ITRACONAZOLE ANALOGS AND USE THEREOF

• US 20160264556A1
• Filed: 05/23/2016
• Published: 09/15/2016
• Est. Priority Date: 09/07/2011
• Status: Abandoned Application

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Liu, Jun O., Shi, Wei, Pasunooti, Kalyan Kumar
• Application Number:
  US15/162,524
• Publication Number:
  US 20160264556A1
• Time in Patent Office: Days
• 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 (I):

2. The compound of claim 1, wherein:

X and Z are N;

Y is CH;

A is CR⁶;

B is CR⁷;

W is CR⁸;

V is CR⁹;

D is

3. The compound of claim 2, wherein the compound is of structural Formula (II):

4. The compound of claim 3, wherein Q is CH₂.

5. The compound of claim 4, wherein T is hydrogen.

6. The compound of claim 4, wherein:

T is OR¹¹; and

R¹¹ is hydrogen.

7. The compound of claim 3, wherein Q is O.

8. The compound of claim 7, wherein T is hydrogen.

9. The compound of claim 7, wherein:

T is OR11; and

R11 is hydrogen.

10. The compound of claim 2, wherein the compound is of structural Formula (III):

11. The compound of claim 1, wherein the compound is of structural Formula (IV):

12. The compound of claim 11, wherein:

m is 2; and

each R² is independently chlorine.

13. The compound of claim 12, wherein R¹⁴ is

14. The compound of claim 13, wherein:

W is CR8; and

V is CR9.

15. The compound of claim 14, wherein p is 0.

16. The compound of claim 15, wherein:

each R4 is independently alkyl; and

q is 0, 1, or 2.

17. The compound of claim 16, wherein:

each R5 is independently halogen; and

t is 0, 1, or 2.

18. The compound of claim 17, wherein A is CR⁶.

19. The compound of claim 18, wherein B is CR⁷.

20. The compound of claim 18, wherein B is N.