Pyrrolotriazine derivatives useful for treating cancer through inhibition of aurora kinase

• US 8,338,594 B2
• Filed: 12/01/2006
• Issued: 12/25/2012
• Est. Priority Date: 12/02/2005
• Status: Expired due to Fees

• Current Assignee: Bayer Healthcare LLC (Bayer AG)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Magnuson, Steven, Dixon, Julie, Phillips, Barton, Khire, Uday, Wang, Lei, Zhang, Zhonghua, Patel, Manoj, Kumarasinghe, Ellalahewage Sathyajith, Wickens, Philip, Olague, Alan
• Primary Examiner(s): Balasubramanian, Venkataraman
• Application Number:
  US12/085,850
• Publication Number:
  US 20110021518A1
• Time in Patent Office: 2,216 Days
• Field of Search: 544/183, 514/243
• US Class Current: 544/183
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

This invention relates to novel compounds and processes for their preparation, methods of treating diseases, particularly Cancer, comprising administering said compounds, and methods of making pharmaceutical compositions for the treatment or prevention of disorders, particularly Cancer.

Claims

1. A compound of formula (I)

2. The compound of claim 1, wherein X is —

O—

.

3. The compound of claim 1, wherein X is —

NH—

.

4. The compound of claim 1, wherein R^3-1 is trifluoroethyl.

5. The compound of claim 1, wherein X and R^3-1 are taken together to form a heterocyclyl ring optionally substituted with alkyl, carboxamide, alkoxyalkyl, or dialkylamino.

6. The compound of claim 1, wherein R² is hydrogen and R⁴ is halogen.

7. The compound of claim 6, wherein R⁴ is fluorine.

8. The compound of claim 1, wherein R⁶ is hydrogen.

9. The compound of claim 1 having formula (Ia):

11. A process for preparing a compound of claim 1, comprising

[A] reacting a compound of formula (II)

12. The process of claim 11, wherein the compound of formula (III), has the formula (IIIa)

13. A pharmaceutical composition comprising a compound as defined in claim 1 and at least one pharmaceutically acceptable excipient.

14. A method of treating cancer of the breast, comprising administering to a mammal in need thereof an effective amount of a compound as defined in claim 1.

10. A compound having the formula:

4-amino-5-[4-(1H-benzimidazol-2-ylamino)phenyl]-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5-cyano-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(7-hydroxy-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(6-chloro-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-N-(2,2,2-trifluoroethyl)-5-(4-{[6-(trifluoromethyl)-1H-benzimidazol-2-yl]amino}phenyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(6-fluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(6-methoxy-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(6-bromo-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(6-tert-butyl-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(6-benzoyl-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,6-dichloro-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(6-chloro-5-fluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,6-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(6,7-dimethyl-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-[4-(1H-thieno[3,4-d]imidazol-2-ylamino)phenyl]-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(2,2-difluoro-5H-[1,3]dioxolo[4,5-f]benzimidazol-6-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-[4-(3H-imidazo[4,5-b]pyridin-2-ylamino)phenyl]-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[6-(4-methoxyphenyl)-1H-benzimidazol-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5-pyrrolidin-1-yl-3H-imidazo[4,5-b]pyridin-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-[4-(9H-purin-8-ylamino)phenyl]-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(7-methyl-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(6-nitro-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5-methoxy-3H-imidazo[4,5-b]pyridin-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(6-iodo-3H-imidazo[4,5-b]pyridin-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5-chloro-3H-imidazo[4,5-b]pyridin-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(6-phenoxy-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5-methyl-3H-imidazo[4,5-b]pyridin-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[6-(4-fluorophenoxy)-1H-benzimidazol-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(6-methyl-3H-imidazo[4,5-b]pyridin-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-N-(2,2,2-trifluoroethyl)-5-(4-{[6-(trifluoromethoxy)-1H-benzimidazol-2-yl]amino}phenyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(7-fluoro-6-phenoxy-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5-ethoxy-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[7-fluoro-6-(4-methylphenoxy)-1H-benzimidazol-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[7-fluoro-6-(4-fluorophenoxy)-1H-benzimidazol-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(1-methyl-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(7-fluoro-6-pyrrolidin-1-yl-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5-phenoxy-3H-imidazo[4,5-b]pyridin-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[7-fluoro-6-(2-fluorophenoxy)-1H-benzimidazol-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[7-fluoro-6-(3-fluorophenoxy)-1H-benzimidazol-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[7-fluoro-6-(2-methylphenoxy)-1H-benzimidazol-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[7-fluoro-6-(3-methylphenoxy)-1H-benzimidazol-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[7-fluoro-6-(isopropylamino)-1H-benzimidazol-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide trifluoroacetate;

