Hedgehog inhibitors

• US 9,174,949 B2
• Filed: 01/06/2011
• Issued: 11/03/2015
• Est. Priority Date: 01/07/2010
• Status: Expired due to Fees

• Current Assignee: Selexagen Therapeutics, Inc.
• Original Assignee: Selexagen Therapeutics, Inc.
• Inventors: Vernier, Jean-Michel, May, John, O'Connor, Patrick, Ripka, William, Pinkerton, Anthony, Bounaud, Pierre-Yves, Hopkins, Stephanie
• Primary Examiner(s): Padmanabhan, Sreeni
• Assistant Examiner(s): Javanmard, Sahar
• Application Number:
  US13/520,150
• Publication Number:
  US 20130012513A1
• Time in Patent Office: 1,762 Days
• Field of Search: 514/366, 514/393, 548/150, 548/302.1
• US Class Current: 1/1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 263/32 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 277/24 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 277/28 Radicals substituted by nitrogen atoms
• CPC Class Codes: C07D 277/30 Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Abstract

Described herein are compounds, pharmaceutical compositions and methods for the inhibition of Hedgehog signaling. Said compounds, pharmaceutical compositions and methods have utility in the treatment of human and veterinary disease and disorders.

Claims

1. A compound having the structure of Formula (I):

2. The compound of claim 1, or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein n is 0.

3. The compound of claim 1, or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein n is 1.

4. The compound of claim 1, or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein R² is halogen.

5. The compound of claim 1, or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein R² is —

CN, -alkyl, or —

CF₃.

6. The compound of claim 1, or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein R² is —

CH₂—

(N-linked heterocycle).

7. The compound of claim 6, or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein the N-linked heterocycle is morpholinyl or piperazinyl.

8. The compound of claim 1, or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein R⁴ is —

SO₂Me or —

OMe.

9. The compound of claim 1, or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein R² is halogen and R⁴ is —

SO₂Me.

10. The compound of claim 1, or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein R² is halogen and R⁴ is —

OMe.

11. The compound of claim 1, or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein n is 0;

G² is H;

G¹ is alkyl;

X is —

S—

;

R² is halogen and R⁴ is —

OMe.

12. The compound of claim 1, or a stereoisomer, tautomer, hydrate, solvate or pharmaceutically acceptable salt thereof, wherein n is 0;

G² is H;

G¹ is alkyl;

X is —

S—

;

R² is halogen and R⁴ is —

SO₂Me.

13. The compound of claim 1, or a hydrate, solvate or pharmaceutically acceptable salt thereof, represented by the structure:

15. A pharmaceutical composition comprising a compound of Formula (I) as described in claim 1, or a stereoisomer, hydrate, solvate or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

16. A pharmaceutical composition comprising the compound as described in claim 13, or a hydrate, solvate or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

14. A compound, or a hydrate, solvate or pharmaceutically acceptable salt thereof, represented by the structure:

17. A pharmaceutical composition comprising a compound as described in claim 14, or a hydrate, solvate or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.