COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR

• US 20110059963A1
• Filed: 10/18/2010
• Published: 03/10/2011
• Est. Priority Date: 06/22/2005
• Status: Active Grant

• Current Assignee: Plexxikon Inc (Daiichi Sankyo Company Limited)
• Original Assignee: Plexxikon Inc (Daiichi Sankyo Company Limited)
• Inventors: Tsai, James, Artis, Dean R., Spevak, Wayne, Zhang, Jiazhong, Bollag, Gideon, Hirth, Klaus-Peter, Shi, Shenghua, Zhang, Chao, Mamo, Shumeye, Ibrahim, Prabha N., Bremer, Ryan, Gillette, Samuel J., Cho, Hanna
• Granted Patent: US 8,470,818 B2
• Time in Patent Office: Days
• US Class Current: 514/234.5
• 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 31/5377 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 1/04 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 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• 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 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/14 : for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• 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 27/02 : 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 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 3/14 : for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• 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 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• 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 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• 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: C07C 37/62 : by introduction of halogen; by substitution of halogen atoms by other halogen atoms
• CPC Class Codes: C07C 39/27 : all halogen atoms being bound to ring carbon atoms
• CPC Class Codes: C07C 45/00 : Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
• CPC Class Codes: C07C 45/673 : by change of size of the carbon skeleton
• CPC Class Codes: C07C 45/71 : being hydroxy groups
• CPC Class Codes: C07C 47/565 : all hydroxy groups bound to the ring
• CPC Class Codes: C07C 47/575 : containing ether groups, groups, groups, or groups
• CPC Class Codes: C07D 209/08 : with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems

Abstract

Compounds active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases.

Claims

1. A method for treating a subject suffering from or at risk of a protein kinase mediated disease or condition, said method comprising administering to said subject a compound effective for the treatment of a protein kinase mediated disease or condition, said compound having the structure of Formula IIIm:

2. The method according to claim 1 wherein said protein kinase is selected from the group consisting of B-Raf, any mutation of B-Raf, c-Raf-1, and any mutation of c-Raf-1.

3. The method according to claim 2 wherein said disease or condition is selected from the group consisting of ischemic stroke, multi-infarct dementia, head injury, spinal cord injury, Alzheimer'"'"'s disease, Parkinson'"'"'s disease, acute myeloid leukemia, melanoma, gliomas, sarcomas, histiocytic lymphoma, neurofibromatosis, myelodysplastic syndrome, tumor angiogenesis, thyroid cancer, liver cancer, colorectal cancer, pancreatic cancer, breast cancer, ovarian cancer, lung cancer, acute pain, chronic pain, migraine, heart failure, cardiac hypertrophy, thrombosis, atherosclerosis, reperfusion injury, polycystic kidney disease, rheumatoid arthritis, inflammatory bowel disease, psoriasis, osteoarthritis, endometriosis, scarring, vascular restenosis, fibrotic disorders, immunodeficiency diseases, organ transplant rejection, graft versus host disease, diabetic nephropathy, nephrosclerosis, glomerulonephritis, prostate hyperplasia, metabolic syndrome, obesity, Helicobacter pylori infection, Influenza virus infection, fever, sepsis, chronic obstructive pulmonary disease, acute respiratory distress syndrome. Noonan'"'"'s syndrome, Costello syndrome, leopard syndrome, cardio-faciocutaneous syndrome, and neural crest syndrome abnormalities causing cardiovascular, skeletal, intestinal, skin, hair or endocrine diseases.

4. The method according to claim 2 wherein said disease or condition is selected from the group consisting of ischemic stroke, multi-infarct dementia, head injury, spinal cord injury, Alzheimer'"'"'s disease, Parkinson'"'"'s disease, acute myeloid leukemia, melanoma, gliomas, sarcomas, histiocytic lymphoma, neurofibromatosis, myelodysplastic syndrome, tumor angiogenesis, thyroid cancer, liver cancer, colorectal cancer, pancreatic cancer, breast cancer. ovarian cancer, lung cancer, prostate hyperplasia, acute pain, chronic pain, migraine, and polycystic kidney disease.