5-{4-[(6-acetyl-1-methyl-1H-benzimidazol-2-yl)amino]phenyl}-4-amino-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(6-methyl-9H-purin-8-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5-morpholin-4-yl-3H-imidazo[4,5-b]pyridin-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[5-(cyclobutylamino)-3H-imidazo[4,5-b]pyridin-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[5-(cyclohexylamino)-3H-imidazo[4,5-b]pyridin-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[5-(3,4-dimethylphenoxy)-3H-imidazo[4,5-b]pyridin-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-[4-({5-[(3-fluorophenyl)thio]-3H-imidazo[4,5-b]pyridin-2-yl}amino)phenyl]-N-(2,2,2-trifluoro ethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-[4-({5-[(cyclohexylmethyl)amino]-3H-imidazo[4,5-b]pyridin-2-yl}amino)phenyl]-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[5-(isobutylamino)-3H-imidazo[4,5-b]pyridin-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-[4-({5-[(2-methoxyethyl)amino]-3H-imidazo[4,5-b]pyridin-2-yl}amino)phenyl]-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[5-(tert-butylamino)-3H-imidazo[4,5-b]pyridin-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[5-(propylamino)-3H-imidazo[4,5-b]pyridin-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-[4-({5-[(2-methoxyethyl)(methyl)amino]-3H-imidazo[4,5-b]pyridin-2-yl}amino)phenyl]-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[5-(cyclopropylamino)-3H-imidazo[4,5-b]pyridin-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[5-(3,3-difluoropyrrolidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]-3-fluorophenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(2,2-difluoro-5H-[1,3]dioxolo[4,5-f]benzimidazol-6-yl)amino]-3-fluorophenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(6-chloro-1H-benzimidazol-2-yl)amino]-3-fluorophenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{3-fluoro-4-[(5-methyl-3H-imidazo[4,5-b]pyridin-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{3-fluoro-4-[(5-morpholin-4-yl-3H-imidazo[4,5-b]pyridin-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{3-fluoro-4-[(5-pyrrolidin-1-yl-3H-imidazo[4,5-b]pyridin-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-[3-fluoro-4-(3H-imidazo[4,5-b]pyridin-2-ylamino)phenyl]-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5-chloro-6-fluoro-1H-benzimidazol-2-yl)amino]-3-fluorophenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-[3-fluoro-4-(1H-thieno[3,4-d]imidazol-2-ylamino)phenyl]-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5-benzoyl-1H-benzimidazol-2-yl)amino]-3-fluorophenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-[3-fluoro-4-(1H-imidazo[4,5-c]pyridin-2-ylamino)phenyl]-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{3-fluoro-4-[(7-methyl-1H-benzimidazol-2-yl)amino]phenyl}-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid;

4-amino-N-(tert-butyl)-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-ethylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N,N-dimethylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-6-(morpholin-4-ylcarbonyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine;

4-amino-N-cyclobutyl-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-N-cyclohexyl-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-(3-methylbutyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-N-(cyclopropylmethyl)-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

