Anti-infective agents against intracellular pathogens

1. A compound of Formula I

wherein X is —CF 3 , Ar is

and R is selected from

R′ is is SO 2 CH 2 CH 2 NH 2 , or SO 2 NH 2 or an amino acid attached through the α-carboxyl group selected from the group consisting of L-Lys, D-Lys, β-Ala, L-Lue, L-Ile, Phe, Asn, Glu and Gyl, and

R″ is methyl, ethyl, allyl, CH 2 CH 2 OH, CH 2 CN, CH 2 CH 2 CN, CH 2 CONH 2 ,

or pharmaceutically acceptable salts thereof.

2. The compound of claim 1 wherein the compound has the following Formula VI

or pharmaceutically acceptable salts thereof.

3. The compound of claim 1 wherein the compound has the following Formula VII

or pharmaceutically acceptable salts thereof.

4. The compound of claim 1 wherein the compound has the following Formula XIV

XIV

N4NBS

R″ =

MW 657.66

N4BPS

R″ =

MW 688.72

N4BBS

R″ =

MW 691.56

N4MBS

R″ =

MW 626.69

N4ME

R″ = Me

MW 486.53

N4E

R″ = Et

MW 500.56

N4ALL

R″ = Allyl

MW 512.57

N4HE

R″ = CH2CH2OH

MW 516.56

N4ACN

R″ = CH2CN

MW 511.54

N4PCN

R″ = CH2CH2CN

MW 525.57

N4ETFM

R″ = CH2CH2CF3

MW 568.56

N4AA

R″ = CH2CONH2

or pharmaceutically acceptable salts thereof.

5. A compound of the following Formula IX

or pharmaceutically acceptable salts thereof.

6. A method of inducing apoptosis in cancer cells selected from the group consisting of leukemia, non-small cell lung cancer, colon cancer, central nervous system cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, and breast cancer cells, the method comprising the step of contacting a therapeutically effective amount of a compound of Formula I

wherein X is —CF 3 , Ar is

and R is selected from

 where

R′ is is SO 2 CH 2 CH 2 NH 2 , or SO 2 NH 2 or an amino acid attached through the α-carboxyl group selected from the group consisting of L-Lys, D-Lys, β-Ala, L-Lue, L-Ile, Phe, Asn, Glu and Gyl, and

R″ is methyl, ethyl, allyl, CH 2 CH 2 OH, CH 2 CN, CH 2 CH 2 CN, CH 2 CONH 2 ,

or pharmaceutically acceptable salts thereof, with the rapidly proliferating cells.

7. A method for treating, inhibiting , or delaying the onset of cancer, wherein the cancer is selected from the group consisting of leukemia, non-small cell lung cancer, colon cancer, central nervous system cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, and breast cancer, in a subject in need of such treatment, the method comprising administering a therapeutically effective amount of a compound of Formula I:

wherein X is —CF 3 , Ar is

and R is selected from

 where

R′ is is SO 2 CH 2 CH 2 NH 2 , or SO 2 NH 2 or an amino acid attached through the α-carboxyl group selected from the group consisting of L-Lys, D-Lys, β-Ala, L-Lue, L-Ile, Phe, Asn, Glu and Gyl, and

R″ is methyl, ethyl, allyl, CH 2 CH 2 OH, CH 2 CN, CH 2 CH 2 CN, CH 2 CONH 2 ,

or pharmaceutically acceptable salts thereof, to the subject in need of such treatment.

8. The method of claim 7 wherein the subject is a human.

9. A method of inducing autophagy in cells infected by an intracellular bacteria comprising administering to a subject diagnosed with a disease caused by the bacteria a therapeutically effective amount of at least one compound selected from Formula I, VI, VII, IX, and XIV.

10. The method according to claim 9 , wherein the subject is an animal.

11. The method according to claim 10 , wherein the subject is a human.

12. The method according to claim 9 , wherein the bacteria is chosen from Mycobacterium tuberculosis, Francisella tularensis, Streptococcus pyogenes, Rickettsiae spp., and Salmonella typhimurium.

13. A method of reducing the release of bacterial endotoxins in a subject comprising administering to a subject that has undergone antibiotic treatment a therapeutically effective amount of at least one compound selected from Formula I, VI, VII, IX, and XIV.

14. The method according to claim 13 , wherein the subject is an animal.

15. The method according to claim 14 , wherein the subject is a human.