5. The method according to claim 2 wherein said disease or condition is selected from the group consisting of melanoma, thyroid cancer, liver cancer, colorectal cancer, breast cancer, ovarian cancer, lung cancer, and prostate hyperplasia.

6. The method according to claim 2 wherein said disease or condition is melanoma, thyroid cancer or colorectal cancer.

7. The method according to claim 2 wherein said protein kinase is a mutant of B-Raf.

8. The method according to claim 7 wherein said protein kinase is a V600E mutant of B-Raf.

9. The method according to claim 7 wherein said disease or condition is melanoma.

10. The method according to claim 7 wherein said disease or condition is thyroid cancer.

11. The method according to claim 7 wherein said disease or condition is colorectal cancer.

12. The method of claim 1, wherein said compound having the structure of Formula IIIm is further defined as follows:

R⁸¹ is selected from the group consisting of hydrogen, halogen, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, —

CN, —

S(O)₂NH₂, —

C(O)NH₂, —

OR⁶⁸, —

SR⁶⁸, —

NR⁶⁹R⁶⁸, —

C(O)R⁶⁸, —

C(S)R⁶⁸, —

C(O)NR⁶⁹R⁶⁸, —

S(O)₂NR⁶⁹R⁶⁸, —

NR⁶⁹C(O)R⁶⁸, —

NR⁶⁹S(O)₂R⁶⁸, —

S(O)R⁶⁸, and —

S(O)₂R⁶⁸.

13. The method of claim 1, wherein said compound having the structure of Formula IIIm is further defined as follows:

lower alkyl as R⁶⁸, R⁶⁹, R⁷⁹, R⁸⁰, or R⁸¹, C_2-6 alkyl as R¹¹², lower alkenyl as R⁶⁸ or R⁸¹, or lower alkenyl as R⁶⁸ or R⁸¹ are optionally substituted with 1, 2, or 3 substituents selected from the group consisting of fluoro, —

NO₂, —

CN, —

OR^1a, —

SR^1a, —

NR^1aR^1a, —

OC(O)R^1a, —

OC(S)R^1a, —

C(O)R^1a, —

C(S)R^1a, —

C(O)OR^1a, —

C(S)OR^1a, —

C(O)NR^1aR^1a, —

C(S)NR^1aR^1a, —

S(O)₂NR^1aR^1a, —

C(NH)NR^1aR^1a, —

NR^1aC(O)R^1a, —

NR^1aC(S)R^1a, —

NR^1aS(O)₂R^1a, —

NR^1aC(O)NR^1aR^1a, —

NR^1aC(S)NR^1aR^1a, —

NR^1aS(O)₂NR^1aR^1a, —

S(O)R^1a, —

S(O)₂R^1a, cycloalkyl, heterocycloalkyl, aryl and heteroaryl;

cycloalkyl, heterocycloalkyl, aryl or heteroayl, as R⁶⁸, R⁸¹, R¹¹², or a substituent of lower alkyl, lower alkenyl or lower alkynyl are optionally substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, —

NO₂, —

CN, —

OR^1a, —

SR^1a, —

NR^1aR^1a, —

OC(O)R^1a, —

OC(S)R^1a, —

C(O)R^1a, —

C(S)R^1a, —

C(O)OR^1a, —

C(S)OR^1a, —

C(O)NR^1aR^1a, —

C(S)NR^1aR^1a, —

S(O)₂NR^1aR^1a, —

C(NH)NR^1aR^1a, —

NR^1aC(O)R¹a, —

NR^1aC(S)R^1a, —

NR^1aS(O)₂R^1a, —

NR^1aC(O)NR^1aR^1a, —

NR^1aC(S)NR^1aR^1a, —

NR^1aS(O)₂NR^1aR^1a, —

S(O)R^1a, —

S(O)₂R^1a, —

R^1b, and lower alkyl, wherein lower alkyl is optionally substituted with 1, 2 or 3 substituents selected from the group consisting of fluoro, —

OH, —

NH₂, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, fluoro substituted lower alkylthio, mono-alkylamino, di-alkylamino, and —

R^1b;

