Pyrazolo pyridine derivatives as NADPH oxidase inhibitors

• US 9,096,588 B2
• Filed: 09/22/2009
• Issued: 08/04/2015
• Est. Priority Date: 09/23/2008
• Status: Active Grant

• Current Assignee: Calliditas Therapeutics Suisse SA
• Original Assignee: Genkyotex SA (Calliditas Therapeutics AB)
• Inventors: Page, Patrick, Orchard, Mike, Laleu, Benoit, Gaggini, Francesca
• Primary Examiner(s): Pihonak, Sarah
• Application Number:
  US13/120,440
• Publication Number:
  US 20110269757A1
• Time in Patent Office: 2,142 Days
• Field of Search: 514/303, 546/119
• US Class Current: 1/1
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/5025 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/00 : Drugs for skeletal disorders
• CPC Class Codes: A61P 19/10 : for osteoporosis
• CPC Class Codes: A61P 21/00 : Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/00 : Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 27/16 : Otologicals
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention is related to pyrazolo pyridine derivatives of Formula (I), pharmaceutical composition thereof and to their use for the treatment and/or prophylaxis of disorders or conditions related to Nicotinamide adenine dinucleotide phosphate oxidase (NADPH Oxidase).

Claims

1. A pyrazolo pyridine derivative according to Formula (I):

2. The derivative according to claim 1 wherein G₁ is H.

3. The derivative according to claim 1 wherein G₃ is C₁-C₆ alkyl.

4. The derivative according to claim 1 wherein G₃ is a substituted C₁-C₆ alkyl.

5. The derivative according to claim 1 wherein G₄ is —

(CHR³)_m—

(CH₂)_n—

R⁴;

R³, R⁴, m and n are as defined in claim 1.

6. The derivative according to claim 1 wherein R⁴ is —

C(O)R⁷;

R⁷ is as defined in claim 1.

7. The derivative according to claim 1 wherein R⁴ is -A-B;

A and B are as defined in claim 1.

8. The derivative according to claim 1 wherein R⁴ is —

CHR⁸R⁹;

R⁸ and R⁹ are as defined in claim 1.

9. The derivative according to claim 1 wherein R⁴ is —

(CH₂)q-E;

E and q are as defined in claim 1.

10. The derivative according to claim 1 wherein G₅ is H.

12. A pharmaceutical composition containing at least one derivative according to claim 1 and a pharmaceutically acceptable carrier, diluent or excipient thereof.

13. The derivative according to claim 1 wherein G₃ is a substituted aryl.

14. The derivative according to claim 1 wherein R⁴ is —

(CH₂)q-E;

E is NR¹⁴R¹⁵;

R¹⁴, R¹⁵ and q are as defined in claim 1.

15. The derivative according to claim 1 wherein R⁴ is —

(CH₂)q-E;

E is NR¹⁶C(O)—

R¹⁷;

R¹⁶, R¹⁷ and q are as defined in claim 1.

16. The derivative according to claim 1 wherein R⁴ is H.

17. The derivative according to claim 1 wherein G₄ is —

(CHR³)_m—

(CH₂)_n—

R⁴;

R⁴ is —

(CH₂)q-E;

E is optionally substituted C₃-C₈-cycloalkyl;

m is an integer selected from 1 to 5;

n is an integer selected from 1 to 5; and

p and q are integers selected from 0 to 5.

18. The derivative according to claim 1 wherein G₄ is —

(CHR³)_m—

(CH₂)_n—

R⁴;

R⁴ is —

(CH₂)q-E;

E is optionally substituted C₂-C₆ alkynyl;

n is an integer selected from 1 to 5; and

p and q are integers selected from 0 to 5.

19. The derivative according to claim 1, wherein R⁴ is selected from —

C(O)R⁷;

-A-B;

—

CHR⁸R⁹ or —

(CH₂)q-E, and q is an integer selected from 1 to 5.

20. The derivative according to claim 1, wherein E is selected from —

NR¹⁴R¹⁵; and

—

NR¹⁶C(O)—

R¹⁷.

