IP Library › Granted Patent US 9,790,176
Granted Patent B2
US 9,790,176 · App. 14/420,081 · Granted Oct 17, 2017

Compounds for the treatment of mTOR pathway related diseases

Inventors: Mohammad Hossein Pourgholami (Penshurst, AU); David L. Morris (Lugarno, AU); Roger Aston (Kogarah, AU)
Assignee: Pitney Pharmaceuticals Pty Limited
C07C323/62A61K31/277C07C255/29C07C255/62C07C317/44
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 9,790,176
App. No.
14/420,081
Granted
Oct 17, 2017
Kind
B2
Abstract

The present invention relates to compounds for the treatment of mTOR (mammalian Target Of Rapamycin) pathway related diseases. Specifically, the present invention relates to the use of aminoactonitrile derivatives (AADs) in the treatment of mTOR pathway related diseases.

Claims (33)

1. A method for the treatment of one or more mTOR pathway related diseases, the method comprising administering a therapeutically effective amount of a compound of formula (I):

or a pharmaceutically acceptable salt, solvate or prodrug thereof, to a patient in need thereof, wherein

i) R 1 is alkyl, —CF 3 or CN, R 4 is selected from H, alkyl, halogen, alkoxy, —CF 3 , —OCF 3 , —SO 2 —CF 3 , —SO—CF 3 or —S—CF 3 and R 5 is independently selected from H, alkyl, halogen, —CF 3 or —CN; or

ii) R 1 is selected from H or halogen, R 4 is H, halogen, —S—CF 3 , —SOCF 3 or —SO 2 CF 3 , and

R 5 is independently selected from H, halogen, or —CN;

R 2 and R 3 are each independently selected from H, alkyl, halogen, —CF 3 or —CN;

R 6 is independently selected from H, alkyl, halogen, alkoxy, —CF 3 , —OCF 3 , —SO 2 CF 3 , —SOCF 3 or —SCF 3 ;

X is heteroatom, N(alkyl) or NH; and

n is 1 to 20; thereby treating the mTOR pathway related disease, wherein the mTOR pathway related disease is cancer selected from bladder cancer, kidney cancer, liver cancer, lung cancer, esophageal cancer, gall bladder cancer, pancreatic cancer, stomach cancer, thyroid cancer, B-cell lymphoma, T-cell lymphoma, Hodgkins lymphoma, non-Hodgkins lymphoma, hairy cell lymphoma, mantle cell lymphoma, myeloma, Burkett's lymphoma, myelodysplastic syndrome, rhabdomyosarcoma, astrocytoma, neuroblastoma, schwannoma, seminoma, teratocarcinoma, osteosarcoma, or Kaposi's sarcoma.

2. The method of claim 1 , wherein,

R 1 is —CN, H or halogen;

R 2 is H or halogen;

R 3 is —CF 3 or halogen;

R 4 is —SCF 3 , —SOCF 3 , —SO 2 CF 3 , —OCF 3 , or —CF 3 ;

R 5 is H;

R 6 is alkyl;

X is O; and

n is 1 to 5.

3. The method of claim 1 , wherein R 4 is para to the amide moiety.

4. The method of claim 1 , wherein the compound of formula (I) is the (R)- or (S)-enantiomer or the racemate.

5. The method of claim 1 , wherein the compound of formula (I) is the (S)-enantiomer.

6. The method of claim 1 , wherein the compound of formula (I) is selected from any one of the following compounds:

wherein each of the above compounds is the (R)- or (S)-enantiomer, or the racemate, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

7. The method of claim 1 , wherein the compound of formula (I) is

or a pharmaceutically acceptable salt, solvate or prodrug thereof.

8. The method of claim 1 , wherein the compound of formula (I) is MPL (N-[(1S)-1-cyano-2-(5-cyano-2-trifluoromethyl-phenoxy)-1-methyl-ethyl]-4-trifluoromethylsulfanyl-benzamide):

or a pharmaceutically acceptable salt, solvate or prodrug thereof.

9. The method of claim 1 , wherein the compound of formula (I) is monepantel sulphone (MPL-SO 2 ):

or a pharmaceutically acceptable salt, solvate or prodrug thereof.

10. The method according to claim 1 , wherein the cancer is associated with a kinase.

11. The method according to claim 10 , wherein the kinase is a cyclin-dependent kinase.

12. The method according to claim 11 , wherein the cyclin-dependent kinase is cdk2 or cdk4.

13. The method of claim 1 wherein the therapeutically effective amount of a compound of formula (I) is administered in a pharmaceutical composition comprising at least one pharmaceutically acceptable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 27, 2015
From: POURGHOLAMI, MOHAMMAD HOSSEIN; MORRIS, DAVID L.; ASTON, ROGER
To: PITNEY PHARMACEUTICALS PTY LIMITED
Reel/Frame 035506/0250 →
Priority Claims (1)
AU 2012903365 · Aug 6, 2012 · national
Continuity (1)
Related Publication 20150166477A1 · Jun 18, 2015