IP Library › Granted Patent US 9,783,533
Granted Patent B2
US 9,783,533 · App. 14/769,331 · Granted Oct 10, 2017

Glutaminase inhibitors

Inventors: Prashant K. Bhavar (Hyderabad, IN); Swaroop K. Vakkalanka (La Chaux-de-Fonds, CH); Srikant Viswanadha (Hyderabad, IN); Merikapudi Gayatri Swaroop (Hyderabad, IN); Govindarajulu Babu (Hyderabad, IN)
Assignee: RHIZEN PHARMACEUTICALS SA
C07D417/14A61K31/433A61K31/44A61K31/444A61K31/4439A61K31/4545A61K31/497A61K31/4965A61K31/501A61K31/505A61K31/506A61K45/06C07D213/75C07D239/42C07D241/20C07D285/135C07D401/04C07D401/12C07D417/06C07D417/08
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Quick Facts
Patent No.
US 9,783,533
App. No.
14/769,331
Granted
Oct 10, 2017
Kind
B2
Abstract

The present disclosure provides compounds of formula (I) to (III) as glutaminase inhibitors, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of diseases or disorders involving glutamine.

Claims (48)

1. A compound selected from:

2-(Pyridin-2-yl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridin-3-yl) piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide;

(RS)-2-(Pyridin-2-yl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridin-3-yl) piperidin-3-yl)-1,3,4-thiadiazol-2-yl)acetamide;

(R)-2-(Pyridin-2-yl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido) pyridin-3-yl) piperidin-3-yl)-1,3,4-thiadiazol-2-yl)acetamide;

(S)-2-(Pyridin-2-yl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido) pyridin-3-yl) piperidin-3-yl)-1,3,4-thiadiazol-2-yl)acetamide;

(RS)-2-(Pyridin-3-yl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridin-3-yl) piperidin-3-yl)-1,3,4-thiadiazol-2-yl)acetamide;

(R)-2-(Pyridin-3-yl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido) pyridin-3-yl) piperidin-3-yl)-1,3,4-thiadiazol-2-yl)acetamide;

(S)-2-(Pyridin-3-yl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido) pyridin-3-yl) piperidin-3-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(Pyridin-3-yl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridin-3-yl) piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(3-Cyanophenyl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridin-3-yl)piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(Pyridin-2-yl)-N-(5-(4-(5-(2-(3-(trifluoromethoxy)phenyl)acetamido)-1,3,4-thiadiazol-2-yl)piperidin-1-yl)pyridin-2-yl)acetamide;

2-(Pyridin-2-yl)-N-(5-(3-(5-(2-(3-(trifluoromethoxy)phenyl)acetamido)-1,3,4-thiadiazol-2-yl)piperidin-1-yl)pyridin-2-yl)acetamide;

2-(pyridin-2-yl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridazin-3-yl) piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(Pyridin-2-yl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridazin-3-yl)piperidin-3-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(Pyridin-3-yl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridazin-3-yl)piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(3-(Methylsulfonamido)phenyl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl) acetamido)pyridazin-3-yl)piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(2-Chlorophenyl)-N-(6-(4-(5-(2-(pyridin-2-yl)acetamido)-1,3,4-thiadiazol-2-yl) piperidin-1-yl)pyridazin-3-yl)acetamide;

2-(2-Chlorophenyl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridazin-3-yl)piperidin-3-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(2-Fluorophenyl)-N-(6-(4-(5-(2-(pyridin-2-yl)acetamido)-1,3,4-thiadiazol-2-yl) piperidin-1-yl)pyridazin-3-yl)acetamide;

2-(Pyrazin-2-yl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridazin-3-yl)piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(Pyridin-2-yl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridazin-3-yl)piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide dihydrochloride;

2-(Pyridin-2-yl)-N-(6-(4-(5-(2-(3-(trifluoromethoxy)phenyl)acetamido)-1,3,4-thiadiazol-2-yl)piperidin-1-yl)pyridazin-3-yl)acetamide;

2-(Pyridin-3-yl)-N-(6-(4-(5-(2-(3-(trifluoromethoxy)phenyl)acetamido)-1,3,4-thiadiazol-2-yl)piperidin-1-yl)pyridazin-3-yl)acetamide;

2-(Pyridin-3-yl)-N-(6-(4-(5-(2-(2,3,6-trifluorophenyl)acetamido)-1,3,4-thiadiazol-2-yl)piperidin-1-yl)pyridazin-3-yl)acetamide;

2-(Pyridin-2-yl)-N-(6-(4-(5-(2-(2,3,6-trifluorophenyl)acetamido)-1,3,4-thiadiazol-2-yl)piperidin-1-yl)pyridazin-3-yl)acetamide;

