Antifungal compounds
The technical field of the invention is in pharmaceutical compounds and methods. In an aspect, the disclosure provides macrolide compounds suitable for use as antifungal agents, as well as methods for their use and compositions containing the same.
1. An antifungal composition formulated in effective unit dosage and comprising an antifungal compound of formula (I)
wherein:
“a” is a double bond that may be present provided that R 5a is not present;
R 1 is selected from alkyl, alkenyl, or is taken together with R 3 or R 3a to form a cycle;
R 3 and R 3a are independently selected from —H, and —OH, or R 3 and R 3a together form ═X, where X is selected from O, C, and N such that ═X and the carbon atom to which it is attached forms a carbonyl, oxime, substituted oxime, imine, substituted imine, hydrazone, substituted hydrazone, terminal olefin, or substituted olefin functional group, or wherein one of R 3 and R 3a is —H and the other is taken together with R 1 or R 5 or R 5a to form a cycle;
R 5 and R 5a are independently selected from —H, —OH, or —OTBS, or R 5 and R 5a together form ═O, or one of R 5 and R 5a is —H and the other is taken together with R 3 or R 3a to form a cycle;
R 7 is a substituted carboxyl selected from:
and R 7a is —H; and
R9 is selected from —H and —OH,
or a pharmaceutically acceptable salt thereof.
2. The composition of claim 1 , wherein the compound has the structure of formula (IA-c):
3. The composition of claim 1 , wherein the compound has the structure of formula (IF):
4. The composition of claim 1 wherein the compound has a structure selected from the group consisting of:
48
49
54
58
59
60
165
166
191
192
194
195
196
197
198
199
201
214
5. The composition of claim 1 wherein the compound has a structure:
48
6. The composition of claim 1 wherein the compound has a structure:
49
7. The composition of claim 1 wherein the compound has a structure:
54
8. The composition of claim 1 wherein the compound has a structure:
58
9. The composition of claim 1 wherein the compound has a structure:
59
10. The composition of claim 1 wherein the compound has a structure:
60
11. The composition of claim 1 wherein the compound has a structure:
165
12. The composition of claim 1 wherein the compound has a structure:
166
13. The composition of claim 1 wherein the compound has a structure:
191
14. The composition of claim 1 wherein the compound has a structure:
192
15. The composition of claim 1 wherein the compound has a structure:
194
16. The composition of claim 1 wherein the compound has a structure:
195
17. The composition of claim 1 wherein the compound has a structure:
196
18. The composition of claim 1 wherein the compound has a structure:
197
19. The composition of claim 1 wherein the compound has a structure:
198
20. The composition of claim 1 wherein the compound has a structure:
199
21. The composition of claim 1 wherein the compound has a structure:
201
22. The composition of claim 1 wherein the compound has a structure:
214
23. A method for treating a patient suffering from a fungal infection, the method comprising administering to the patient an effective amount of a composition of claim 1 .