21. The derivative according to claim 1, wherein G₃ is an aryl.

22. The derivative according to claim 4, wherein said substituted C₁-C₆ alkyl is substituted with one to five groups selected from the group consisting of C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈-cycloalkyl, heterocycloalkyl, C₁-C₆ alkyl aryl, C₁-C₆ alkyl heteroaryl, C₁-C₆ alkyl cycloalkyl, C₁-C₆ alkyl heterocycloalkyl, amino, aminosulfonyl, ammonium, acyl amino, amino carbonyl, aryl, heteroaryl, sulfinyl, sulfonyl, alkoxy, alkoxy carbonyl, carbamate, sulfanyl, halogen, trihalomethyl, cyano, hydroxy, mercapto and nitro.

23. The derivative according to claim 13, wherein said substituted aryl is substituted with one to five groups selected from the group consisting of C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈-cycloalkyl, heterocycloalkyl, C₁-C₆ alkyl aryl, C₁-C₆ alkyl heteroaryl, C₁-C₆ alkyl cycloalkyl, C₁-C₆ alkyl heterocycloalkyl, amino, aminosulfonyl, ammonium, acyl amino, amino carbonyl, aryl, heteroaryl, sulfinyl, sulfonyl, alkoxy, alkoxy carbonyl, carbamate, sulfanyl, halogen, trihalomethyl, cyano, hydroxy, mercapto and nitro.

24. The derivative according to claim 1, wherein G₄ is —

(CHR³)_m—

(CH₂)_n—

R⁴, wherein R³ and R⁴ are H, m=0 and n=0-3 and G₅ is selected from H;

optionally substituted C₁-C₆ alkyl;

optionally substituted C₂-C₆ alkenyl;

optionally substituted C₂-C₆ alkynyl;

optionally substituted aryl;

optionally substituted C₁-C₆ alkyl aryl;

optionally substituted aryl C₁-C₆ alkyl;

optionally substituted heteroaryl;

optionally substituted C₁-C₆ alkyl heteroaryl;

optionally substituted heteroaryl C₁-C₆ alkyl;

optionally substituted C₂-C₆ alkenyl aryl;

optionally substituted aryl C₂-C₆ alkenyl;

optionally substituted C₂-C₆ alkenyl heteroaryl;

optionally substituted heteroaryl C₂-C₆ alkenyl;

optionally substituted C₃-C₈-cycloalkyl;

optionally substituted heterocycloalkyl;

optionally substituted C₁-C₆ alkyl C₃-C₈-cycloalkyl;

optionally substituted C₃-C₈-cycloalkyl C₂-C₆ alkyl;

optionally substituted C₁-C₆ alkyl heterocycloalkyl and optionally substituted heterocycloalkyl C₁-C₆ alkyl.

25. The derivative according to claim 1, wherein G₄ is —

(CHR³)_m—

(CH₂)_n—

R⁴, wherein R³ is selected from halogen;

optionally substituted alkoxy;

optionally substituted alkoxy C₁-C₆ alkyl aryl;

optionally substituted C₁-C₆ alkyl aryl;

optionally substituted aryl C₁-C₆ alkyl;

heteroaryl;

optionally substituted C₁-C₆ alkyl heteroaryl;

optionally substituted heteroaryl C₁-C₆ alkyl;

optionally substituted C₃-C₈-cycloalkyl;

optionally substituted C₁-C₆ alkyl C₃-C₈-cycloalkyl;

optionally substituted C₃-C₈-cycloalkyl C₁-C₆ alkyl;

optionally substituted heterocycloalkyl;

optionally substituted C₁-C₆ alkyl heterocycloalkyl; and

optionally substituted heterocycloalkyl C₁-C₆ alkyl;

R⁴ is selected from H;

—

C(O)R⁷;

-A-B;

—

CHR⁸R⁹ and —

(CH₂)q-E;

