Itraconazole analogs and use thereof

• US 9,346,791 B2
• Filed: 09/07/2012
• Issued: 05/24/2016
• Est. Priority Date: 09/07/2011
• Status: Active Grant

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Liu, Jun O., Shi, Wei, Pasunooti, Kalyan Kumar
• Primary Examiner(s): BERNHARDT, EMILY A
• Application Number:
  US14/343,040
• Publication Number:
  US 20140221393A1
• Time in Patent Office: 1,355 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 405/14 containing three or more hetero rings

Abstract

Provided herein are Itraconazole analogs. Also provided herein are methods of inhibition of Hedgehog pathway, vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, angiogenesis and treatment of disease with Itraconazole analogs.

Claims

1. A compound of structural Formula (IV):

2. The compound of claim 1, wherein:

m is 2; and

each R² is independently chlorine.

3. The compound of claim 2, wherein R¹⁴ is

4. The compound of claim 1, wherein p is 0.

5. The compound of claim 1, wherein A is CR⁶.

6. The compound of claim 5, wherein B is N.

7. The compound of claim 1, wherein A is N.

8. The compound of claim 7, wherein B is CR⁷.

9. The compound of claim 8, wherein R⁷ is hydrogen.

10. The compound of claim 8, wherein p is 0.

11. The compound of claim 8, wherein m is 2.

12. The compound of claim 11, wherein R² is halogen.

13. The compound of claim 8, wherein R⁹ is hydrogen.

14. The compound of claim 13, wherein R⁸ is halogen.

15. A pharmaceutical composition comprising the compound of claim 1 together with a pharmaceutically acceptable carrier.