Strategies to mitigate the bioactivation of 2-anilino-7-aryl-pyrrolo[2,1-f ][1,2,4]triazines: Identification of orally bioavailable, efficacious ALK inhibitors

Journal of Medicinal Chemistry

Volumn 55, Issue 1, 2012, Pages 115-125

  Mesaros, Eugen F ^a   Thieu, Tho V ^a   Wells, Gregory J ^a   Zificsak, Craig A ^a   Wagner, Jason C ^a   Breslin, Henry J ^a   Tripathy, Rabindranath ^a   Diebold, James L ^a   McHugh, Robert J ^a   Wohler, Ashley T ^a   Quail, Matthew R ^a   Wan, Weihua ^a   Lu, Lihui ^a   Huang, Zeqi ^a   Albom, Mark S ^a   Angeles, Thelma S ^a   Wells Knecht, Kevin J ^a   Aimone, Lisa D ^a   Cheng, Mangeng ^a   Ator, Mark A ^a   Ott, Gregory R ^a   Dorsey, Bruce D ^a   more..

^a CEPHALON INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 FLUORO 3 [4 [3 METHOXY 4 [7 (2 METHOXY PHENYL)PYRROLO[2,1 F][1,2,4]TRIAZIN 2 YLAMINO]PHENYL]PIPERIDIN 1 YL]PROPAN 2 OL; 2 [4 [3 METHOXY 4 [7 (2 METHOXY PHENYL)PYRROLO[2,1 F][1,2,4]TRIAZIN 2 YLAMINO]PHENYL]PIPERIDIN 1 YL] N METHYLACETAMIDE; 2 [4 [3 METHOXY 4 [7 (2 METHOXY PHENYL)PYRROLO[2,1 F][1,2,4]TRIAZIN 2 YLAMINO]PHENYL]PIPERIDIN 1 YL]ACETAMIDE; 2 [4 [3 METHOXY 4 [7 (3 METHOXY PYRIDIN 2 YL)PYRROLO[2,1 F][1,2,4]TRIAZIN 2 YLAMINO]PHENYL]PIPERIDIN 1 YL]ACETAMIDE TRIFLUOROACETIC ACID SALT; 2 [4 [3 METHOXY 4 [7 (3 METHOXY PYRIDIN 4 YL)PYRROLO[2,1 F][1,2,4]TRIAZIN 2 YLAMINO]PHENYL]PIPERIDIN 1 YL]ACETAMIDE; 2 [4 [4 [5 CHLORO 7 [2 (METHANESULFONYL METHYL AMINO)PHENYL]PYRROLO[2,1 F][1,2,4]TRIAZIN 2 YLAMINO] 3 METHOXYPHENYL]PIPERIDIN 1 YL]ACETAMIDE; 2 [4 [4 [5 HYDROXY 7 [2 (METHANESULFONYL METHYL AMINO)PHENYL]PYRROLO[2,1 F][1,2,4]TRIAZIN 2 YLAMINO] 3 METHOXYPHENYL]PIPERIDIN 1 YL]ACETAMIDE; 2 [4 [4 [7 (2 CYANO PHENYL)PYRROLO[2,1 F][1,2,4]TRIAZIN 2 YLAMINO] 3 METHOXY PHENYL]PIPERIDIN 1 YL]ACETAMIDE TRIFLUOROACETIC ACID SALT; 2 [4 [4 [7 (2,4 DIMETHOXY PHENYL)PYRROLO[2,1 F][1,2,4][1,2,4]TRIAZIN 2 YLAMINO] 3 METHOXY PHENYL]PIPERIDIN 1 YL]ACETAMIDE; 2 [4 [4 [7 [2 (METHANESULFONYL METHYL AMINO)PHENYL] 5 METHYLPYRROLO[2,1 F][1,2,4]TRIAZIN 2 YLAMINO] 3 METHOXY PHENYL]PIPERIDIN 1 YL]ACETAMIDE; 2 [4 [4 [7 [2 (METHANESULFONYL METHYL AMINO)PHENYL]PYRROLO[2,1 F][1,2,4]TRIAZIN 2 YLAMINO] 3 METHOXY PHENYL]PIPERIDIN 1 YL]ACETAMIDE; 2 AMINO 1 [4 [3 METHOXY 4 [7 (2 METHOXY PHENYL)PYRROLO[2,1 F][1,2,4]TRIAZIN 2 YLAMINO]PHENYL]PIPERIDIN 1 YL] 2 METHYL PROPAN 1 ONE; 2 ANILINO 7 ARYL PYRROLO[2,1 F][1,2,4]TRIAZINE DERIVATIVE; 3 [4 [3 METHOXY 4 [7 (2 METHOXY PHENYL)PYRROLO[2,1 F][1,2,4]TRIAZIN 2 YLAMINO]PHENYL]PIPERIDIN 1 YL]PROPANE 1,2 DIOL; [2 METHOXY 4 (1 METHYL PIPERIDIN 4 YL) PHENYL][7 (2 METHOXYPHENYL)PYRROLO[2,1 F][1,2,4]TRIAZIN 2 YL]AMINE; ANAPLASTIC LYMPHOMA KINASE; ANILINE; ANTINEOPLASTIC AGENT; AZETIDIN 2 YL [4 [3 METHOXY 4 [7 (2 METHOXY PHENYL)PYRROLO[2,1 F][1,2,4]TRIAZIN 2 YLAMINO]PHENYL]PIPERIDIN 1 YL]METHANONE; CYTOCHROME P450; DRUG METABOLITE; N [2 [2 (2 METHOXY 4 PIPERIDIN 4 YL PHENYLAMINO)PYRROLO [2,1 F][1,2,4]TRIAZIN 7 YL]PHENYL] N METHYL METHANESULFONAMIDE; N [2 [2 [4 [1 ( 2 HYDROXY PROPYL) PIPERIDIN 4 YL] 2 METHOXY PHENYLAMINO]PYRROLO[2,1 F][1,2,4]TRIAZIN 7 YL]PHENYL] N METHYL METHANESULFONAMIDE; N [2 [2 [4 [1 (2 HYDROXY ETHYL)PIPERIDIN 4 YL] 2 METHOXYHENYLAMINO PYRROLO[2,1 F][1,2,4]TRIAZIN 7 YL]PHENYL] N METHYL METHANESULFONAMIDE; N [2 [2 [5 FLUORO 4 [4 ( 2 HYDROXY PROPYL)PIPERAZIN 1 YL] 2 METHOXY PHENYLAMINO]PYRROLO[2,1 F][1,2,4]TRIAZIN 7 YL]PHENYL] N METHYLMETHANESULFONAMIDE; NITROGEN; PIPERIDINE DERIVATIVE; TRIAZINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; DRUG ACTIVITY; DRUG EFFICACY; DRUG IDENTIFICATION; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; MOUSE; NONHUMAN; OXIDATION; TUMOR XENOGRAFT;

ADMINISTRATION, ORAL; ANILINE COMPOUNDS; ANIMALS; ANTINEOPLASTIC AGENTS; BIOLOGICAL AVAILABILITY; MICE; MICE, SCID; MICROSOMES, LIVER; PYRROLES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTOR PROTEIN-TYROSINE KINASES; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZINES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84855833516     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm2010767     Document Type: Article

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