R⁵ and R⁶ are independently selected from H;

optionally substituted alkoxy C₁-C₆ alkyl;

optionally substituted aryl;

optionally substituted C₁-C₆ alkyl aryl;

optionally substituted aryl C₁-C₆ alkyl;

optionally substituted heteroaryl;

optionally substituted C₁-C₆ alkyl heteroaryl;

optionally substituted heteroaryl C₁-C₆ alkyl;

optionally substituted C₃-C₈-cycloalkyl;

optionally substituted C₁-C₆ alkyl C₃-C₈-cycloalkyl;

optionally substituted C₃-C₈-cycloalkyl C₁-C₆ alkyl;

optionally substituted heterocycloalkyl;

optionally substituted C₁-C₆ alkyl heterocycloalkyl; and

optionally substituted heterocycloalkyl C₁-C₆ alkyl or —

NR⁵R⁶ form together a ring selected from optionally substituted heteroaryl and optionally substituted heterocycloalkyl;

R⁷ is selected from optionally substituted amino;

optionally substituted alkoxy;

optionally substituted aminoalkyl;

optionally substituted alkoxy C₁-C₆ alkyl;

optionally substituted C₁-C₆ alkyl;

optionally substituted C₂-C₆ alkenyl;

optionally substituted C₂-C₆ alkynyl;

—

NR⁵R⁶;

optionally substituted aryl;

optionally substituted C₁-C₆ alkyl aryl;

optionally substituted aryl C₁-C₆ alkyl;

optionally substituted heteroaryl;

optionally substituted C₁-C₆ alkyl heteroaryl;

optionally substituted heteroaryl C₁-C₆ alkyl;

optionally substituted C₃-C₈-cycloalkyl;

optionally substituted C₁-C₆ alkyl C₃-C₈-cycloalkyl;

optionally substituted C₃-C₈-cycloalkyl C₁-C₆ alkyl;

optionally substituted heterocycloalkyl;

optionally substituted C₁-C₆ alkyl heterocycloalkyl; and

optionally substituted heterocycloalkyl C₁-C₆ alkyl;

R⁸ and R⁹ are independently selected from optionally substituted aryl;

optionally substituted heteroaryl;

optionally substituted C₃-C₈-cycloalkyl and optionally substituted heterocycloalkyl;

R¹⁰ is selected from optionally substituted aryl and optionally substituted heteroaryl;

R¹¹ and R¹² are independently selected from H;

optionally substituted acyl;

optionally substituted C₁-C₆ alkyl;

optionally substituted C₂-C₆ alkenyl;

optionally substituted C₂-C₆ alkynyl;

optionally substituted aryl;

optionally substituted C₁-C₆ alkyl aryl;

optionally substituted aryl C₁-C₆ alkyl;

optionally substituted heteroaryl;

optionally substituted C₁-C₆ alkyl heteroaryl;

optionally substituted heteroaryl C₁-C₆ alkyl;

optionally substituted C₃-C₈-cycloalkyl;

optionally substituted C₁-C₆ alkyl C₃-C₈-cycloalkyl;

optionally substituted C₃-C₈-cycloalkyl C₁-C₆ alkyl;

optionally substituted heterocycloalkyl;

optionally substituted C₁-C₆ alkyl heterocycloalkyl; and

optionally substituted heterocycloalkyl C₁-C₆ alkyl or —

NR¹¹R¹² form together a ring selected from optionally substituted heteroaryl and optionally substituted optionally substituted heterocycloalkyl;

R¹³ is selected from optionally substituted aryl;

optionally substituted heteroaryl;

optionally substituted C₃-C₈-cycloalkyl and optionally substituted heterocycloalkyl;

R¹⁴, R¹⁵ and R¹⁶ are independently selected from H and optionally substituted C₁-C₆ alkyl;

R¹⁷ is selected from optionally substituted C₁-C₆ alkyl;

optionally substituted C₂-C₆ alkenyl;

optionally substituted C₂-C₆ alkynyl;

optionally substituted aryl;

optionally substituted C₁-C₆ alkyl aryl;

optionally substituted aryl C₁-C₆ alkyl;

optionally substituted heteroaryl;

optionally substituted C₁-C₆ alkyl heteroaryl;

optionally substituted heteroaryl C₁-C₆ alkyl;

optionally substituted C₃-C₈-cycloalkyl;

optionally substituted C₁-C₆ alkyl C₃-C₈-cycloalkyl;

optionally substituted C₃-C₈-cycloalkyl C₁-C₆ alkyl;

optionally substituted heterocycloalkyl;

optionally substituted C₁-C₆ alkyl heterocycloalkyl; and

optionally substituted heterocycloalkyl C₁-C₆ alkyl;