2-(2,3-Difluorophenyl)-N-(5-(1-(6-(2-(pyridin-2-yl)acetamido)pyridazin-3-yl)piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(3,4-Difluorophenyl)-N-(5-(1-(6-(2-(pyridin-2-yl)acetamido)pyridazin-3-yl)piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(2-Fluorophenyl)-N-(5-(1-(6-(2-(pyridin-2-yl)acetamido)pyridazin-3-yl)piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(3-Fluorophenyl)-N-(5-(1-(6-(2-(pyridin-2-yl)acetamido)pyridazin-3-yl)piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(4-Fluorophenyl)-N-(5-(1-(6-(2-(pyridin-2-yl)acetamido)pyridazin-3-yl)piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(3-Chlorophenyl)-N-(5-(1-(6-(2-(pyridin-2-yl)acetamido)pyridazin-3-yl)piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide;

3-Hydroxy-2-phenyl-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido) pyridazin-3-yl)piperidin-4-yl)-1,3,4-thiadiazol-2-yl)propanamide;

(R)-2-hydroxy-2-phenyl-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido) pyridazin-3-yl)piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(3-(3-Fluoroazetidin-1-yl)phenyl)-N-(5-(1-(6-(2-(3-(trifluoromethoxy)phenyl) acetamido)pyridazin-3-yl)piperidin-4-yl)-1,3,4-thiadiazol-2-yl)acetamide;

2-(Pyridin-2-yl)-N-(5-((1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridazin-3-yl) piperidin-4-yl)methyl)-1,3,4-thiadiazol-2-yl)acetamide;

and pharmaceutically acceptable salts thereof.

2. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

3. The pharmaceutical composition of claim 2 , further comprising one or more additional therapeutic agents selected from anti-cancer agents, anti-inflammatory agents, immunosuppressive agents, steroids, non-steroidal anti-inflammatory agents, antihistamines, analgesics, and mixtures thereof.

4. A method for the treatment of carcinoma of the kidney, carcinoma of the liver, or carcinoma of the lung, comprising the step of administering to a subject in need thereof an effective amount of compound of claim 1 .

5. The method of claim 4 , further comprising the step of administering simultaneously or sequentially to a subject in need thereof at least one other anti-cancer agent, anti-inflammatory agent, immunosuppressive agent, steroid, non-steroidal anti-inflammatory agent, antihistamine, analgesic, or a mixture thereof.

6. A compound selected from 2-(pyridin-2-yl)-N-(5-((1-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridazin-3-yl)piperidin-4-yl)methyl)-1,3,4-thiadiazol-2-yl)acetamide and pharmaceutically acceptable salts thereof.

7. The method of claim 4 , wherein the subject suffers from carcinoma of the kidney.

8. The method of claim 4 , wherein the subject suffers from carcinoma of the liver.

9. The method of claim 4 , wherein the subject suffers from carcinoma of the lung.

10. A method for the treatment of carcinoma of the kidney, carcinoma of the liver, or carcinoma of the lung, comprising the step of administering to a subject in need thereof an effective amount of compound of claim 6 .

11. The method of claim 10 , wherein the subject suffers from carcinoma of the kidney.

12. The method of claim 10 , wherein the subject suffers from carcinoma of the liver.

13. The method of claim 10 , wherein the subject suffers from carcinoma of the lung.

Assignments (3)
CHANGE OF ADDRESS Recorded Oct 6, 2021
From: RHIZEN PHARMACEUTICALS AG
To: RHIZEN PHARMACEUTICALS AG
Reel/Frame 057836/0286 →
CHANGE OF ADDRESS Recorded Mar 22, 2021
From: RHIZEN PHARMACEUTICALS SA
To: RHIZEN PHARMACEUTICALS SA
Reel/Frame 056775/0375 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 21, 2015
From: BHAVAR, PRASHANT K; VAKKALANKA, SWAROOP K; VISWANADHA, SRIKANT; MERIKAPUDI, GAYATRI S; BABU, GOVINDARAJULU
To: RHIZEN PHARMACEUTICALS SA
Reel/Frame 036846/0642 →
Priority Claims (9)
IN 36/CHE/2014 · Jan 6, 2014 · national
IN 39/CHE/2014 · Jan 6, 2014 · national
IN 2639/CHE/2014 · May 29, 2014 · national
IN 2647/CHE/2014 · May 29, 2014 · national
IN 2783/CHE/2014 · Jun 6, 2014 · national
IN 3525/CHE/2014 · Jul 18, 2014 · national
IN 3612/CHE/2014 · Jul 24, 2014 · national
IN 3613/CHE/2014 · Jul 24, 2014 · national
IN 5438/CHE/2014 · Oct 31, 2014 · national
Continuity (1)
Related Publication 20160318921A1 · Nov 3, 2016