Aminoglycoside and azole compositions and methods

Patent metadata

Field	Value
Publication number	US-9669044-B2
Application number	US-201414281659-A
Country	US
Kind code	B2
Filing date	May 19, 2014
Priority date	Dec 14, 2010
Publication date	Jun 6, 2017
Grant date	Jun 6, 2017

Abstract

The present invention relates to novel fungicidal compound including an aminoglycoside analog having certain substituents at the 6 position of ring III that exhibit improved antifungal activity but possess minimal antibacterial properties in combination with fungicidal azoles. The aminoglycoside compounds are analogues of kanamycin A. Also provided are methods of synthesizing and methods of using the compounds of the present invention. The compounds of the present invention are useful in treating or preventing fungal disease.

First claim

What is claimed is:

1. A fungicidal composition comprising:
an aminoglycoside compound, or salt thereof having the formula:

wherein:
X is a member selected from the group consisting of O and S;
R 1 is a member selected from the group consisting of R 3 , C(O)OR 3 , S(O) 2 R 3 , S(O) 2 R 4 , S(O)R 3 , P(O) 2 R 3 , and phenyl, wherein phenyl groups may be C 1 to C 6 alkyl substituted;
R 3 is a straight or branched chain C 6 to C 12 alkyl group; and
R 4 is phenyl or C 1 to C 6 alkyl substituted phenyl; and

an azole.

2. The composition according to claim 1 , wherein:
X is O or S;
R 1 is a member selected from the group consisting of S(O) 2 R 3 and S(O) 2 R 4 ,
wherein:
R 3 is C 6 to C 12 straight or branched chain alkyl and
R 4 is phenyl or C 1 to C 6 alkyl substituted phenyl.

3. The composition according to claim 1 , wherein R 1 is C(O)OR 3 .

4. The composition according to claim 1 , wherein R 1 is S(O)R 3 .

5. The composition according to claim 1 , wherein R 1 is P(O) 2 R 3 .

6. The composition according to claim 2 , wherein X is O and R 1 is S(O) 2 R 3 .

7. The composition according to claim 6 , wherein R 3 is C 6 H 13 .

8. The composition according to claim 6 , wherein R 3 is C 8 H 17 .

9. The composition according to claim 2 , wherein X is O and R 1 is S(O) 2 R 4 .

10. The composition according to claim 9 , wherein R 4 is p-tolyl.

11. The composition according to claim 2 , wherein X is S and R 1 is R 3 .

12. The composition according to claim 11 , wherein R 3 is C 8 H 17 .

13. The composition according to claim 1 , wherein the azole is selected from the group consisting of itraconazol, fluconazole, voriconazole, posaconazole, clotrimazol, tioconazole, ketoconazole, metconazole, tebuconazole, and pyraclostrobin.

14. A method of treating a fungal infection which comprises administering to a host in need thereof an effective amount of a fungicidal composition comprising:
an aminoglycoside compound, or salt thereof having the formula:

wherein:
X is a member selected from the group consisting of O and S;
R 1 is a member selected from the group consisting of R 3 , C(O)OR 3 , S(O) 2 R 3 , S(O) 2 R 4 , S(O)R 3 , P(O) 2 R 3 , and phenyl, wherein phenyl groups may be C 1 to C 6 alkyl substituted;
R 3 is a straight or branched chain C 6 to C 12 alkyl group; and

an azole.

15. The method according to claim 14 wherein:
X is O or S;
R 1 is a member selected from the group consisting of S(O) 2 R 3 and S(O) 2 R 4 ,
R 3 is C 6 to C 12 straight or branched chain alkyl, and
R 4 is phenyl or C 1 to C 6 alkyl substituted phenyl.

16. The method according to claim 15 wherein X is O and R 1 is S(O) 2 R 3 .

17. The method according to claim 16 wherein R 3 is C 6 H 13 .

18. The method according to claim 16 wherein R 3 is C 8 H 17 .

19. The method according to claim 14 wherein said host in need thereof is a plant or an animal.

20. The method of claim 14 , wherein the azole is selected from the group consisting of itraconazole, fluconazole, voriconazole, posaconazole, clotrimazole, tioconazole, ketoconazole, metconazole, tebuconazole, and pyraclostrobin.

Assignees

• Takemoto Jon Y
• Chang Cheng-Wei Tom
• Shrestha Sanjib K
• Grilley Michelle
• Univ Utah State

Inventors

• Takemoto Jon Y
• Chang Cheng-Wei Tom
• Shrestha Sanjib K
• Grilley Michelle

Classifications

• A61K31/365

  Lactones · CPC title

• A01N43/16

  with oxygen as the ring hetero atom · CPC title

• A61K31/4196

  1,2,4-Triazoles · CPC title

• A61K31/415

  1,2-Diazoles · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title