A is selected from optionally substituted aryl, and optionally substituted heteroaryl;

B is selected from −

OR¹⁰, —

NR¹¹R¹² and a (CH₂)p-R¹³;

E is selected from optionally substituted C₃-C₈-cycloalkyl;

optionally substituted C₂-C₆ alkynyl;

—

NR¹⁴R¹⁵; and

—

NR¹⁶C(O)—

R¹⁷;

m is an integer selected from 1 to 5;

n is an integer selected from 1 to 5;

p and q are integers selected from 0 to 5; and

G₅ is selected from H;

optionally substituted C₁-C₆ alkyl;

optionally substituted C₂-C₆ alkenyl;

optionally substituted C₂-C₆ alkynyl;

optionally substituted aryl;

optionally substituted C₁-C₆ alkyl aryl;

optionally substituted aryl C₁-C₆ alkyl;

optionally substituted heteroaryl;

optionally substituted C₁-C₆ alkyl heteroaryl;

optionally substituted heteroaryl C₁-C₆ alkyl;

optionally substituted C₂-C₆ alkenyl aryl;

optionally substituted aryl C₂-C₆ alkenyl;

optionally substituted C₂-C₆ alkenyl heteroaryl;

optionally substituted heteroaryl C₂-C₆ alkenyl;

optionally substituted C₃-C₈-cycloalkyl;

optionally substituted heterocycloalkyl;

optionally substituted C₁-C₆ alkyl C₃-C₈-cycloalkyl;

optionally substituted C₃-C₈-cycloalkyl C₁-C₆ alkyl;

optionally substituted C₁-C₆ alkyl heterocycloalkyl and optionally substituted heterocycloalkyl C₁-C₆ alkyl.

26. The derivative according to claim 1, wherein G₄ is —

(CHR³)_m—

(CH₂)_n—

R⁴, wherein R³ is selected from H;

halogen;

optionally substituted alkoxy;

optionally substituted alkoxy C₁-C₆ alkyl aryl;

optionally substituted C₁-C₆ alkyl aryl;

optionally substituted aryl C₁-C₆ alkyl;

heteroaryl;

optionally substituted C₁-C₆ alkyl heteroaryl;

optionally substituted heteroaryl C₁-C₆ alkyl;

optionally substituted C₃-C₈-cycloalkyl;

optionally substituted C₁-C₆ alkyl C₃-C₈-cycloalkyl;

optionally substituted C₃-C₈-cycloalkyl C₁-C₆ alkyl;

optionally substituted heterocycloalkyl;

optionally substituted C₁-C₆ alkyl heterocycloalkyl; and

optionally substituted heterocycloalkyl C₁-C₆ alkyl;

R⁴ is selected from —

C(O)R⁷;

-A-B;

—

CHR⁸R⁹ and —

(CH₂)q-E;

R⁷ is selected from optionally substituted amino;

optionally substituted alkoxy;

optionally substituted aminoalkyl;

optionally substituted alkoxy C₁-C₆ alkyl;

optionally substituted C₁-C₆ alkyl;

optionally substituted C₂-C₆ alkenyl;

optionally substituted C₂-C₆ alkynyl;

—

NR⁵R⁶, wherein R⁵ and R⁶ are independently selected from H;

optionally substituted alkoxy C₁-C₆ alkyl;

optionally substituted aryl;

optionally substituted C₁-C₆ alkyl aryl;

optionally substituted aryl C₁-C₆ alkyl;

optionally substituted heteroaryl;

optionally substituted C₁-C₆ alkyl heteroaryl;

optionally substituted heteroaryl C₁-C₆ alkyl;

optionally substituted C₃-C₈-cycloalkyl;

optionally substituted C₁-C₆ alkyl C₃-C₈-cycloalkyl;

optionally substituted C₃-C₈-cycloalkyl C₁-C₆ alkyl;

