Design and optimization of potent and orally bioavailable tetrahydronaphthalene raf inhibitors

Journal of Medicinal Chemistry

Volumn 54, Issue 6, 2011, Pages 1836-1846

  Gould, Alexandra E ^a   Adams, Ruth ^a   Adhikari, Sharmila ^a   Aertgeerts, Kathleen ^b   Afroze, Roushan ^a   Blackburn, Christopher ^a   Calderwood, Emily F ^a   Chau, Ryan ^a   Chouitar, Jouhara ^a   Duffey, Matthew O ^a   England, Dylan B ^a   Farrer, Cheryl ^a   Forsyth, Nancy ^a   Garcia, Khristofer ^a   Gaulin, Jeffery ^a   Greenspan, Paul D ^a   Guo, Ribo ^a   Harrison, Sean J ^a   Huang, Shih Chung ^a   Iartchouk, Natalia ^a   Janowik, Dave ^a   Kim, Mi Sook ^a   Kulkarni, Bheemashankar ^a   Langston, Steven P ^a   Liu, Jane X ^a   Ma, Li Ting ^a   Menon, Saurabh ^a   Mizutani, Hirotake ^a   Paske, Erin ^a   Renou, Christelle C ^a   Rezaei, Mansoureh ^a   Rowland, R Scott ^a   Sintchak, Michael D ^a   Smith, Michael D ^a   Stroud, Stephen G ^a   Tregay, Ming ^a   Tian, Yuan ^a   Veiby, Ole P ^a   Vos, Tricia J ^a   Vyskocil, Stepan ^a   Williams, Juliet ^a   Xu, Tianlin ^a   Yang, Johnny J ^a   Yano, Jason ^b   Zeng, Hongbo ^a   Zhang, Dong Mei ^a   Zhang, Qin ^a   Galvin, Katherine M ^a   more..

^a MILLENNIUM PHARMACEUTICALS INC   (United States)

^b Takeda San Diego Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 (1 AMINO 1 METHYLETHYL) N [7 [(7 OXO 5,6,7,8 TETRAHYDRO 1,8 NAPHTHYRIDIN 4 YL)OXY] 1,2,3,4 TETRAHYDRONAPHTHALEN 2 YL] 5 (TRIFLUOROMETHYL)BENZAMIDE; 3 [(DIMETHYLAMINO)METHYL] N [7 [(7 OXO 5,6,7,8 TETRAHYDRO 1,8 NAPHTHYRIDIN 4 YL)OXO] 1,2,3,4 TETRAHYDRONAPHTHALEN 2 YL] 5 (TRIFLUOROMETHYL)BENZAMIDE; B RAF KINASE; ML 721; ML 786; N [3 [(ISOPROPYLAMINO)METHYL] 5 (TRIFLUOROMETHYL)PHENYL] 7 [(7 OXO 5,6,7,8 TETRAHYDRO 1,8 NAPHTHYRIDIN 4 YL)OXY] 1,2,3,4 TETRAHYDRONAPHTHALENE 2 CARBOXAMIDE; TETRALIN DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; CANCER INHIBITION; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DESIGN; DRUG STRUCTURE; ENZYME INHIBITION; IC 50; MELANOMA; MOUSE; NONHUMAN; PROCESS OPTIMIZATION; SINGLE DRUG DOSE;

ADMINISTRATION, ORAL; ANIMALS; ANTINEOPLASTIC AGENTS; BIOLOGICAL AVAILABILITY; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; MELANOMA, EXPERIMENTAL; MICE; MICE, NUDE; MODELS, MOLECULAR; MUTATION; PROTO-ONCOGENE PROTEINS B-RAF; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TETRAHYDRONAPHTHALENES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 79952811933     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm101479y     Document Type: Article

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