R^1a is selected from the group consisting of hydrogen, —

R^1b, and lower alkyl, provided, however, that hydrogen is not bound to any of C(S), C(O), S(O), or S(O)₂ of —

OC(O)R^1a, —

OC(S)R^1a, —

C(O)R^1a, —

C(S)R^1a, —

NR^1aC(O)R^1a, —

NR^1aC(S)R^1a, —

NR^1aS(O)₂R^1a, —

S(O)R^1a, or —

S(O)₂R^1a, wherein lower alkyl is optionally substituted with 1, 2 or 3 substituents selected from the group consisting of fluoro, —

OH, —

NH₂, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, fluoro substituted lower alkylthio, mono-alkylamino, di-alkylamino, and —

R^1b, provided, however, that any substitution of the alkyl carbon bound to O, S, or N of —

OR^1a, —

SR^1a, —

NR^1aR^1a, —

C(O)OR^1a, —

C(S)OR^1a, —

C(O)NR^1aR^1a, —

C(S)NR^1aR^1a, —

S(O)₂NR^1aR^1a, —

C(NH)NR^1aR^1a, —

NR^1aC(O)R^1a, —

NR^1aC(S)R^1a, —

NR^1aS(O)₂R^1a, —

NR^1aC(O)NR^1aR^1a, —

NR^1aC(S)NR^1aR^1a, or —

NR^1aS(O)₂NR^1aR^1a, is fluoro or —

R^1b; and

R^1b is selected from the group consisting of cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with 1, 2 or 3 substituents selected from the group consisting of halogen, —

CN, —

OH, —

NH₂, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, fluoro substituted lower alkylthio, mono-alkylamino, di-alkylamino, and cycloalkylamino.

14. The method of claim 1. wherein said compound having the structure of Formula IIIm is further defined as follows:

lower alkyl as R⁶⁸, R⁶⁹, R⁷⁹, R⁸⁰, or R⁸¹, C_2-6 alkyl as R¹¹², lower alkenyl as R⁶⁸ or R⁸¹, or lower alkynyl as R⁶⁸ or R⁸¹ are optionally substituted with 1, 2, or 3 subtituents selected from the group consisting of fluoro, —

CN, —

OR^1a, —

SR^1a, —

NR^1aR^1a, —

C(O)R^1a, —

C(S)R^1a, —

C(O)OR^1a, —

C(O)NR^1aR^1a, —

C(S)NR^1aR^1a, —

S(O)₂NR^1aR^1a, —

NR^1aC(O)R^1a, —

NR^1aC(S)R^1a, —

NR^1aS(O)₂R^1a, —

S(O)R^1a, —

S(O)₂R^1a, cycloalkyl, heterocycloalkyl, aryl and heteroaryl; and

cycloalkyl, heterocycloalkyl, aryl or heteroayl, as R⁶⁸, R⁸¹, R¹¹², or a substituent of lower alkyl, lower alkenyl or lower alkynyl are optionally substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, —

CN, —

OR^1a, —

SR^1a, —

NR^1aR^1a, —

C(O)R^1a, —

C(S)R^1a, —

C(O)OR^1a, —

C(O)NR^1aR^1a, —

C(S)NR^1aR^1a, —

S(O)₂NR^1aR^1a, —

NR^1aC(O)R^1a, —

NR^1aC(S)R^1a, —

NR^1aS(O)₂R^1a, —

S(O)R^1a, —

S(O)₂R^1a, —

R^1b, and lower alkyl, wherein lower alkyl is optionally substituted with 1, 2 or 3 substituents selected from the group consisting of fluoro, —

OH, —

NH₂, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, fluoro substituted lower alkylthio, mono-alkylamino, di-alkylamino, and —

R^1b.

15. The method of claim 14, wherein R¹¹² of said compound having the structure of Formula IIIm is optionally substituted C_2-6 alkyl.

16. The method of claim 14, wherein R¹¹² of said compound having the structure of Formula IIIm is —

NR⁷⁹R⁸⁰.

17. The method of claim 14, wherein R¹¹² of said compound having the structure of Formula IIIm is optionally substituted aryl.

