Compounds and methods for treating inflammatory diseases

1. A pharmaceutical composition comprising (a) a therapeutically effective amount of one or more compounds of the formula

or a pharmaceutically acceptable salt thereof, wherein:

R 2 is acyl;

R 3 and R 4 are taken together with the attached oxygen atoms to form a carbonate;

R 5 is hydrogen, alkyl, alkenyl, or alkynyl;

R a is hydrogen, optionally substituted alkyl, acyl, or a monosaccharide; and

Z taken together with the attached carbon forms a carbonyl, imine, oxime, or hydrazone, or Z represents Z a , OR b ; where Z a is H; and R b is hydrogen, acyl, or a monosaccharide, or alkyl or arylalkyl, each of which is optionally substituted; and

(b) a carrier, diluent, or excipient, or a combination thereof;

where the composition is adapted for treating an inflammatory disease of the respiratory system.

2. The composition of claim 1 , wherein at least one compound is of the formula

or a pharmaceutically acceptable salt thereof.

3. The composition of claim 1 , wherein R 2 is acetyl; and R 3 and R 4 are taken together with the attached oxygen atoms to form a carbonate.

4. The composition of claim 1 wherein the disease is selected from the group consisting of chronic obstructive pulmonary disease (COPD), asthma, chronic bronchitis, emphysema, and acute respiratory distress syndrome (ARDS).

5. A pharmaceutical composition comprising (a) a therapeutically effective amount of one or more compounds of the formula

or a pharmaceutically acceptable salt thereof, wherein:

R 2 is acyl;

R 3 and R 4 are in each instance independently selected from the group consisting of hydrogen, acyl, and alkyl, cycloalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, heterocyclylheteroalkyl aryl, aryl alkyl, and arylheteroalkyl, each of which is optionally substituted; or R 3 and R 4 are taken together with the attached oxygen atoms to form a carbonate;

R 5 is hydrogen, alkyl, alkenyl, or alkynyl;

R a is hydrogen, optionally substituted alkyl, acyl, or a monosaccharide; and

Z taken together with the attached carbon forms a carbonyl, imine, oxime, or hydrazone, or Z represents Z a , OR b ; where Z a is H; and R b is an amino containing acyl, or a derivative thereof; and

(b) a carrier, diluent, or excipient, or a combination thereof;

where the composition is adapted for treating an inflammatory disease of the respiratory system.

6. The composition of claim 5 , wherein R 3 and R 4 are both hydrogen.

7. The composition of claim 5 wherein the disease is selected from the group consisting of chronic obstructive pulmonary disease (COPD), asthma, chronic bronchitis, emphysema, and acute respiratory distress syndrome (ARDS).

8. A method for treating an inflammatory disease of the respiratory system in a patient, the method comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising (a) at least one compound is of the formula

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is in each instance independently selected from the group consisting of hydrogen, acyl, and alkyl, cycloalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, heterocyclylheteroalkyl aryl, aryl alkyl, and arylheteroalkyl, each of which is optionally substituted; or R 1 are taken together with the attached nitrogen to form an optionally substituted heterocycle or optionally substituted heteroaryl; or R 1 are taken together with the attached nitrogen to form azido;

R 5 is hydrogen, alkyl, alkenyl, or alkynyl;

R a is hydrogen, optionally substituted alkyl, acyl, or a monosaccharide; and

W is H or F;

X is alkylene, heteroalkylene, a divalent carbocycle, or a divalent heterocycle, each of which is optionally substituted;

Y taken together with the attached carbon forms a carbonyl, imine, oxime, or hydrazone, or Y represents H, OR 5 ; and

X 1 is C═Z, where Z taken together with the attached carbon forms a carbonyl, imine, oxime, or hydrazine; or X 1 is CHOR b , where R b is hydrogen, or acyl, or a monosaccharide, or alkyl or arylalkyl, each of which is optionally substituted; and

(b) optionally one or more carriers, diluents, or excipients, or a combination thereof.