optionally substituted heterocycloalkyl;

optionally substituted C₁-C₆ alkyl heterocycloalkyl; and

optionally substituted heterocycloalkyl C₁-C₆ alkyl or —

NR⁵R⁶ form together a ring selected from optionally substituted heteroaryl and optionally substituted heterocycloalkyl;

optionally substituted aryl;

optionally substituted aryl;

optionally substituted C₁-C₆ alkyl aryl;

optionally substituted aryl C₁-C₆ alkyl;

optionally substituted heteroaryl;

optionally substituted C₁-C₆ alkyl heteroaryl;

optionally substituted heteroaryl C₁-C₆ alkyl;

optionally substituted C₃-C₈-cycloalkyl;

optionally substituted C₁-C₆ alkyl C₃-C₈-cycloalkyl;

optionally substituted C₃-C₈-cycloalkyl C₁-C₆ alkyl;

optionally substituted heterocycloalkyl;

optionally substituted C₁-C₆ alkyl heterocycloalkyl; and

optionally substituted heterocycloalkyl C₁-C₆ alkyl;

R⁸ and R⁹ are independently selected from optionally substituted aryl;

optionally substituted heteroaryl;

optionally substituted C₃-C₈-cycloalkyl and optionally substituted heterocycloalkyl;

A is selected from optionally substituted aryl, and optionally substituted heteroaryl;

B is selected from —

OR¹⁰, —

NR¹¹R¹² and —

(CH2)p-R¹³;

R¹⁰ is selected from optionally substituted aryl and optionally substituted heteroaryl;

R¹¹ and R¹² are independently selected from H;

optionally substituted acyl;

optionally substituted C₁-C₆ alkyl;

optionally substituted C₂-C₆ alkenyl;

optionally substituted C₂-C₆ alkynyl;

optionally substituted aryl;

optionally substituted C₁-C₆ alkyl aryl;

optionally substituted aryl C₁-C₆ alkyl;

optionally substituted heteroaryl;

optionally substituted C₁-C₆ alkyl heteroaryl;

optionally substituted heteroaryl C₁-C₆ alkyl;

optionally substituted C₃-C₈-cycloalkyl;

optionally substituted C₁-C₆ alkyl C₃-C₈-cycloalkyl;

optionally substituted C₃-C₈-cycloalkyl C₁-C₆ alkyl;

optionally substituted heterocycloalkyl;

optionally substituted C₁-C₆ alkyl heterocycloalkyl; and

optionally substituted heterocycloalkyl C₁-C₆ alkyl or —

NR¹¹R¹² form together a ring selected from optionally substituted heteroaryl and optionally substituted optionally substituted heterocycloalkyl;

R¹³ is selected from optionally substituted aryl;

optionally substituted heteroaryl;

optionally substituted C₃-C₈-cycloalkyl and optionally substituted heterocycloalkyl;

E is selected from optionally substituted C₃-C₈-cycloalkyl;

optionally substituted C₂-C₆ alkynyl;

—

NR¹⁴R¹⁵; and

—

NR¹⁶C(O)—

R¹⁷;

R¹⁴, R¹⁵ and R¹⁶ are independently selected from H and optionally substituted C₁-C₆ alkyl;

R¹⁷ is selected from optionally substituted C₁-C₆ alkyl;

optionally substituted C₂-C₆ alkenyl;

optionally substituted C₂-C₆ alkynyl;

optionally substituted aryl;

optionally substituted C₁-C₆ alkyl aryl;

optionally substituted aryl C₁-C₆ alkyl;

optionally substituted heteroaryl;

optionally substituted C₁-C₆ alkyl heteroaryl;

optionally substituted heteroaryl C₁-C₆ alkyl;

optionally substituted C₃-C₈-cycloalkyl;

optionally substituted C₁-C₆ alkyl C₃-C₈-cycloalkyl;

optionally substituted C₃-C₈-cycloalkyl C₁-C₆alkyl;

optionally substituted heterocycloalkyl;

optionally substituted C₁-C₆ alkyl heterocycloalkyl; and

optionally substituted heterocycloalkyl C₁-C₆ alkyl;