1-[(4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazin-6-yl)carbonyl]piperidine-4-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-(3-pyrrolidin-1-ylpropyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-(3-morpholin-4-ylpropyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-[2-(dimethylamino)ethyl]pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-N-cyclopentyl-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-(2-ethoxyethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-(2-hydroxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-(tetrahydro-2H-pyran-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-ethyl-N-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-ethyl-N-isopropylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-6-{[2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}pyrrolo[2,1-f][1,2,4]triazin-4-amine;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-isopropyl-N-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-methyl-N-propylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-[2-(dimethylamino)ethyl]-N-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-6-{[(3R)-3-(dimethylamino)pyrrolidin-1-yl]carbonyl}pyrrolo[2,1-f][1,2,4]triazin-4-amine;

5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-6-(pyrrolidin-1-ylcarbonyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-ethyl-N-propylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-6-[(4-methylpiperazin-1-yl)carbonyl]pyrrolo[2,1-f][1,2,4]triazin-4-amine;

4-[(4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazin-6-yl)carbonyl]piperazin-2-one;

4-amino-5-{4-[(5,7-difluoro-1H-benzimidazol-2-yl)amino]phenyl}-N-methyl-N-(tetrahydro-2H-pyran-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(7-fluoro-6-phenoxy-1H-benzimidazol-2-yl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid;

4-amino-5-{4-[(7-fluoro-6-phenoxy-1H-benzimidazol-2-yl)amino]phenyl}-N-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(7-fluoro-6-phenoxy-1H-benzimidazol-2-yl)amino]phenyl}-N-propylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(7-fluoro-6-phenoxy-1H-benzimidazol-2-yl)amino]phenyl}-N-isopropylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-N-cyclopropyl-5-{4-[(7-fluoro-6-phenoxy-1H-benzimidazol-2-yl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-N-ethyl-5-{4-[(7-fluoro-6-phenoxy-1H-benzimidazol-2-yl)amino]phenyl}-N-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

5-{4-[(7-fluoro-6-phenoxy-1H-benzimidazol-2-yl)amino]phenyl}-6-(piperidin-1-ylcarbonyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine;

5-{4-[(7-fluoro-6-phenoxy-1H-benzimidazol-2-yl)amino]phenyl}-6-(morpholin-4-ylcarbonyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine;

4-amino-N-ethyl-5-{4-[(5-pyrrolidin-1-yl-3H-imidazo[4,5-b]pyridin-2-yl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(7-fluoro-6-phenoxy-1H-benzimidazol-2-yl)amino]phenyl}-N-(2-methoxyethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-{4-[(7-fluoro-6-phenoxy-1H-benzimidazol-2-yl)amino]phenyl}-N-isobutylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-N-cyclopentyl-5-{4-[(7-fluoro-6-phenoxy-1H-benzimidazol-2-yl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

5-{4-[(7-fluoro-6-phenoxy-1H-benzimidazol-2-yl)amino]phenyl}-6-(pyrrolidin-1-ylcarbonyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine;

4-amino-N-(cyclopropylmethyl)-5-{4-[(7-fluoro-6-phenoxy-1H-benzimidazol-2-yl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[5-(4-methylphenyl)-3H-imidazo[4,5-b]pyridin-2-yl]amino}phenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-[4-({5-[3-(methoxymethyl)phenyl]-3H-imidazo[4,5-b]pyridin-2-yl}amino)phenyl]-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-N-(tert-butyl)-5-{4-[(6-chloro-3H-imidazo[4,5-b]pyridin-2-yl)amino]-3-fluorophenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-N-(tert-butyl)-5-{4-[(2,2-difluoro-5H-[1,3]dioxolo[4,5-f]benzimidazol-6-yl)amino]-3-fluorophenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

4-amino-5-(4-{[5-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl]amino}phenyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid;

4-amino-N-(2,2,2-trifluoroethyl)-5-(4-{[5-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl]amino}phenyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;

ethyl 4-amino-5-[4-(1H-benzimidazol-2-ylamino)phenyl]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate;

ethyl 4-amino-5-{4-[(5-methoxy-1H-benzimidazol-2-yl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate;

or a pharmaceutically acceptable salt thereof.