Biodefenses using triazole-containing macrolides

1. A method for acute-exposure treatment of a host animal exposed to one or more organisms selected from the group consisting of Yersinia pestis, Francisella tularensis , and combinations thereof; the method comprising administering a composition comprising one or more compounds

where the compounds are selected from the formula

and pharmaceutically acceptable salts thereof, wherein:

R 10 is hydrogen or acyl;

X is H; and Y is OR 7 ; who R 7 is a monosaccharide or disaccharide, alkyl, aryl, heteroaryl, acyl, or C(O)NR 8 R 9 , where R 8 and R 9 are each independently selected from the group consisting of hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, heteroalkyl, aryl, heteroaryl, alkoxy, dimethylaminoalkyl, acyl, sulfonyl, ureido, and carbamoyl; or X and Y are taken together with the attached carbon to form carbonyl;

V is C(O), C(═NR 11 ), CH(NR 12 , R 13 ), or N(R 14 )Ch 2 , where N(R 14 ) is attached to the C-10 carbon; wherein R 11 is hydroxy or alkoxy, R 12 and R 13 are each independently selected from the group consisting of hydrogen, hydroxy, akyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, ureido, and carbamoyl; R 14 is hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, ureido, or carbamoyl;

W is H, F, Cl, Br, I, or OH;

A is CH 2 , C(O), C(O)O, C(O)NH, S(O) 2 , S(O) 2 NH, C(O)NHS(O) 2 ;

B is (CH 2 ) n where n is an integer ranging from 0-10, or B is an unsaturated carbon chain of 2-10 carbons; and

C is hydrogen, hydroxy, alkyl, aralkyl, arylalkyl, alkoxy, heteroalkyl, aryl, heteroaryl, heteroarylalkyl, acyl, acyloxy, sulfonyl, ureido, or carbamoyl, each of which is optionally substituted.

2. The method of claim 1 wherein where R 7 is 4-nitro-phenylacetyl or 2-pyridylacetyl.

3. The method of claim 1 wherein B is alkenylene.

4. The method of claim 1 wherein V is —C(O)—.

5. The method of claim 1 wherein W is H or F.

6. The method of claim 1 wherein X and Y are taken together with the attached carbon to form carbonyl.

7. The method of claim 1 wherein W is F.

8. The method of claim 1 wherein X and Y are taken together with the attached carbon to form carbonyl; and W is F.

9. The method of claim 1 wherein A is CH 2 , B is (CH 2 ) n , and n is an integer from 2-4.

10. The method of claim 1 wherein C is optionally substituted aryl or optionally substituted heteroaryl.

11. The method of claim 1 wherein C is 3-aminophenyl or 3-pyridinyl.

12. The method of claim 1 wherein R 10 is hydrogen.

13. A method for treating a host animal with a disease caused at least in part by one or more organisims selected from the group consisting of Yersinia pestis, Francisella tularensis , and combinations thereof; the method comprising administering to the host animal a composition comprising one or more compounds

where the compounds are selected from the formula

and pharmaceutically acceptable salts thereof, wherein:

R 10 is hydrogen or acyl;

X is H; and Y is OR 7 ; where R 7 is a monosaccharide or disaccharide, alkyl, aryl, heteroaryl, acyl, or C(O)NR 8 R 9 , where R 8 and R 9 are each independently selected from the group consisting of hydrogen, hydroxyl, alkyl, aralkyl, alkylaryl, heteroalkyl, aryl, heteroaryl, alkoxy, dimethylaminoalkyl, acyl, sulfonyl, ureido, and carbamoyl; or X and Y are taken together with the attached carbon to form carbonyl;

V is C(O), C(═NR 11 ), CH(NR 12 , R 13 ), or N(R 14 )CH 2 , where N(R 14 ) is attached to the C-10 carbon; wherein R 11 is hydroxy or alkoxy, R 12 and R 13 are each independently selected from the group consisting of hydrogen, hydroxy, akyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, ureido, and carbamoyl; R 14 is hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, ureido, or carbamoyl;

W is H, F, Cl, Br, I, or OH;

A is CH 2 , C(O), C(O)O, C(O)NH, S(O) 2 , S(O) 2 NH, C(O)NHS(O) 2 ;

B is (CH 2 ) n where n is an integer ranging from 0-10, or B is an unsaturated carbon chain of 2-10 carbons; and

C is hydrogen, hydroxy, alkyl, aralkyl, arylalkyl, alkoxy, heteroalkyl, aryl, heteroaryl, heteroarylalkyl, acyl, acyloxy, sulfonyl, ureido, or carbamoyl, each of which is optionally substituted.

14. The method of claim 1 wherein the composition comprises a compound of the formula

or a pharmaceutically acceptable salt thereof.

15. The method of claim 1 wherein the composition comprises a compound of the formula

16. A method for treating a disease in a host animal, where the disease is selected from the group consisting of anthax, inhalational anthrax, Legionnaire's Disease, atypical pneumonia, plague, tularemia, pneumonic tularemia, malleus, melioidosis, and combinations thereof, the method comprising administering to the host animal a composition comprising one or more compounds

where the compounds are selected from the formula

and pharmaceutically acceptable salts thereof, wherein:

R 10 is hydrogen or acyl;

X is H; and Y is OR 7 ; where R 7 is a monosaccharide or disaccharide, alkyl, aryl, heteroaryl, acyl, or C(O)NR 8 R 9 , where R 8 and R 9 are each independently selected from the group consisting of hydrogen, hydroxyl, alkyl, aralkyl, alkylaryl, heteroalkyl, aryl, heteroaryl, alkoxy, dimethylaminoalkyl, acyl, sulfonyl, ureido, and carbamoyl; or X and Y are taken together with the attached carbon to form carbonyl;

V is C(O), C(═NR 11 ), CH(NR 12 , R 13 ), or N(R 14 )CH 2 , where N(R 14 ) is attached to the C-10 carbon; wherein R 11 is hydroxy or alkoxy, R 12 and R 13 are each independently selected from the group consisting hydrogen, hydroxyl, akyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, ureido, and carbamoyl; R 14 is hydrogen, hydroxyl, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, ureido, or carbamoyl;

W is H, F, Cl, Br, I, or OH;

A is CH 2 , C(O), C(O)O, C(O)NH, S(O) 2 , S(O) 2 NH, C(O)NHS(O) 2 ;

B is (CH 2 ) n where n is an integer ranging from 0-10, or B is an unsaturated carbon chain of 2-10 carbons; and

C is hydrogen, hydroxy, alkyl, aralkyl, arylalkyl, alkoxy, heteroalkyl, aryl, heteroaryl, heteroarylalkyl, acyl, acyloxy, sulfonyl, ureido, or carbamoyl, each of which is optionally substituted.

17. The method of claim 13 wherein the composition comprises a compound of the formula

or a pharmaceutically acceptable salt thereof.

18. The method of claim 13 wherein the composition comprises a compound of the formula

19. The method of claim 16 wherein the composition comprises a compound of the formula

or a pharmaceutically acceptable salt thereof.

20. The method of claim 16 wherein the composition comprises a compound of the formula