m is an integer selected from 1 to 5;

n is an integer selected from 1 to 5;

p and q are integers selected from 0 to 5; and

G₅ is selected from H;

optionally substituted C₁-C₆ alkyl;

optionally substituted C₂-C₆ alkenyl;

optionally substituted C₂-C₆ alkynyl;

optionally substituted aryl;

optionally substituted C₁-C₆ alkyl aryl;

optionally substituted aryl C₁-C₆ alkyl;

optionally substituted heteroaryl;

optionally substituted C₁-C₆ alkyl heteroaryl;

optionally substituted heteroaryl C₁-C₆ alkyl;

optionally substituted C₂-C₆ alkenyl aryl;

optionally substituted aryl C₂-C₆ alkenyl;

optionally substituted C₂-C₆ alkenyl heteroaryl;

optionally substituted heteroaryl C₂-C₆ alkenyl;

optionally substituted C₃-C₈-cycloalkyl;

optionally substituted heterocycloalkyl;

optionally substituted C₁-C₆ alkyl C₃-C₈-cycloalkyl;

optionally substituted C₃-C₈-cycloalkyl C₁-C₆ alkyl;

optionally substituted C₁-C₆ alkyl heterocycloalkyl and optionally substituted heterocycloalkyl C₁-C₆ alkyl.

11. A pyrazolo pyridine derivative selected from the following compounds:

2-(2-chlorophenyl)-4-methyl-5-(2-morpholin-4-ylbenzyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chlorophenyl)-4-methyl-5-{4-[(4-methylpiperazin-1-yl)methyl]benzyl}-1H-pyrazolo[4,3-c]pyridine-3,6(2H-5H)-dione;

2-(2-chlorophenyl)-4-methyl-5-(2-morpholin-4-yl-2-phenylethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chlorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-fluorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

4-methyl-5-(3-phenoxybenzyl)-2-(4-phenyl-1,3-thiazol-2-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

4,5-dimethyl-2-(4-phenyl-1,3-thiazol-2-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(3-chlorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

N-[2-(2-chlorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-2-(4-fluorophenoxy)acetamide;

2-(2-chlorophenyl)-4-methyl-5-(3-phenoxybenzyl)-1H-pyrazolo[4,3-c]pyridine-3,6 (2H,5H)-dione;

2-(3-chlorophenyl)-4-methyl-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-fluorophenyl)-4-methyl-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyri dine-3,6(2H,5H)-dione;

2-(2-fluorophenyl)-4-methyl-5-[(6-morpholin-4-ylpyridin-2-yl)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-fluorophenyl)-4-methyl-5-[4-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(3-chlorophenyl)-4-methyl-5-[(6-morpholin-4-ylpyridin-2-yl)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

3-(4,5-dimethyl-3,6-dioxo-1,3,5,6-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)benzonitrile;

2-(2-fluorophenyl)-4-methyl-5-(3-phenoxybenzyl)-1H-pyrazolo[4,3-c]pyridine-3,6 (2H,5H)-dione;

2-(3-chlorophenyl)-4-methyl-5-(3-phenoxybenzyl)-1H-pyrazolo[4,3-c]pyridine-3,6 (2H,5H)-dione;

2-(2-chlorophenyl)-4-methyl-5-[(6-morpholin-4-ylpyridin-2-yl)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(3-chlorophenyl)-4-methyl-5-[4-(4-methylpiperazin-1-yl)-4-oxobutyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(3-chlorophenyl)-4-methyl-5-[4-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-[2-(2-fluorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-N-(pyridin-2-ylmethyl)acetamide;

2-(2-chlorophenyl)-4-methyl-5-[4-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chlorophenyl)-4-methyl-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

4-methyl-5-(3-phenoxybenzyl)-2-[1,2,4]triazolo[4,3-b]pyridazin-6-yl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-[4-(benzyloxy)phenyl]-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-[4-(benzyloxy)phenyl]-4-methyl-5-(3-phenoxybenzyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

3-{4-methyl-5-[4-(morpholin-4-ylmethyl)benzyl]-3,6-dioxo-1,3,5,6-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl}benzonitrile;