9. The method of claim 8 , wherein at least one of R 1 is hydrogen.

10. The method of claim 8 , wherein at least one of R 1 is acyl group.

11. The method of claim 8 , wherein at least one of R 1 is C 2 -C 6 alkyl or C 3 -C 6 cycloalkyl, each of which is optionally substituted.

12. The method of claim 8 , wherein both R 1 are hydrogen and R a is a monosaccharide.

13. The method of claim 8 , wherein R a is an optionally substituted desmethyl or bisdesmethyl desosamine.

14. The method of claim 13 , at least one of R 1 is hydrogen.

15. The method of claim 13 , wherein at least one of R 1 is acyl group.

16. The method of claim 15 , wherein at least one R 1 is hydrogen.

17. The method of claim 13 , wherein at least one of R 1 is C 2 -C 6 alkyl or C 3 -C 6 cycloalkyl, each of which is optionally substituted.

18. The method of claim 8 , wherein X is alkylene.

19. The method of claim 8 , wherein X 1 is CHOR b , where R b is an amino containing monosaccharide.

20. The method of claim 8 wherein the disease is selected from the group consisting of chronic obstructive pulmonary disease (COPD), asthma, chronic bronchitis, emphysema, and acute respiratory distress syndrome (ARDS).

21. A method for treating an inflammatory disease of the respiratory system in a patient, the method comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising (a) one or more compounds of the formula

or a pharmaceutically acceptable salt thereof, wherein

R 2 is acetyl;

R 3 and R 4 are in each instance independently selected from the group consisting of hydrogen, acyl, and alkyl, cycloalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, heterocyclylheteroalkyl aryl, aryl alkyl, and arylheteroalkyl, each of which is optionally substituted; or R 3 and R 4 are taken together with the attached oxygen atoms to form a carbonate;

R 5 is hydrogen, alkyl, alkenyl, or alkynyl;

R a is hydrogen, optionally substituted alkyl, acyl, or a monosaccharide; and

X 1 is C═Z, where Z taken together with the attached carbon forms a carbonyl, imine, oxime, or hydrazine; or X 1 is CHOR b , where R b is hydrogen, or acyl, or a monosaccharide, or alkyl or arylalkyl, each of which is optionally substituted; and

(b) optionally one or more carriers, diluents, or excipients, or a combination thereof.

22. The method of claim 21 , wherein at least one compound is of the formula

or a pharmaceutically acceptable salt thereof.

23. The method of claim 22 , wherein R 3 and R 4 are both hydrogen.

24. The method of claim 21 , wherein R 3 and R 4 are both hydrogen.

25. The method of claim 21 , wherein R 3 and R 4 are taken together with the attached oxygen atoms to form a carbonate.

26. The method of claim 21 , wherein X 1 is CHOR b , where R b is an amine, amide, carbamate, urea, or guanidine containing acyl.

27. The method of claim 26 , wherein R 3 and R 4 are taken together with the attached oxygen atoms to form a carbonate.

28. The method of claim 21 wherein the disease is selected from the group consisting of chronic obstructive pulmonary disease (COPD), asthma, chronic bronchitis, emphysema, and acute respiratory distress syndrome (ARDS).

29. A compound of the formula

or a pharmaceutically acceptable salt thereof, wherein:

R 2 is acyl;

R 3 and R 4 are taken together with the attached oxygen atoms to form a carbonate;

R 5 is hydrogen, alkyl, alkenyl, or alkynyl;

R a is hydrogen, optionally substituted alkyl, acyl, or a monosaccharide; and

X 1 is C═Z, where Z taken together with the attached carbon forms a carbonyl, imine, oxime, or hydrazine; or X 1 is CHOR b , where R b is hydrogen, or acyl, or a monosaccharide, or alkyl or arylalkyl, each of which is optionally substituted.