18. The method of claim 14, wherein R¹¹² of said compound having the structure of Formula IIIm is optionally substituted heteroaryl.

19. The method of claim 1, wherein said compound having the structure of Formula IIIm is further defined as follows:

R⁸¹ is selected from the group consisting of hydrogen;

halogen;

C_1-6 alkyl optionally substituted with carboxylic acid;

C_2-6 alkenyl optionally substituted with carboxylic acid;

C_1-6 alkoxy optionally substituted with methoxy or diethylamine;

carboxylic acid;

carboxylic acid methyl ester;

carboxylic acid ethylamide;

4-methyl-piperidin-1-yl;

4-methyl-piperazin-1-yl;

morpholin-4-yl;

phenyl-amino;

phenyl optionally substituted with halogen, —

CN, optionally fluoro substituted C_1-6 alkyl, dimethylamine, methoxy, carboxylic acid, carboxylic acid amide, carboxylic acid-dimethyl amide, morpholine-4-carbonyl, morpholine, morpholine-4-methyl, or 2-methoxy-ethoxy;

pyridinyl optionally substituted with methoxy, morpholine, or 4-methyl-piperazin-1-yl;

4-methyl-1H-imidazol-2-yl; and

N-methyl-pyrazolyl;

R⁸³ is selected from the group consisting of hydrogen, fluoro and chloro;

R¹¹² is selected from the group consisting of C_2-6 alkyl;

phenyl optionally substituted with —

CN, —

NO₂, acetamide, halogen, optionally fluoro substituted C_1-6 alkyl, optionally fluoro substituted C_1-6 alkoxy, or oxazolyl;

2,3-dihydro-benzo[1,4]dioxin-6-yl;

methyl substituted thiazole, methyl substituted imidazole, thiophene optionally substituted with methyl, oxazole, isoxazole, or pyridine;

furan substituted with methyl or carboxylic acid methyl ester;

benzothiazol-6-yl;

benzo[b]thiophen-2-yl;

piperidin-1-yl; and

dimethylamine.

20. The method of claim 19, wherein R¹¹² of said compound having the structure of Formula IIIm is C_2-6 alkyl.

21. The method of claim 19, wherein R¹¹² of said compound having the structure of Formula IIIm is piperidin-1-yl or dimethylamine.

22. The method of claim 19, wherein R¹¹² of said compound having the structure of Formula IIIm is selected from the group consisting of 2,3-dihydro-benzo[1,4]dioxin-6-yl;

and phenyl optionally substituted with —

CN, —

NO₂, acetamide, halogen, optionally fluoro substituted C_1-6 alkyl, optionally fluoro substituted C_1-6 alkoxy, or oxazolyl.

23. The method of claim 19, wherein R¹¹² of said compound having the structure of Formula IIIm is selected from the group consisting of methyl substituted thiazole;

methyl substituted imidazole;

thiophene optionally substituted with methyl, oxazole, isoxazole, or pyridine;

furan substituted with methyl or carboxylic acid methyl ester;

benzothiazol-6-yl; and

benzo[b]thiophen-2-yl.

24. The method of claim 1, wherein said compound having the structure of Formula IIIm is selected from the group consisting of:

Propane-1-sulfonic acid [2,4-difluoro-3-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

Propane-1-sulfonic acid [3-(5-ethoxy-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]amide,

Propane-1-sulfonic acid [2-fluoro-3-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]amide,

Propane-1-sulfonic acid {3-[5-(2-diethylamino-ethoxy)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide,

Butane-1-sulfonic acid [2,4-difluoro-3-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide, and

any pharmaceutically acceptable salts thereof.

25. The method of claim 1, wherein said compound having the structure of Formula IIIm is selected from the group consisting of:

Propane-1-sulfonic acid [2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide, Propane-1-sulfonic acid [2,4-difluoro-3-(5-isopropenyl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

Propane-1-sulfonic acid [2,4-difluoro-3-(5-isopropyl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

Propane-1-sulfonic acid [2,4-difluoro-3-(5-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

Propane-1-sulfonic acid [4-chloro-2-fluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide.

Propane-1-sulfonic acid [2-fluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

3-3-[2,6-Difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl-acrylic acid,

3-3-[2,6-Difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl-propionic acid,

Butane-1-sulfonic acid [3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-pheny]-amide,

Propane-1-sulfonic acid [2,4-difluoro-3-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

Propane-1-sulfonic acid [4-chloro-3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2-fluoro-phenyl]-amide, and

any pharmaceutically acceptable salts thereof.

26. The method of claim 1, wherein said compound having the structure of Formula him is selected from the group consisting of:

3-[2,6-Difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid methyl ester,

3-[2,6-Difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid,

3-[2,6-Difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid ethylamide, and

any pharmaceutically acceptable salts thereof.

27. The method of claim 1, wherein said compound having the structure of Formula IIIm is selected from the group consisting of:

Propane-1-sulfonic acid [4-chloro-2-fluoro-3-(5-phenyl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

Propane-1-sulfonic acid [2,4-difluoro-3-(5-phenyl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

Propane-1-sulfonic acid {3-[5-(4-dimethylamino-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide,

Propane-1-sulfonic acid {2,4-difluoro-3-[5-(4-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide,

Propane-1-sulfonic acid {2,4-difluoro-3-[5-(3-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide,

Propane-1-sulfonic acid {3-[5-(3-dimethylamino-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide,

Propane-1-sulfonic acid [2-fluoro-3-(5-phenyl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

Propane-1-sulfonic acid {2,4-difluoro-3-[5-(3-fluoro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide,

Propane-1-sulfonic acid {2,4-difluoro-3-[5-(4-fluoro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide,

Propane-1-sulfonic acid {3-[5-(3-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide,

3-{3-[2,6-Difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-benzoic acid.

4-{3-[2,6-Difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-benzamide,

4-{3-[2,6-Difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-N,N-dimethyl-benzamide,

Propane-1-sulfonic acid (2,4-difluoro-3-{5-[4-(morpholine-4-carbonyl)-phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carbonyl}-phenyl)-amide,

Propane-1-sulfonic acid {2,4-difluoro-3-[5-(3-morpholin-4-yl-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide,

Propane-1-sulfonic acid {2,4-difluoro-3-[5-(3-morpholin-4-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide,

Propane-1-sulfonic acid {3-[5-(4-cyano-3,5-dimethyl-phenyl)-1H-pyrrolo[2,3-11 pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide,

3-{3-[2,6-difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-benzamide,

Propane-1-sulfonic acid (2,4-difluoro-3-{5-[4-(2-methoxy-ethoxy)-phenyl]-1H-pyrrolo[2,3-b]-pyridine-3-carbonyl}-phenyl)-amide,

4-{3-[2,6-Difluoro-3-(propane-1-sulfonylamino)-benzoyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-2,N,N-trimethyl-benzamide, and

any pharmaceutically acceptable salts thereof.

28. The method of claim 1, wherein said compound having the structure of Formula IIIm is selected from the group consisting of:

Propane-2-sulfonic acid [2,4-difluoro-3-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carbonye-phenyl]-amide,

Propane-1-sulfonic acid [2-fluoro-3-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

Propane-1-sulfonic acid [2,4-difluoro-3-(5-pyridin-4-yl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

Propane-1-sulfonic acid {2,4-difluoro-3-[5-(6-methoxy-pyridin-3-yl)-1H-pyrrolo[2, 3-b]pyridine-3-carbonyl]-phenyl}-amide,

Propane-1-sulfonic acid {2,4-difluoro-3-[5-(6-morpholin-4-yl-pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide,

Propane-1-sulfonic acid (2,4-difluoro-3-{5-[6-(4-methyl-piperazin-1-yl)-pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridine-3-carbonyl}-phenyl)-amide,

Propane-1-sulfonic acid {2,4-difluoro-3-[5-(4-methyl-1H-imidazol-2-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide,

Propane-1-sulfonic acid {2,4-difluoro-3-[5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide, and

any pharmaceutically acceptable salts thereof.

