Novobiocin analogues having modified sugar moieties

1. Compounds according to Formula I:

wherein R 1 is alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, aralkyl, carboxyl, amido, amino, sulfanyl, sulfenyl, sulfonyl, or ether; or R 1 together with X 2 and the atom to which R 1 is attached form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from oxygen or nitrogen; or R 1 together with X 4 and the atom to which R 1 is attached form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from oxygen or nitrogen;

wherein X 1 is —O—, —CO—, or —NH—;

wherein X 2 is —O—, —NR 18 —, —CR 19 —, or —CO—; and wherein R 18 and R 19 are hydrogen, alkyl, alkenyl, or alkynyl; or X 2 together with R 1 and the atom to which R 1 is attached form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from oxygen or nitrogen;

wherein X 4 is, —CR 20 —, or —N═, wherein R 20 is hydrogen, alkyl, alkenyl, or alkynyl;

wherein X 5 , is —CR 21 — or —N═, wherein R 21 is hydrogen, alkyl, alkenyl, alkynyl, or alkoxy;

wherein X 6 , is —CR 22 — or —N═, wherein R 22 is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, aryl, aralkyl, halogen, or nitro; or X 6 together with X 9 and the carbon at position 7 form a heterocylic ring having 4 to 8 ring members with at least one heteroatom selected from oxygen or nitrogen;

wherein X 8 , is —CR 23 — or —N═, wherein R 23 is hydrogen, alkyl, alkenyl, alkynyl, aryl, alkoxy or halogen;

wherein X 9 is hydroxyl, —O-cycloalkyl substituted with at least one amino, alkyl, halo, or hydroxyl group, —OAc, —O-azasugar, —O-pyridine, —O-pyrrolino, —O-alcohol, alcohol, ester, amino, amido, carbamate, phosphate ester, or mesylate; and

wherein at least one of X 2 , X 4 , X 5 , X 6 , X 8 is not —CR—.

2. The compounds of claim 1 wherein X 9 is —O-cycloalkyl substituted with at least one amino, alkyl, halo, or hydroxyl group, —OAc, —O-azasugar, —O-pyridine, —O-pyrrolino, —O-alcohol, alcohol, ester, amino, amido, carbamate, or phosphate ester.

3. The compound of claim 1 wherein the compounds are coumarin compounds wherein X 1 is —O— and X 2 is —CO—.

4. The compounds of claim 1 wherein X 9 is an —O-azasugar.

5. The compounds of claim 4 wherein said azasugar is 1,3-azasugar or 1,4-azasugar.

6. The compounds of claim 2 wherein X 9 is —OAc.

7. The compounds of claim 1 which are selected from the group consisting of:

8. The compounds of claim 1 wherein X 9 is —O-cyclohexyl substituted with at least one hydroxyl.

9. The compounds of claim 1 wherein R 1 is an amido which is NR′COR″, and R′ is hydrogen or alkyl and R″ is aryl according to:

wherein R 24 and R 25 are independently hydrogen, alkyl, amino, halo, hydroxy, or alkoxy.

10. The compounds according to claim 1 wherein R 1 is an amido which is NR′COR″, and wherein R′ is hydrogen and R″ is aryl according to:

wherein X is ether or amino;

wherein R 24 is alkoxy;

wherein R 25 is hydrogen, hydroxy, alkoxy, or aryloxy; and

wherein R 26 is hydrogen, alkoxy, aryloxy, or amino.

11. The compounds according to claim 1 wherein R 1 is an amido which is NR′COR″, and wherein R′ is hydrogen and R″ is a an indole according to:

or a R″ is a pendant aryl according to:

