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 SO 2 CH 2 CH 2 NH 2 or SO 2 NH 2 or an amino acid attached through a peptide bond including the α-carboxyl group of an amino acid selected from the group consisting of L-Lys, D-Lys, β-Ala, L-Leu, L-Ile, Phe, Asn, Glu and Gly, 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 VIII

or pharmaceutically acceptable salts thereof.

3. The compound of claim 1 wherein the compound has the following formula X

or pharmaceutically acceptable salts thereof.

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

XIII

where

F4ME

R″ = Me

MW

530.51

F4E

R″ = Et

MW

544.54

F4HE

R″ = CH2CH2OH

MW

560.53

F4ETFM

R″ = CH2CH2CF3

MW

612.53

F4ACN

R″ = CH2CN

MW

555.52

F4PCN

R″ = CH2CH2CN

MW

569.54

F4AP

MW

573.53

F4AMO

MW

574.52

F4AMP

MW

587.56

F4AANT

MW

632.54

F4AAT

MW

602.55

F4AA

R″ = CH2CONH2

F4PA

R″ = CH2CH2CONH2

or pharmaceutically acceptable salts thereof.

5. 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 SO 2 CH 2 CH 2 NH 2 or SO 2 NH 2 or an amino acid attached through a peptide bond including the α-carboxyl group of an amino acid selected from the group consisting of L-Lys, D-Lys, β-Ala, L-Leu, L-Ile, Phe, Asn, Glu and Gly, 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.

6. The method of claim 5 , wherein the rapidly proliferating cells are cancer cells, wherein the cancer cells are 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.

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 SO 2 CH 2 CH 2 NH 2 or SO 2 NH 2 or an amino acid attached through a peptide bond including the α-carboxyl group of an amino acid selected from the group consisting of L-Ls, D-Lys, β-Ala, L-Leu, L-Ile, Phe, Asn, Glu and Gly, 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:

wherein X is —CF 3 , Ar is

and R is selected from

R′ is SO 2 CH 2 CH 2 NH 2 or SO 2 NH 2 or an amino acid attached through a peptide bond including the α-carboxyl group of an amino acid selected from the group consisting of L-Ls, D-Lys, β-Ala, L-Leu, L-Ile, Phe, Asn, Glu and Gly, 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.

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, Francisella novicida, Streptococcus pyogenes, Rickettsiae spp., and Salmonella typhimurium.

13. The method according to claim 9 , wherein the disease is a neurodegenerative disease.

14. A method for 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:

wherein X is —CF 3 , Ar is

and R is selected from

R′ is SO 2 CH 2 CH 2 NH 2 or SO 2 NH 2 or an amino acid attached through a peptide bond including the α-carboxyl group of an amino acid selected from the group consisting of L-Ls, D-Lys, β-Ala, L-Leu, L-Ile, Phe, Asn, Glu and Gly, 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.

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

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