryl.

4. The method of claim 1 , wherein R 1 is 4-hydroxy-3,5-dimethoxyphenyl.

5. The method of claim 1 , wherein R 1 is morpholinocarbamoylphenyl.

6. The method of claim 1 , wherein R 2 is selected from the group consisting of phenyl and substituted phenyl.

7. A method for inhibiting Gram-negative bacterial pathogenesis associated with Type II and Type III secretion systems, comprising administering an effective amount of a compound to a subject in need thereof, wherein the compound has the formula:

wherein,

R 1 is selected from the group consisting of:

(a) 4-hydroxy-3,5-dimethoxyphenyl, and

(b) morpholinocarbamoylphenyl;

R 2 is substituted or unsubstituted aryl; and

R 3 is selected from the group consisting of:

(a) hydrogen,

(b) substituted or unsubstituted alkyl,

(c) substituted or unsubstituted cycloalkyl,

(d) substituted or unsubstituted aryl,

(e) substituted or unsubstituted heteroaryl,

(f) —CH(R 4 )—W—Y,

wherein W is selected from the group consisting of:

(i) Q-CH(R 5 ), wherein R 4 and R 5 are independently selected from the group consisting of natural and non-natural amino acid side chains, and Q is selected from the group consisting of —C(═O)NH—, —C(═O)O—, —SO 2 NH—, and —P(O)(OR 8 )NH—, wherein R 8 is selected from the group consisting of hydrogen and substituted or unsubstituted alkyl, and

(ii) C(═O)NR 6 CH(R 7 ), wherein R 6 and R 7 taken together with the carbon and the nitrogen atoms to which they are attached form a 5- to 7-membered ring that optionally includes one or more heteroatoms, and

wherein Y is selected from the group consisting of —C(═O)NH 2 , —C(═O)OH, —SO 2 NH 2 ,and —P(O)(OR 8 )NH 2 , wherein R 8 is selected from the group consisting of hydrogen and substituted or unsubstituted alkyl, and

(g) —(CH 2 ) n N(R 9 )X(CH 2 ) m R 10 , wherein n is an integer from 1 to 8, m is an integer from 1 to 8, X is selected from the group consisting of C(═O), N(C═O)OH, N(C═NH)NH, and CH 2 , R 9 is hydrogen or substituted or unsubstituted alkyl, and R 10 is heterocyclyl.