Substituted quinolone carboxylic acids, their derivatives, site of action, and uses thereof

1. A compound having the Formula I:

or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:

R 1 is selected from the group consisting of hydrogen; an optionally substituted alkyl, and aralkyl;

each R 2 is selected from the group consisting of hydrogen and optionally substituted alkyl;

each R 3 is selected from the group consisting of hydrogen, optionally substituted alkyl; a group OR 11 and NR 12 R 13 ;

R 5 , R 7 and R 8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen;

R 9 and R 10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl; or R 9 and R 10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;

R 11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl;

R 12 and R 13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl; or R 12 and R 13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;

with the proviso that when R 9 and R 10 are taken together to form a piperazinyl ring, R 7 is Cl, R 3 is OR 11, R 11 is H, R 5 and R 8 are H, then R 1 is not Et; with the further proviso that when R 9 and R 10 taken together to form 4-methylpiperazine, R 7 is Cl, R 3 is OR 11, R 11 is H, and R 5 and R 8 are H, then R 1 is not Et; and with the further proviso that when R 9 and R 10 are taken together to form a morpholinyl ring, R 1, R 2, R 5, R 7, R 8 are H, R 3 is NR 12 R 13 and either R 12 or R 13 is H, the other is not n-butyl.

2. A compound having the Formula II:

or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein: R 1 is selected from the group consisting of hydrogen; an optionally substituted alkyl, and aralkyl; each R 2 is selected from the group consisting of hydrogen and optionally substituted alkyl; R 5 , R 7 and R 8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen; R 9 and R 10 are independently selected from the group consisting of optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl; or R 9 and R 10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;

with the proviso that when R 9 and R 10 are taken together to form piperazinyl ring, R 7 is Cl, R 5 and R 8 are H, then R 1 is not Et; and with the further proviso that when R 9 and R 10 are taken together to form 4-methylpiperazinyl, R 7 is Cl, and R 5 and R 8 are H, then R 1 is not Et.

3. A compound having the Formula III:

or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein: R 1 , R 2 , R 5 , R 7 , R 8 , R 9 are as defined in claim 1 ; n is an integer 0, 1, 2, 3 or 4.

4. The compound of claim 3 , wherein n is 2.

5. The compound of claim 3 , wherein R 1 is alkyl, R 2 , R 5 and R 8 are hydrogen and R 7 is halogen.

6. A compound of claim 1 , wherein said compound is: 7-Chloro-1-ethyl-6-1,2,3,4-tetrahydronaphthyl-1-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; (R)-7-Chloro-1-ethyl-6-(1,2,3,4-tetrahydronaphthyl-1-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; (S)-7-Chloro-1-ethyl-6-(1,2,3,4-tetrahydronaphthyl-1-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(1-aminoindanyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(2-aminoindanyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(benzylamino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(phenethyl-2-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-[4-methoxy(phenethylamino)]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-[3-methoxy(phenethylamino)]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-[2-methoxy(phenethylamino)]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-[4-bromo(phenethylamino)]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-[4-chloro(phenethylamino)]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(3-phenylpropylamino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(4-phenylbutylamino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(4-phenylbutyl-2-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(2-phenylpropylamino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(2-phenoxyethylamino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; or 7-Chloro-1-methyl-6-(1,2,3,4-tetrahydronaphthyl-1-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; or a pharmaceutically acceptable salt, prodrug or solvate thereof.

7. A pharmaceutical composition, comprising the compound of Formula I:

or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein: R 1 is selected from the group consisting of hydrogen; an optionally substituted alkyl, and aralkyl; each R 2 is selected from the group consisting of hydrogen and optionally substituted alkyl; each R 3 is selected from the group consisting of hydrogen, optionally substituted alkyl; a group OR 11 and NR 12 R 13 ; R 5 , R 7 and R 8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen; R 9 and R 10 are independently selected from the group consisting of optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl; or R 9 and R 10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring. R 11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl; R 12 and R 13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl; or R 12 and R 13 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring; and a pharmaceutically-acceptable carrier selected from the group consisting of excipients and auxiliaries;

with the proviso that when R 9 and R 10 are taken together to form piperazinyl ring, R 7 is Cl, R 3 is OR 11 , R 11 is H, R 5 and R 8 are H, then R 1 is not Et; with the further proviso that when R 9 and R 10 are taken together to form 4-methylpiperazine, R 7 is Cl, R 3 is OR 11 , R 11 is H, and R 5 and R 8 are H, then R 1 is not Et; and with the further proviso that when R 9 and R 10 are taken together to form a morpholinyl ring, R 1 , R 2 , R 5 , R 7 , R 8 are H, R 3 is NR 12 R 13 and either R 12 or R 13 is H, the other is not n-butyl.