2-[2-(2-chlorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-N-(pyridin-2-ylmethyl)acetamide;

2-[2-(3-cyanophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-N-(pyridin-2-ylmethyl)acetamide;

2-[2-(3-chlorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-N-(pyridin-2-ylmethyl)acetamide;

2,4-dimethyl-5-(3-phenoxybenzyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chlorophenyl)-5-[3-(diethylamino)propyl]-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chlorophenyl)-5-(cyclohexylmethyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6 (2H,5H) dione;

2-(2-chlorophenyl)-4-methyl-5-[4-(4-methylpiperazin-1-yl)-4-oxobutyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chlorophenyl)-5-(3-phenoxybenzyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(3-chlorophenyl)-4-methyl-5-(3-morpholin-4-yl-3-phenylpropyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(3-chlorophenyl)-4-methyl-5-(3-phenylprop-2-yn-1-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chloro-4-fluorophenyl)-4-methyl-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

4,5-dimethyl-2-{5-[(4-methylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-fluorophenyl)-4-methyl-5-(3-morpholin-4-yl-3-phenylpropyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2,5-dichlorophenyl)-4-methyl-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2,5-dichlorophenyl)-4-methyl-5-(2-morpholin-4-yl-2-oxoethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

N-{2-[2-(2,5-dichlorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]ethyl}acetamide;

2-(2-chloro-4-fluorophenyl)-4-(methoxymethyl)-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chlorophenyl)-5-[2-(dimethylamino)ethyl]-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6 (2H,5H)-dione;

2-[4-(benzyloxy)phenyl]-4-methyl-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(3-chlorophenyl)-4-methyl-5-[2-(4-methylpiperazin-1-yl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(3,4-dichlorophenyl)-4-methyl-5-[4-(4-methylpiperazin-1-yl)-4-oxobutyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

5-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]-2-(2,5-dichlorophenyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chlorophenyl)-4-methyl-5-(3-phenylprop-2-yn-1-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-benzyl-4-methyl-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(3,4-dichlorophenyl)-4-methyl-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chloro-4-fluorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-[4-(benzyloxy)phenyl]-4-methyl-5-(2-morpholin-4-yl-2-oxoethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(3,4-dichlorophenyl)-4-methyl-5-(2-morpholin-4-yl-2-oxoethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

methyl [2-(2,5-dichlorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]acetate;

N-{3-[2-(2,3-dichlorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]phenyl}acetamide;

2-(2,3-dichlorophenyl)-4-methyl-5-[4-(4-methylpiperazin-1-yl)-4-oxobutyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

N-{3-[2-(3-chloro-4-fluorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]phenyl}acetamide;

5-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]-2-(3,4-dichlorophenyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H, 5H)-dione;

2,4-dimethyl-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5 H)-dione;

2,4-dimethyl-5-(3-morpholin-4-yl-3-phenylpropyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H, 5 H)-dione;

N-{3-[2-(2-chloro-4-fluorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]phenyl}acetamide;

2-(2,4-dimethyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)-N-(pyridin-2-ylmethyl)acetamide;

2-(3-chloro-4-fluorophenyl)-4-methyl-5-(2-morpholin-4-yl-2-oxoethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(3-chloro-4-fluorophenyl)-4-methyl-5-[4-(4-methylpiperazin-1-yl)-4-oxobutyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chloro-4-fluorophenyl)-4-methyl-5-(2-morpholin-4-yl-2-oxoethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

5-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]-2-(2-chloro-4-fluorophenyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-[4-(benzyloxy)phenyl]-4-methyl-5-[4-(4-methylpiperazin-1-yl)-4-oxobutyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2,3-dichlorophenyl)-4-methyl-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chloro-4-fluorophenyl)-4-methyl-5-[2-(4-methylpiperazin-1-yl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

N-(3-{[2-(3-chloro-4-fluorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]methyl}phenyl)acetamide;

5-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]-2-(3-chloro-4-fluorophenyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

N-(3-{[2-(2-chloro-4-fluorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]methyl}phenyl)acetamide;

