Novobiocin analogues as anticancer agents

• US 7,811,998 B2
• Filed: 10/01/2009
• Issued: 10/12/2010
• Est. Priority Date: 11/03/2004
• Status: Active Grant

• Current Assignee: Secretary of The Department of Health and Human Services, University of Kansas
• Original Assignee: United States Department Of Health And Human Services, University of Kansas
• Inventors: Blagg, Brian S., Neckers, Len, Yu, Xiao Ming
• Primary Examiner(s): Lewis; Patrick T
• Application Number:
  US12/571,899
• Publication Number:
  US 20100048882A1
• Time in Patent Office: 376 Days
• Field of Search: None
• US Class Current: 514/27
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07H 17/075 Benzo[b]pyran-2-ones

Abstract

Novel analogues and derivatives of novobiocin are provided, including compounds having modifications to the amide side chain, coumarin ring, and sugar moieties. The compounds of the present invention are useful as heat shock protein 90 inhibitors, and may be used as anticancer and neuroprotective agents.

Claims

1. A compound according to Formula I

2. The coumarin compound of claim 1 wherein X₁ is —

O— and

X₂ is —

CO—

.

3. The isocoumarin compound of claim 1 wherein X₁ is —

CO— and

X₂ is —

O—

.

4. The compound of claim 2 wherein R⁴ and R⁵ are both methyl.

5. The compound of claim 2 wherein X₄ is —

CR²⁰— and

R²⁰ is hydrogen, and wherein X₈ is —

CR²³— and

R²³ is hydrogen or alkyl.

6. The compound of claim 5 wherein R¹ is amido.

7. The compound of claim 6 selected from the group consisting of:

8. The compound of claim 5 wherein R¹ is hydrogen.

9. The compound of claim 8 selected from the group consisting of:

10. The compound of claim 2 wherein X₄, is —

CR²⁰— and

R²⁰ is alkyl and wherein R¹ is aryl.

11. The compound of claim 10 selected from the group consisting of:

12. The compound of claim 2 wherein X₄ is —

CR²⁰— and

R²⁰ is hydrogen, and wherein X₈ is —

CR²³— and

R²³ is alkyl.

13. The compound of claim 12 wherein R¹ is amido.

14. The compound of claim 13 selected from the group consisting of:

15. A compound according to Formula II:

16. The compound of claim 15 selected from the group consisting of:

17. A compound according to Formula III:

18. The compound of claim 17 selected from the group consisting of: