CERTAIN CHEMICAL ENTITES, COMPOSITIONS, AND METHODS

• US 20150246885A1
• Filed: 09/24/2013
• Published: 09/03/2015
• Est. Priority Date: 09/24/2012
• Status: Active Grant

• Current Assignee: NeuPharma, Inc.
• Original Assignee: Yongliang Zhu
• Inventors: Qian, Xiangping, Zhu, Yong-liang
• Granted Patent: US 9,688,635 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61J 1/03 for pills or tablets containers for pills or tablets with special dispensing means therefor B65D83/04
• CPC Class Codes: A61J 1/05 for collecting, storing or administering blood, plasma or medical fluids multiple bags systems for separating or storing blood components A61M1/0209; Infusion or perfusion containers
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 215/14 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 239/74 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring

Abstract

Chemical entities that are kinase inhibitors, pharmaceutical compositions and methods of treatment of cancer are described.

Claims

1. A compound of Formula I

2. The compound or pharmaceutically acceptable salt of claim 1, wherein R₁, R₂, and R₃ are independently hydrogen, cyano, halo, optionally substituted alkoxy, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, or optionally substituted aminosulfonyl.

3. The compound or pharmaceutically acceptable salt of claim 2, wherein R₁, R₂, and R₃ are independently hydrogen, cyano, or halo.

4. The compound or pharmaceutically acceptable salt of claim 3, wherein R₁ and R₂ are independently hydrogen, fluoro or chloro.

5. The compound or pharmaceutically acceptable salt of claim 3, wherein R₃ is hydrogen.

6. The compound or pharmaceutically acceptable salt of any one of claims 1 to 4, wherein R₄ is chosen from hydrogen, optionally substituted lower alkyl, optionally substituted aryl, and optionally substituted heteroaryl.

7. The compound or pharmaceutically acceptable salt of claim 6, wherein R₄ is hydrogen or optionally substituted lower alkyl.

8. The compound or pharmaceutically acceptable salt of claim 7, wherein R₄ is hydrogen.

9. The compound or pharmaceutically acceptable salt of any one of claims 1 to 8, wherein R₅ is —

COR₇, —

CO₂R₇, —

CONR₇R₈, —

C(NR₉)NR₇R₈, —

C(NCN)NR₇R₈, —

SO₂R₇, or —

SO₂NR₇R₈, and wherein R₇ is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; and

R₈ and R₉ are independently hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl.

10. The compound or pharmaceutically acceptable salt of claim 9, wherein R₅ is —

COR₇, —

CONR₇R₈, or —

SO₂R₇.

11. The compound or pharmaceutically acceptable salt of claim 9 or 10, wherein, whenever present, R₇ is optionally substituted alkyl, optionally substituted aryl, or optionally substituted heteroaryl;

and R₈ and R₉ are independently hydrogen or optionally substituted alkyl.

12. The compound or pharmaceutically acceptable salt of claim 9 or 10, wherein R₇ and R₈ are joined together with any intervening atoms to form an optionally substituted 4- to 8-membered heterocycloalkyl ring.

13. The compound or pharmaceutically acceptable salt of any one of claims 1 to 5 wherein R₄ and R₅ are joined together with any intervening atoms to form an optionally substituted 4- to 8-membered heterocycloalkyl ring.

14. The compound or pharmaceutically acceptable salt of any one of claims 1 to 13 wherein Z₁ is 1,5-naphthyridin-2-yl, 1,7-naphthyridin-6-yl, 1H-pyrazolo[3,4-b]pyrazin-3-yl, 1H-pyrazolo[3,4-b]pyridin-3-yl, 5H-pyrrolo[2,3-b]pyrazin-7-yl, 7H-pyrrolo[2,3-c]pyridazin-5-yl, 7H-pyrrolo[2,3-d]pyrimidin-5-yl, benzo[d]oxazol-5-yl, benzo[d]oxazol-6-yl, benzo[d]thiazol-6-yl, oxazolo[5,4-b]pyridin-5-yl, pyrido[3,4-b]pyrazin-7-yl, quinazolin-6-yl, or quinolin-6-yl.

15. The compound or pharmaceutically acceptable salt of any one of claims 1 to 14 wherein, for each occurrence, R₆ is independently hydrogen, cyano, halo, hydroxy, carboxy, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkoxycarbonyl, optionally substituted alkyl, optionally substituted aryloxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted amino, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, or optionally substituted aminosulfonyl.

16. The compound or pharmaceutically acceptable salt of claim 15, wherein, for each occurrence, R₆ is independently hydrogen, cyano, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted amino, optionally substituted alkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl.

17. The compound or pharmaceutically acceptable salt of claim 16, wherein, for each occurrence, R₆ is independently optionally substituted aryl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl.

18. The compound or pharmaceutically acceptable salt of claim 17, wherein, for each occurrence, R₆ is independently optionally substituted morpholinyl, optionally substituted piperazinyl, optionally substituted pyrrolidinyl, optionally substituted piperidinyl, optionally substituted imidazolyl, optionally substituted pyrazolyl, or optionally substituted pyridyl.

19. The compound or pharmaceutically acceptable salt of any one of claims 1 to 18, wherein m is 0, 1, 2 or 3.

20. The compound or pharmaceutically acceptable salt of claim 19, wherein m is 0.

21. The compound or pharmaceutically acceptable salt of claim 20, wherein m is 1.

23. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound or pharmaceutically acceptable salt of any one of claims 1 to 22.

24. A pharmaceutical composition of claim 23, wherein the composition is formulated in a form chosen from the group consisting of tablets, capsules, powders, liquids, suspensions, suppositories, and aerosols.

25. A packaged pharmaceutical composition comprising a pharmaceutical composition of claim 23 or 24 and instructions for using the composition to treat a subject suffering from cancer.

26. A method of treating cancer in a subject which comprises administering to a subject in need thereof a therapeutically effective amount of a compound or pharmaceutically acceptable salt of any one of claims 1 to 22.

27. The method of claim 26, wherein the cancer is colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, thyroid cancer, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chondroma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing'"'"'s tumor, leiomyosarcoma, rhabdomyosarcoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, thyroid cancer, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms'"'"' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, non-small cell lung cancer, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma, retinoblastoma, leukemia, acute lymphocytic leukemia and acute myelocytic leukemia (myeloblastic, promyelocytic, myelomonocytic, monocytic and erythroleukemia);

chronic leukemia (chronic myelocytic (granulocytic) leukemia and chronic lymphocytic leukemia); and

polycythemia vera, lymphoma (Hodgkin'"'"'s disease and non-Hodgkin'"'"'s disease), multiple myeloma, Waldenstrom'"'"'s macroglobulinemia, or heavy chain disease.

28. The method of claim 27, wherein the cancer is melanoma, non-small cell lung cancer, colon cancer, thyroid cancer, or ovarian cancer.

29. A method of treating a disorder mediated by Raf in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound or pharmaceutically acceptable salt of any one of claims 1 to 22.

30. A method of treating a disorder in a subject in need thereof, comprising:

a. determining the presence or absence of a BRAF mutation in a biological sample isolated from the subject; and

b. if a BRAF mutation is determined to be present in the subject, administering to the subject a therapeutically effective amount of a compound or pharmaceutically acceptable salt of any one of claims 1 to 22.

31. The method of claim 30, wherein the BRAF mutation is in codon 600.

32. The method of claim 30, wherein the BRAF mutation is V600E.

33. The method of claim 30, wherein determining the presence or absence of the BRAF mutation comprises amplifying BRAF nucleic acid from the biological sample and sequencing the amplified nucleic acid.

34. The method of claim 30, wherein determining the presence or absence of the BRAF mutation comprises detecting a mutant BRAF polypeptide in the biological sample using a binding agent to a mutant BRAF polypeptide.

35. The method of claim 34, wherein the binding agent is an antibody.

36. The method of claim 30, wherein the biological sample is isolated from a tumor of the subject.

37. The method of any one of claims 29-36, wherein the disorder is cancer.

38. The method of claim 37, wherein the cancer is colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, thyroid cancer, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chondroma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing'"'"'s tumor, leiomyosarcoma, rhabdomyosarcoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms'"'"' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, non-small cell lung cancer, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma, retinoblastoma, leukemia, acute lymphocytic leukemia and acute myelocytic leukemia (myeloblastic, promyelocytic, myelomonocytic, monocytic and erythroleukemia);

chronic leukemia (chronic myelocytic (granulocytic) leukemia and chronic lymphocytic leukemia); and

polycythemia vera, lymphoma (Hodgkin'"'"'s disease and non-Hodgkin'"'"'s disease), multiple myeloma, Waldenstrom'"'"'s macroglobulinemia, or heavy chain disease.

39. The method of claim 38, wherein the cancer is melanoma, non-small cell lung cancer, colon cancer, thyroid cancer, or ovarian cancer.

40. The method of any one of claims 26-39, further comprising administering an additional anti-cancer and/or cytotoxic agent.

22. A compound or pharmaceutically acceptable salt chosen from the group consisting of:

N-(2-chloro-5-fluoro-3-(quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-5-fluoro-3-(3-methylquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-3-(3-cyanoquinoline-6-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(2-chloro-5-fluoro-3-(3-methoxyquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-3-(3-(4-chlorophenyl)quinoline-6-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(2-chloro-5-fluoro-3-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-5-fluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-5-fluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-5-fluoro-3-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-5-fluoro-3-(quinazoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-5-fluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-5-fluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-5-fluoro-3-(1,5-naphthyridine-2-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(benzo[d]oxazole-6-carbonyl)-2-chloro-5-fluorophenyl)propane-1-sulfonamide,

N-(3-(benzo[d]oxazole-5-carbonyl)-2-chloro-5-fluorophenyl)propane-1-sulfonamide,

N-(2-chloro-5-fluoro-3-(oxazolo[5,4-b]pyridine-5-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(benzo[d]thiazole-6-carbonyl)-2-chloro-5-fluorophenyl)propane-1-sulfonamide,

N-(2-chloro-3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(2-chloro-3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(2-chloro-3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(2-chloro-3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(2-chloro-3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(2-chloro-4,5-difluoro-3-(quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-4,5-difluoro-3-(3-methylquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-3-(3-cyanoquinoline-6-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(2-chloro-4,5-difluoro-3-(3-methoxyquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-3-(3-(4-chlorophenyl)quinoline-6-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(2-chloro-4,5-difluoro-3-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-4,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-4,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-4,5-difluoro-3-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-4,5-difluoro-3-(quinazoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-4,5-difluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-4,5-difluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)propane-1-sulfonamide,

N-(2-chloro-4,5-difluoro-3-(1,5-naphthyridine-2-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(benzo[d]oxazole-6-carbonyl)-2-chloro-4,5-difluorophenyl)propane-1-sulfonamide,

N-(3-(benzo[d]oxazole-5-carbonyl)-2-chloro-4,5-difluorophenyl)propane-1-sulfonamide,

N-(2-chloro-4,5-difluoro-3-(oxazolo[5,4-b]pyridine-5-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(benzo[d]thiazole-6-carbonyl)-2-chloro-4,5-difluorophenyl)propane-1-sulfonamide,

N-(2-chloro-3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(2-chloro-3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(2-chloro-3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(2-chloro-3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(2-chloro-3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-fluoro-5-(3-methylquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(3-cyanoquinoline-6-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(3-fluoro-5-(3-methoxyquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(3-(4-chlorophenyl)quinoline-6-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(3-fluoro-5-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-fluoro-5-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-fluoro-5-(quinazoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-fluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-fluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-fluoro-5-(1,5-naphthyridine-2-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(benzo[d]oxazole-6-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(3-(benzo[d]oxazole-5-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(3-fluoro-5-(oxazolo[5,4-b]pyridine-5-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(benzo[d]thiazole-6-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(3-fluoro-5-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-fluoro-5-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-5-fluorophenyl)propane-1-sulfonamide,

N-(2,5-difluoro-3-(quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,5-difluoro-3-(3-methylquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(3-cyanoquinoline-6-carbonyl)-2,5-difluorophenyl)propane-1-sulfonamide,

N-(2,5-difluoro-3-(3-methoxyquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(3-(4-chlorophenyl)quinoline-6-carbonyl)-2,5-difluorophenyl)propane-1-sulfonamide,

N-(2,5-difluoro-3-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,5-difluoro-3-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,5-difluoro-3-(quinazoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,5-difluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,5-difluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,5-difluoro-3-(1,5-naphthyridine-2-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(benzo[d]oxazole-6-carbonyl)-2,5-difluorophenyl)propane-1-sulfonamide,

N-(3-(benzo[d]oxazole-5-carbonyl)-2,5-difluorophenyl)propane-1-sulfonamide,

N-(2,5-difluoro-3-(oxazolo[5,4-b]pyridine-5-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(benzo[d]thiazole-6-carbonyl)-2,5-difluorophenyl)propane-1-sulfonamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-2,5-difluorophenyl)propane-1-sulfonamide,

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-2,5-difluorophenyl)propane-1-sulfonamide,

N-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-2,5-difluorophenyl)propane-1-sulfonamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-2,5-difluorophenyl)propane-1-sulfonamide,

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-2,5-difluorophenyl)propane-1-sulfonamide,

N-(2,5-difluoro-3-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,5-difluoro-3-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-2,5-difluorophenyl)propane-1-sulfonamide,

N-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-2,5-difluorophenyl)propane-1-sulfonamide,

N-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3,4-difluoro-5-(3-methylquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(3-cyanoquinoline-6-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(3,4-difluoro-5-(3-methoxyquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(3-(4-chlorophenyl)quinoline-6-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(3,4-difluoro-5-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3,4-difluoro-5-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3,4-difluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3,4-difluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)propane-1-sulfonamide,

N-(3,4-difluoro-5-(1,5-naphthyridine-2-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(benzo[d]oxazole-6-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(3-(benzo[d]oxazole-5-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(3,4-difluoro-5-(oxazolo[5,4-b]pyridine-5-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(benzo[d]thiazole-6-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(3,4-difluoro-5-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3,4-difluoro-5-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-4,5-difluorophenyl)propane-1-sulfonamide,

N-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,4,5-trifluoro-3-(3-methylquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(3-cyanoquinoline-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,

N-(2,4,5-trifluoro-3-(3-methoxyquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(3-(4-chlorophenyl)quinoline-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,

N-(2,4,5-trifluoro-3-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,4,5-trifluoro-3-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,4,5-trifluoro-3-(quinazoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,4,5-trifluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,4,5-trifluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,4,5-trifluoro-3-(1,5-naphthyridine-2-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(benzo[d]oxazole-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,

N-(3-(benzo[d]oxazole-5-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,

N-(2,4,5-trifluoro-3-(oxazolo[5,4-b]pyridine-5-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(benzo[d]thiazole-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,

N-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,

N-(2,4,5-trifluoro-3-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(2,4,5-trifluoro-3-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)propane-1-sulfonamide,

N-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,

N-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-2,4,5-trifluorophenyl)propane-1-sulfonamide,

1-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-fluoro-5-(3-methylquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-(3-cyanoquinoline-6-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-fluoro-5-(3-methoxyquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluorophenyl)-3-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(4-chlorophenyl)-3-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(3-chlorophenyl)-3-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(3-fluoro-5-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluorophenyl)-3-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea,

1-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(4-chlorophenyl)-3-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea,

1-(3-fluoro-5-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-fluoro-5-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-fluoro-5-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-fluoro-5-(quinazoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-fluoro-5-(quinazoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(3,4-difluorophenyl)-3-(3-fluoro-5-(quinazoline-6-carbonyl)phenyl)urea,

1-(3-fluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluorophenyl)-3-(3-fluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)urea,

1-(3-fluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluorophenyl)-3-(3-fluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)urea,

1-(3-fluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-fluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(3-fluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(3-fluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-fluoro-5-(1,5-naphthyridine-2-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-fluoro-5-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-(benzo[d]oxazole-6-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(benzo[d]oxazole-5-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(benzo[d]thiazole-6-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-5-fluorophenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(3-methylquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-(3-cyanoquinoline-6-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(3-methoxyquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea,

1-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(4-chlorophenyl)-3-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(3-chlorophenyl)-3-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(2,5-difluoro-3-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea,

1-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(4-chlorophenyl)-3-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea,

1-(2,5-difluoro-3-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(quinazoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(quinazoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(2,5-difluoro-3-(quinazoline-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea,

1-(2,5-difluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea,

1-(2,5-difluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea,

1-(2,5-difluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(2,5-difluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(2,5-difluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(1,5-naphthyridine-2-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(2,5-difluoro-3-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-(benzo[d]oxazole-6-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(benzo[d]oxazole-5-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(benzo[d]thiazole-6-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-2,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-chlorophenyl)-3-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)urea,

1-(4-chloro-3-fluorophenyl)-3-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)urea,

1-(3-chloro-4-fluorophenyl)-3-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)urea,

1-(4-chlorophenyl)-3-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)urea,

1-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea,

1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)urea,

1-(3,4-difluoro-5-(3-methylquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-(3-cyanoquinoline-6-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluoro-5-(3-methoxyquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea,

1-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(4-chlorophenyl)-3-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(3-chlorophenyl)-3-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(3,4-difluoro-5-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea,

1-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(4-chlorophenyl)-3-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea,

1-(3,4-difluoro-5-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluoro-5-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluoro-5-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(4-chlorophenyl)-3-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)urea,

1-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea,

1-(4-chloro-3-fluorophenyl)-3-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)urea,

1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)urea,

1-(3-chloro-4-fluorophenyl)-3-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)urea,

1-(3,4-difluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea,

1-(3,4-difluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3-(3,4-difluorophenyl)urea,

1-(3,4-difluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(3,4-difluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(4-fluorophenyl)urea,

1-(3,4-difluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluoro-5-(1,5-naphthyridine-2-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3,4-difluoro-5-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)-3-(3-fluorophenyl)urea,

1-(3-(benzo[d]oxazole-6-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(benzo[d]oxazole-5-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(benzo[d]thiazole-6-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-4,5-difluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-methylquinoline-6-carbonyl)phenyl)urea,

1-(3-(3-cyanoquinoline-6-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-methoxyquinoline-6-carbonyl)phenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(3,4-difluorophenyl)-3-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(4-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(4-chlorophenyl)-3-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(3-chlorophenyl)-3-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea,

1-(3,4-difluorophenyl)-3-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea,

1-(4-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea,

1-(4-chlorophenyl)-3-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)urea,

1-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(quinazoline-6-carbonyl)phenyl)urea,

1-(4-fluorophenyl)-3-(2,4,5-trifluoro-3-(quinazoline-6-carbonyl)phenyl)urea,

1-(3,4-difluorophenyl)-3-(2,4,5-trifluoro-3-(quinazoline-6-carbonyl)phenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)urea,

1-(3,4-difluorophenyl)-3-(2,4,5-trifluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)urea,

1-(3,4-difluorophenyl)-3-(2,4,5-trifluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)urea,

1-(4-fluorophenyl)-3-(2,4,5-trifluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)urea,

1-(4-fluorophenyl)-3-(2,4,5-trifluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(1,5-naphthyridine-2-carbonyl)phenyl)urea,

1-(3-fluorophenyl)-3-(2,4,5-trifluoro-3-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)urea,

1-(3-(benzo[d]oxazole-6-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(benzo[d]oxazole-5-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(benzo[d]thiazole-6-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea,

1-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-2,4,5-trifluorophenyl)-3-(3-fluorophenyl)urea,

1-(4-fluorophenyl)-3-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)urea,

1-(3,4-difluorophenyl)-3-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)urea,

1-(3,5-difluorophenyl)-3-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)urea,

4-fluoro-N-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)benzamide,

3,5-difluoro-N-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)benzamide,

3,4-difluoro-N-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)benzamide,

3,4-difluoro-N-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)benzamide,

4-fluoro-N-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)benzamide,

3-chloro-N-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)benzamide,

4-chloro-3-fluoro-N-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)benzamide,

4-chloro-N-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)-3-(trifluoromethyl)benzamide,

4-chloro-N-(3-fluoro-5-(quinoline-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(3-fluoro-5-(3-methylquinoline-6-carbonyl)phenyl)benzamide,

N-(3-(3-cyanoquinoline-6-carbonyl)-5-fluorophenyl)-3-fluorobenzamide,

3-fluoro-N-(3-fluoro-5-(3-methoxyquinoline-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide,

3,4-difluoro-N-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide,

4-fluoro-N-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide,

4-chloro-N-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide,

3-chloro-N-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide,

4-chloro-N-(3-fluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(trifluoromethyl)benzamide,

3-fluoro-N-(3-fluoro-5-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide,

3,4-difluoro-N-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide,

4-fluoro-N-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide,

4-chloro-N-(3-fluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(3-fluoro-5-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(3-fluoro-5-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(3-fluoro-5-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)benzamide,

N-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-5-fluorophenyl)-3-fluorobenzamide,

N-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-5-fluorophenyl)-3-fluorobenzamide,

3-fluoro-N-(3-fluoro-5-(quinazoline-6-carbonyl)phenyl)benzamide,

4-fluoro-N-(3-fluoro-5-(quinazoline-6-carbonyl)phenyl)benzamide,

3,4-difluoro-N-(3-fluoro-5-(quinazoline-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(3-fluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)benzamide,

3,4-difluoro-N-(3-fluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(3-fluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)benzamide,

3,4-difluoro-N-(3-fluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(3-fluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide,

4-fluoro-N-(3-fluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide,

4-fluoro-N-(3-fluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide,

3-fluoro-N-(3-fluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide,

3-fluoro-N-(3-fluoro-5-(1,5-naphthyridine-2-carbonyl)phenyl)benzamide,

3-fluoro-N-(3-fluoro-5-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)benzamide,

N-(3-(benzo[d]oxazole-6-carbonyl)-5-fluorophenyl)-3-fluorobenzamide,

N-(3-(benzo[d]oxazole-5-carbonyl)-5-fluorophenyl)-3-fluorobenzamide,

N-(3-(benzo[d]thiazole-6-carbonyl)-5-fluorophenyl)-3-fluorobenzamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-5-fluorophenyl)-3-fluorobenzamide,

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-5-fluorophenyl)-3-fluorobenzamide,

N-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-5-fluorophenyl)-3-fluorobenzamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-5-fluorophenyl)-3-fluorobenzamide,

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-5-fluorophenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(quinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(3-methylquinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(3-(3-cyanoquinoline-6-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(3-methoxyquinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-3,4-difluorobenzamide,

N-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-4-fluorobenzamide,

4-chloro-N-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide,

3-chloro-N-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide,

4-chloro-N-(2,5-difluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(trifluoromethyl)benzamide,

N-(2,5-difluoro-3-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3,4-difluorobenzamide,

N-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-4-fluorobenzamide,

4-chloro-N-(2,5-difluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide,

N-(2,5-difluoro-3-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(quinazoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(quinazoline-6-carbonyl)phenyl)-4-fluorobenzamide,

N-(2,5-difluoro-3-(quinazoline-6-carbonyl)phenyl)-3,4-difluorobenzamide,

N-(2,5-difluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)-3,4-difluorobenzamide,

N-(2,5-difluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3,4-difluorobenzamide,

N-(2,5-difluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-4-fluorobenzamide,

N-(2,5-difluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-4-fluorobenzamide,

N-(2,5-difluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(1,5-naphthyridine-2-carbonyl)phenyl)-3-fluorobenzamide,

N-(2,5-difluoro-3-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)-3-fluorobenzamide,

N-(3-(benzo[d]oxazole-6-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(benzo[d]oxazole-5-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(benzo[d]thiazole-6-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-2,5-difluorophenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-3,4-difluorobenzamide,

N-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-4-fluorobenzamide,

3-chloro-N-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)benzamide,

4-chloro-N-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

4-chloro-N-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)-3-(trifluoromethyl)benzamide,

4-chloro-N-(3,4-difluoro-5-(quinoline-6-carbonyl)phenyl)benzamide,

N-(3,4-difluoro-5-(3-methylquinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(3-(3-cyanoquinoline-6-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(3-methoxyquinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3,4-difluorobenzamide,

N-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-4-fluorobenzamide,

4-chloro-N-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide,

3-chloro-N-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide,

4-chloro-N-(3,4-difluoro-5-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(trifluoromethyl)benzamide,

N-(3,4-difluoro-5-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-3,4-difluorobenzamide,

N-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)-4-fluorobenzamide,

4-chloro-N-(3,4-difluoro-5-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide,

N-(3,4-difluoro-5-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)-4-fluorobenzamide,

N-(3,4-difluoro-5-(quinazoline-6-carbonyl)phenyl)-3,4-difluorobenzamide,

N-(3,4-difluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(1,7-naphthyridine-6-carbonyl)phenyl)-3,4-difluorobenzamide,

N-(3,4-difluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)-3,4-difluorobenzamide,

N-(3,4-difluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-4-fluorobenzamide,

N-(3,4-difluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-4-fluorobenzamide,

N-(3,4-difluoro-5-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(1,5-naphthyridine-2-carbonyl)phenyl)-3-fluorobenzamide,

N-(3,4-difluoro-5-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)-3-fluorobenzamide,

N-(3-(benzo[d]oxazole-6-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(benzo[d]oxazole-5-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(benzo[d]thiazole-6-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide,

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-4,5-difluorophenyl)-3-fluorobenzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(quinoline-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(3-methylquinoline-6-carbonyl)phenyl)benzamide,

N-(3-(3-cyanoquinoline-6-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(3-methoxyquinoline-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide,

3,4-difluoro-N-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide,

4-fluoro-N-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide,

4-chloro-N-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide,

3-chloro-N-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)benzamide,

4-chloro-N-(2,4,5-trifluoro-3-(3-morpholinoquinoline-6-carbonyl)phenyl)-3-(trifluoromethyl)benzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(3-(pyrrolidin-1-yl)quinoline-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide,

3,4-difluoro-N-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide,

4-fluoro-N-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide,

4-chloro-N-(2,4,5-trifluoro-3-(3-(piperazin-1-yl)quinoline-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(3-(pyridin-3-yl)quinoline-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(3-((2-hydroxyethyl)amino)quinoline-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(3-(2-hydroxyethoxy)quinoline-6-carbonyl)phenyl)benzamide,

N-(3-(3-(1H-pyrazol-4-yl)quinoline-6-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide,

N-(3-(3-(1H-imidazol-1-yl)quinoline-6-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(quinazoline-6-carbonyl)phenyl)benzamide,

4-fluoro-N-(2,4,5-trifluoro-3-(quinazoline-6-carbonyl)phenyl)benzamide,

3,4-difluoro-N-(2,4,5-trifluoro-3-(quinazoline-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)benzamide,

3,4-difluoro-N-(2,4,5-trifluoro-3-(1,7-naphthyridine-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)benzamide,

3,4-difluoro-N-(2,4,5-trifluoro-3-(3-morpholino-1,7-naphthyridine-6-carbonyl)phenyl)benzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide,

4-fluoro-N-(2,4,5-trifluoro-3-(pyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide,

4-fluoro-N-(2,4,5-trifluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(2-morpholinopyrido[3,4-b]pyrazine-7-carbonyl)phenyl)benzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(1,5-naphthyridine-2-carbonyl)phenyl)benzamide,

3-fluoro-N-(2,4,5-trifluoro-3-(7-morpholino-1,5-naphthyridine-2-carbonyl)phenyl)benzamide,

N-(3-(benzo[d]oxazole-6-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide,

N-(3-(benzo[d]oxazole-5-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide,

N-(3-(benzo[d]thiazole-6-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyridine-3-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide,

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide,

N-(3-(5,7a-dihydro-4aH-pyrrolo[2,3-b]pyrazine-7-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide,

N-(3-(3a,7a-dihydro-1H-pyrazolo[3,4-b]pyrazine-3-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide, and

N-(3-(7,7a-dihydro-4aH-pyrrolo[2,3-c]pyridazine-5-carbonyl)-2,4,5-trifluorophenyl)-3-fluorobenzamide,

and pharmaceutically acceptable salts thereof.