8. The composition of claim 7 , wherein the compound comprises a compound having the Formula I:

or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein: R 1 is selected from the group consisting of hydrogen; an optionally substituted alkyl, and aralkyl; each R 2 is selected from the group consisting of hydrogen and optionally substituted alkyl; each R 3 is selected from the group consisting of hydrogen, optionally substituted alkyl; a group OR 11 and NR 12 R 13 ; R 5 , R 7 and R 8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen; R 9 and R 10 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl; or R 9 and R 10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring; R 11 is selected from the group consisting of hydrogen, an alkali metal, a negative charge and optionally substituted alkyl; R 12 and R 13 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, aryl, cycloalkyl and cycloaralkyl; or R 2 and R 3 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;

with the proviso that when R 9 and R 10 are taken together to form a piperazinyl ring, R 7 is Cl, R 3 is OR 11, R 11 is H, R 5 and R 8 are H, then R 1 is not Et; with the further proviso that when R 9 and R 10 are taken together to form 4-methylpiperazinyl, R 7 is Cl, R 3 is OR 11, R 11 is H, and R 5 and R 8 are H, then R 1 is not Et; and with the further proviso that when R 9 and R 10 are taken together to form a morpholinyl ring, R 1 , R 2 , R 5 , R 7 , R 8 are H, R 3 is NR 12 R 13 and either R 12 or R 13 is H, the other is not n-butyl.

9. The composition of claim 7 , wherein the compound comprises a compound having the Formula II:

or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein: R 1 is selected from the group consisting of hydrogen; an optionally substituted alkyl, and aralkyl; each R 2 is selected from the group consisting of hydrogen and optionally substituted alkyl; R 5 , R 7 and R 8 are independently selected from the group consisting of hydrogen, an optionally substituted alkyl, and halogen; R 9 and R 10 are independently selected from the group consisting of optionally substituted alkyl, aralkyl, cycloalkyl and cycloaralkyl; or R 9 and R 10 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring;

with the proviso that when R 9 and R 10 are taken together to form a piperazinyl, R 7 is Cl, R 5 and R 8 are H, then R 1 is not Et; and with the further proviso that when R 9 and R 10 are taken together to form 4-methylpiperazinyl, R 7 is Cl, and R 5 and R 8 are H, then R 1 is not Et.

10. The composition of claim 7 , wherein the compound comprises a compound having the Formula III: or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein: R 1 , R 2 , R 5 , R 7 , R 8 , R 9 are as defined in claim 1 ; n is an integer 0, 1, 2, 3 or 4.

11. The composition of claim 10 , wherein n is 2.

12. The composition of claim 10 , wherein R 1 is alkyl, R 2 , R 5 and R 8 are hydrogen and R 7 is halogen.

13. The composition of claim 7 , wherein the compound is: 7-Chloro-1-ethyl-6-(1,2,3,4-tetrahydronaphthyl-1-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; (R)-7-Chloro-1-ethyl-6-(1,2,3,4-tetrahydronaphthyl-1-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; (S)-7-Chloro-1-ethyl-6-(1,2,3,4-tetrahydronaphthyl-1-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(1-aminoindanyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(2-aminoindanyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(benzylamino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(phenethyl-2-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-[4-methoxy(phenethylamino)]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-[3-methoxy(phenethylamino)]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-[2-methoxy(phenethylamino)]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-[4-bromo(phenethylamino)]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-[4-chloro(phenethylamino)]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(3-phenylpropylamino)-4-oxo-1,4-dihydroquinoline-3-car-boxylic acid; 7-Chloro-1-ethyl-6-(4-phenylbutylamino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(4-phenylbutyl-2-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(2-phenylpropylamino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(2-phenoxyethylamino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; or 7-Chloro-1-methyl-6-(1,2,3,4-tetrahydronaphthyl-1-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt, prodrug or solvate thereof.

14. The method of claim 9 , wherein the compound is: 7-Chloro-1-ethyl-6-(1,2,3,4-tetrahydronaphthyl-1-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; (R)-7-Chloro-1-ethyl-6-(1,2,3,4-tetrahydronaphthyl-1-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; (S)-7-Chloro-1-ethyl-6-(1,2,3,4-tetrahydronaphthyl-1-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(1-aminoindanyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(2-aminoindanyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(benzylamino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(phenethyl-2-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-[4-methoxy(phenethylamino)]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-[3-methoxy(phenethylamino)]-4-oxo-1,4-dihydroquinoline--3-carboxylic acid; 7-Chloro-1-ethyl-6-[2-methoxy(phenethylamino)]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-[4-bromo(phenethylamino)]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-[4-chloro(phenethylamino)]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(3-phenylpropylamino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(4-phenylbutylamino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(4-phenylbutyl-2-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(2-phenylpropylamino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; 7-Chloro-1-ethyl-6-(2-phenoxyethylamino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; or 7-Chloro-1-methyl-6-(1,2,3,4-tetrahydronaphthyl-1-amino)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt, prodrug or solvate thereof.