12. The compounds of claim 1 wherein X 4 is —CH—, X 5 is —CR 21 —, X 6 is —CR 22 —, X 8 , is —CR 23 — according to:

wherein R 1 is an amido which is NR′COR″, and R′ is hydrogen and R″ is alkyl, alkenyl, alkynyl, alkoxy, carbocyclic, heterocylic, aryl, or aralkyl;

wherein X 1 is —O—, —CO—, or —NH—;

wherein X 2 is —O—, —NH—, —CR 19 — or —CO—, wherein R 19 is hydrogen, alkyl, alkenyl, alkynyl;

wherein R 21 is hydrogen, alkyl, alkenyl, alkynyl, or alkoxy;

wherein R 22 is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, aryl, aralkyl, halogen, or nitro;

wherein R 23 is hydrogen, alkyl, alkenyl, alkynyl, aryl, alkoxy, or halogen;

wherein X 9 is hydroxyl, —O-cycloalkyl substituted with at least one amino, alkyl, halo, or hydroxyl group, —OAc, —O-azasugar, —O-pyridine, —O-pyrrolino, —O-alcohol, alcohol, ester, amino, amido, carbamate, phosphate ester, or mesylate.

13. The compound of claim 12 wherein the compounds are coumarin compounds wherein X 1 is —O— and X 2 is —CO—.

14. The compounds of claim 12 wherein X 9 is an —O-azasugar.

15. The compounds of claim 14 wherein said azasugar is 1,3-azasugar or 1,4-azasugar.

16. The compounds of claim 12 wherein X 9 is —OAc.

17. The compounds of claim 12 wherein X 9 is —O-cyclohexyl substituted with at least one hydroxyl.

18. The compounds of claim 12 wherein R 1 is an amido which is NR′COR″, and R′ is hydrogen or alkyl and R″ is aryl according to:

wherein R 24 and R 25 are independently hydrogen, alkyl, amino, halo, hydroxy, or alkoxy.

19. The compounds according to claim 12 wherein R 1 is an amido which —NHCOCH 3 or is —NR′COR″, and R′ is hydrogen and R″ is aryl according to:

wherein R 24 and R 25 are alkoxy.

20. The compounds according to claim 12 wherein R 1 is an amido which is NR′COR″, and wherein R′ is hydrogen and R″ is aryl according to:

wherein R 24 and R 25 are independently hydrogen, alkyl, or alkoxy.

21. The compounds according to claim 12 wherein R 1 is an amido which is NR′COR″, and wherein R′ is hydrogen and R″ is aryl according to:

wherein X is ether or amino;

wherein R 24 is alkoxy;

wherein R 25 is hydrogen, hydroxy, alkoxy, or aryloxy; and

wherein R 26 is hydrogen, alkoxy, aryloxy, or amino.

22. The compounds according to claim 12 wherein R 1 is an amido which is NR′COR″, and wherein R′ is hydrogen and R″ is a an indole according to:

or a R″ is a pendant aryl according to:

23. The compounds of claim 12 wherein R 22 and R 23 are independently alkyl or alkoxy, and R 21 is hydrogen.

24. Compounds according to:

wherein R 1 is an amido which is NR′COR″, and R′ is hydrogen and R″ is alkyl, alkenyl, alkynyl, alkoxy, carbocyclic, heterocylic, aryl, or aralkyl;

wherein X 1 is —O—, —CO—, or —NH—;

wherein X 2 is —O—, —NH—, —CR 19 — or —CO—, wherein R 19 is hydrogen, alkyl, alkenyl, alkynyl;

wherein R 21 is hydrogen, alkyl, alkenyl, alkynyl, or alkoxy;

wherein R 22 is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, aryl, aralkyl, halogen, or nitro;

wherein R 23 is hydrogen, alkyl, alkenyl, alkynyl, aryl, alkoxy or halogen;

wherein X 9 is

wherein X and Y are independently carbon, or nitrogen,

wherein R a , R b , R c , and R d are independently hydrogen, alkyl, or acyl; and wherein one of R a and R b is omitted if X is nitrogen; and wherein one of R c and R d is omitted if Y is nitrogen;

wherein R e and R f are independently hydrogen or hydroxy; and

wherein the dashed line represents an optional double bond.

25. The compounds according to claim 24 wherein R 1 is an amido which is NR′COR″, and R′ is hydrogen and R″ is aryl according to:

wherein R 24 and R 25 are alkoxy.

26. The compounds according to claim 24 wherein X 9 is selected from the group consisting of:

wherein R a , R b , R c , and R d are independently hydrogen, alkyl, or acyl; and

wherein R e and R f are independently hydrogen or hydroxy.

27. The compounds of claim 12 where wherein R 1 is an amido which is —NHCOCH 3 .