2-(2-chloro-4-fluorophenyl)-4-methyl-5-[4-(4-methylpiperazin-1-yl)-4-oxobutyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

3-{4-methyl-5-[2-(morpholin-4-ylmethyl)benzyl]-3,6-dioxo-1,3,5,6-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl}benzonitrile;

N-{2-[2-(3-chloro-4-fluorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]ethyl}-4-fluorobenzamide;

N-{2-[2-(2-chloro-4-fluorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]ethyl}-4-fluorobenzamide;

2-[2-(2-chloro-4-fluorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-N-(pyridin-2-ylmethyl)acetamide;

N-(2-{2-[4-(benzyloxy)phenyl]-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl}ethyl)-4-fluorobenzamide;

2-(3-chloro-4-fluorophenyl)-4-methyl-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

N-(3-{4-methyl-5-[2-(morpholin-4-ylmethyl)benzyl]-3,6-dioxo-1,3,5,6-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl}phenyl)acetamide;

2-(4-chlorophenyl)-4-methyl-5-(3-phenoxybenzyl)-1H-pyrazolo[4,3-c]pyridine-3,6 (2H,5H)-dione;

2-[2-(3-chloro-4-fluorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-N-(pyridin-2-ylmethyl)acetamide;

2-[4-butyl-2-(3-chloro-4-fluorophenyl)-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-N-(pyridin-2-ylmethyl)acetamide;

2-[2-(2,3-dichlorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyri din-5-yl]-N-(pyridin-2-ylmethyl)acetamide;

2-[2,4-bis(3-chlorophenyl)-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-N-(pyridin-2-ylmethyl)acetamide;

2-[4-(3-chlorophenyl)-2-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-N-(pyridin-2-ylmethyl)acetamide;

N-(3-{[4-(3-chlorophenyl)-2-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]methyl}phenyl)acetamide;

2-(2-chlorophenyl)-4-methyl-5-(2-morpholin-4-yl-2-oxoethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

4-(3-chlorophenyl)-2-methyl-5-(2-morpholin-4-yl-2-oxoethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

4-(4-chlorophenyl)-2-methyl-5-[4-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

4-(3-chlorophenyl)-2-methyl-5-[3-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-[4-(4-chlorophenyl)-2-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-N-(pyridin-2-ylmethyl)acetamide;

4-(3-chlorophenyl)-2-methyl-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

4-(3-chlorophenyl)-2-methyl-5-[4-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

4-(3-chlorophenyl)-2-methyl-5-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chlorophenyl)-4-methyl-5-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

4-(4-chlorophenyl)-2-methyl-5-[2-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

N-(3-{[4-(4-chlorophenyl)-2-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyri din-5-yl]methyl}phenyl)acetamide;

4-(4-chlorophenyl)-2-methyl-5-[3-(morpholin-4-ylmethyl)benzyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

4-(4-chlorophenyl)-2-methyl-5-[(6-morpholin-4-ylpyridin-2-yl)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

N-{2-[4-(4-chlorophenyl)-2-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]ethyl}acetamide;

4-(4-chlorophenyl)-5-[3-(dimethylamino)benzyl]-2-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

4-(4-chlorophenyl)-2-methyl-5-[(6-pyrrolidin-1-ylpyridin-2-yl)methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chlorophenyl)-4-(4-chlorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6 (2H,5H)-dione;

2-(2-chlorophenyl)-4-(2-fluorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyri dine-3,6 (2H,5H)-dione;

2-(2-chlorophenyl)-4-(4-chlorophenyl)-5-[3-(dimethylamino)propyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chlorophenyl)-4-[3-(dimethylamino)phenyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chlorophenyl)-5-methyl-4-(3-morpholin-4-ylphenyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;

2-(2-chlorophenyl)-4-[1-(3,4-difluorophenoxy)ethyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H, 5H)-dione;

4-[1-(benzyloxy)ethyl]-2-(2-chlorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6 (2H,5H)-dione;

or

4-[3-(dimethylamino)phenyl]-2-(2-methoxyphenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione.

27. A pyrazolo pyridine derivative according to Formula (I):