29. The method of claim 1, wherein said compound having the structure of Formula IIIm is selected from the group consisting of:

Propane-1-sulfonic acid [2,4-difluoro-3-(5-phenylamino-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

Propane-1-sulfonic acid {2,4-difluoro-3-[5-(4-methyl-piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide,

Propane-1-sulfonic acid {2,4-difluoro-3-[5-(4-methyl-piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide, and

any pharmaceutically acceptable salts thereof.

30. The method of claim 1, wherein said compound having the structure of Formula IIIm is selected from the group consisting of:

Dimethylamine-1-sulfonic acid [3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide,

Dimethylamine-1-sulfonic acid [3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide,

Dimethylamine-1-sulfonic acid [3-(5-phenyl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide,

Piperidine-1-sulfonic acid [2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

Piperidine-1-sulfonic acid [3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide,

Dimethylamine-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3carbonyl]-2,4-difluoro-phenyl}-amide, and

any pharmaceutically acceptable salts thereof.

31. The method of claim 1, wherein said compound having the structure of Formula IIIm is selected from the group consisting of:

N-{3-[5-(4-Chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-4-trifluoromethyl-benzenesulfonamide,

N-[3-(5-Ethyl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-4-trifluoromethyl-benzenesulfonamide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-3-fluoro-4-methyl-benzenesulfonamide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-4-methyl-benzenesulfonamide,

N-(2,4-Difluoro-3-{5-[4-(2-methoxy-ethoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carbonyl}-phenyl)-4-trifluoromethyl-benzenesulfonamide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-benzenesulfonamide,

N-[2,4-Difluoro-3-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-benzenesulfonamide,

N-{2,4-difluoro-3-[5-(2-methoxy-ethoxy)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-4-trifluoromethyl-benzenesulfonamide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-2-methyl-benzenesulfonamide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-5-fluoro-2-methyl-benzenesulfonamide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-3-methyl-benzenesulfonamide,

N-[2,4-Difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-2-methyl-benzenesulfonamide,

N-[2,4-Difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-3-methyl-benzenesulfonamide.

N-[2,4-Difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-4-isopropyl-benzenesulfonamide,

N-[2,4-Difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-benzenesulfonamide,

N-[2,4-Difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-5-fluoro-2-methyl-benzenesulfonamide.

N-[2,4-Difluoro-3-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-benzenesulfonamide,

N-{2,4-Difluoro-3-[5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-4-trifluoromethyl-benzenesulfonamide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2-fluoro-phenyl]benzenesulfonamide,

N-[2,4-Difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-4-trifluoromethyl-benzenesulfonamide, and

any pharmaceutically acceptable salts thereof.

32. The method of claim 1, wherein said compound having the structure of Formula IIIm is selected from the group consisting of:

N-[2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)phenyl]-3-methoxy-benzenesulfonamide,

N-[2,4-Difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-4-methoxy-benzenesulfonamide,

4-Butoxy-N-[2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-benzenesulfonamide,

N-[2,4-Difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-3,4-dimethoxy-benzenesulfonamide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-4-methoxy-benzenesulfonamide,

N-[3-(5-Chloro-1H-pyrro lo [2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-3-methoxy-benzenesulfonamide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-2,4-dimethoxy-benzenesulfonamide,

2,3-Dihydro-benzo[1,4]dioxine-6-sulfonic acid [3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-2,5-dimethoxy-benzenesulfonamide.

N-[2,4-Difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-2,4-dimethoxy-benzenesulfonamide,

2,3-Dihydro-benzo[1,4]dioxine-6-sulfonic acid [2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-4-difluoromethoxy-benzenesulfonamide, and

any pharmaceutically acceptable salts thereof.

33. The method of claim 1, wherein said compound having the structure of Formula IIIm is selected from the group consisting of:

4-Chloro-N-[2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-benzenesulfonamide,

3,4-Dichloro-N-[2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-benzenesulfonamide,

N-[2,4-Difluoro-3-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-3-fluoro-benzenesulfonamide,

N-[2,4-Difluoro-3-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-4-fluoro-benzenesulfonamide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-3-fluoro-benzenesulfonamide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-4-fluoro-benzenesulfonamide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-3,5-difluoro-benzenesulfonamide,

N-[2,4-Difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-4-fluoro-benzenesulfonamide,

N-{2,4-Difluoro-3-[5-(2-methoxy-ethoxy)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-4-fluoro-benzenesulfonamide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-2-fluoro-benzenesulfonamide, and

any pharmaceutically acceptable salts thereof.

34. The method of claim 1, wherein said compound having the structure of Formula IIIm is selected from the group consisting of:

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-4-cyano-benzenesulfonamide,

N-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-4-oxazol-5-yl-benzenesulfonamide,

N-[2,4-Difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-4-oxazol-5-yl-benzenesulfonamide,

N-{4-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenylsulfamoyl]-phenyl}-acetamide,

N-[2,4-Difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-3-nitro-benzenesulfonamide,

N-{4-[2,4-Difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenylsulfamoyl]-phenyl}-acetamide,

2-Cyano-N-[2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-benzenesulfonamide,

3-Cyano-N-[2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-benzene sulfonamide, and

any pharmaceutically acceptable salts thereof.

35. The method of claim 1, wherein said compound having the structure of Formula IIIm is selected from the group consisting of:

Thiophene-3-sulfonic acid [3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide,

Benzo[b]thiophene-2-sulfonic acid [3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide,

5-Pyridin-2-yl-thiophene-2-sulfonic acid [3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide,

Thiophene-2-sulfonic acid [3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide,

2,5-Dimethyl-thiophene-3-sulfonic acid [3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide,

5-Isoxazol-5-yl-thiophene-2-sulfonic acid [2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

2,5-Dimethyl-thiophene-3-sulfonic acid [2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

2,4-Dimethyl-thiazole-5-sulfonic acid [2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

Benzothiazole-6-sulfonic acid [2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

2,4-Dimethyl-thiazole-5-sulfonic acid [3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide,

5-Oxazol-5-yl-thiophene-2-sulfonic acid [2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide,

1,2-Dimethyl-1H-imidazole-4-sulfonic acid [3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide,

5-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenylsulfamoyl]-furan-2-carboxylic acid methyl ester,

5-[3-(5-Chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenylsulfamoyl]-2-methyl-furan-3-carboxylic acid methyl ester,

2,5-Dimethyl-furan-3-sulfonic acid [3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide,

5-[2,4-Difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenylsulfamoyl]-furan-2-carboxylic acid methyl ester,

5-[2,4-Difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenylsulfamoyl]-2-methyl-furan-3-carboxylic acid methyl ester,

2,5-Dimethyl-furan-3-sulfonic acid [2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide, and

any pharmaceutically acceptable salts thereof.

36. The method of claim 1, wherein said compound having the structure of Formula IIIm is N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-2,4-difluoro-benzenesulfonamide and any pharmaceutically acceptable salts thereof.

37. The method of claim 1, wherein said compound having the structure of Formula IIIm is N-[2,4-difluoro-3-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-3-trifluoromethyl-benzenesulfonamide and any pharmaceutically acceptable salts thereof.

38. The method of claim 1, wherein said compound having the structure of Formula IIIm is N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-3-trifluoromethyl-benzenesulfonamide and any pharmaceutically acceptable salts thereof.

39. The method of claim 1, wherein said compound having the structure of Formula IIIm is N-[2,4-difluoro-3-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-4-trifluoromethyl-benzenesulfonamide and any pharmaceutically acceptable salts thereof.

40. The method of claim 1, wherein said compound having the structure of Formula IIIm is N-{2,4-difluoro-3-[5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-3-fluoro-benzenesulfonamide and any pharmaceutically acceptable salts thereof.

41. The method of claim 1, wherein said compound having the structure of Formula IIIm is N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-2-cyano-benzenesulfonamide and any pharmaceutically acceptable salts thereof.

42. The method of claim 1, wherein said compound having the structure of Formula IIIm is N-{2,4-difluoro-3-[5-(6-methoxy-pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-3-fluoro-benzenesulfonamide and any pharmaceutically acceptable salts thereof.

43. The method of claim 1, wherein said compound having the structure of Formula IIIm is N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-4-trifluoromethyl-benzenesulfonamide and any pharmaceutically acceptable salts thereof.

44. The method of claim 1, wherein said compound having the structure of Formula IIIm is N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-3-cyano-benzenesulfonamide and any pharmaceutically acceptable salts thereof.

45. The method of claim 1, wherein said compound having the structure of Formula IIIm is N-{2,4-difluoro-3-[5-(2-methoxy-ethoxy)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-3-fluoro-benzenesulfonamide and any pharmaceutically acceptable salts thereof.

46. The method of claim 1, wherein said compound having the structure of Formula IIIm is N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-4-isopropyl-benzenesulfonamide and any pharmaceutically acceptable salts thereof.

47. The method of claim 1, wherein said compound having the structure of Formula IIIm is N-[3-(5-chloro -1H -pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-4-ethyl-benzenesulfonamide and any pharmaceutically acceptable salts thereof.

48. The method of claim 1, wherein said compound having the structure of Formula IIIm is N-[2,4-difluoro-3-(1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-2,5-dimethoxy-benzenesulfonamide and any pharmaceutically acceptable salts thereof.

49. The method of claim 1, wherein said compound having the structure of Formula IIIm is dimethylamine-1-sulfonic acid [3-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide and any pharmaceutically acceptable salts thereof.

50. The method of claim 1, wherein said compound having the structure of Formula IIIm is butane-1-sulfonic acid [3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2-fluoro-phenyl]-amide and any pharmaceutically acceptable salts thereof.

51. The method of claim 1, wherein said compound having the structure of Formula IIIm is N-[2,4-difluoro-3-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-ethanesulfonamide and any pharmaceutically acceptable salts thereof.

52. The method of claim 1, wherein said compound having the structure of Formula IIIm is propane-1-sulfonic acid [2,4-difluoro-3-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide and any pharmaceutically acceptable salts thereof.

53. The method of claim 1, wherein said compound having the structure of Formula IIIm is propane-1-sulfonic acid [2,4-difluoro-3-(5-morpholin-4-yl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide and any pharmaceutically acceptable salts thereof.

54. The method of claim 1, wherein said compound having the structure of Formula IIIm is propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide and any pharmaceutically acceptable salts thereof.

55. The method of claim 1, wherein said compound having the structure of Formula IIIm is propane-1-sulfonic acid {2,4-difluoro-3-[5-(4-trifluoromethyl-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide and any pharmaceutically acceptable salts thereof.

56. The method of claim 1, wherein said compound having the structure of Formula IIIm is propane-1-sulfonic acid [3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-amide and any pharmaceutically acceptable salts thereof.

57. The method of claim 1, wherein said compound having the structure of Formula IIIm is propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2-fluoro-phenyl}-amide and any pharmaceutically acceptable salts thereof.

58. The method of claim 1, wherein said compound having the structure of Formula IIIm is propane-1-sulfonic acid [3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2-fluoro-phenyl]-amide and any pharmaceutically acceptable salts thereof.

59. The method of claim 1, wherein said compound having the structure of Formula IIIm is propane-1-sulfonic acid [4-chloro-2-fluoro-3-(5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide and any pharmaceutically acceptable salts thereof.

60. The method of claim 1, wherein said compound having the structure of Formula IIIm is propane-1-sulfonic acid [2-fluoro-3-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-phenyl]-amide and any pharmaceutically acceptable salts thereof.

61. The method of claim 1, wherein said compound having the structure of Formula IIIm is propane-1-sulfonic acid {2,4-difluoro-3-[5-(2-methoxy-ethoxy)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide and any pharmaceutically acceptable salts thereof.

62. The method according to any one of claims 36-61 wherein said protein kinase is a mutant of B-Raf.

63. The method according to claim 62 wherein said protein kinase is a V600E mutant of B-Raf.

64. The method according to claim 62 wherein said disease or condition is melanoma.

65. The method according to claim 62 wherein said disease or condition is thyroid cancer.

66. The method according to claim 62 wherein said disease or condition is colorectal cancer.