Structure-guided design of aminopyrimidine amides as potent, selective inhibitors of lymphocyte specific kinase: Synthesis, structure-activity relationships, and inhibition of in vivo T cell activation

Journal of Medicinal Chemistry

Volumn 51, Issue 6, 2008, Pages 1681-1694

  DiMauro, Erin F ^a   Newcomb, John ^a   Nunes, Joseph J ^a   Bemis, Jean E ^a   Boucher, Christina ^a   Chai, Lilly ^a   Chaffee, Stuart C ^a   Deak, Holly L ^a   Epstein, Linda F ^a   Faust, Ted ^a   Gallant, Paul ^a   Gore, Anu ^a   Gu, Yan ^a   Henkle, Brad ^a   Hsieh, Faye ^a   Huang, Xin ^a   Kim, Joseph L ^a   Lee, Josie H ^a   Martin, Matthew W ^a   McGowan, David C ^a   Metz, Daniela ^a   Mohn, Deanna ^a   Morgenstern, Kurt A ^a   Oliveira Dos Santos, Antonio ^a   Patel, Vinod F ^a   Powers, David ^a   Rose, Paul E ^a   Schneider, Stephen ^a   Tomlinson, Susan A ^a   Tudor, Yan Yan ^a   Turci, Susan M ^a   Welcher, Andrew ^a   Zhao, Huilin ^a   Zhu, Li ^a   Zhu, Xiaotian ^a   more..

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 METHYL N [2 [[4 (4 METHYL 1 PIPERAZINYL)PHENYL]AMINO] 5 PYRIMIDINYL] 5 [[[[3 (TRIFLUOROMETHYL)PHENYL]CARBONYL]AMINO]BENZAMIDE; AMIDE; AMINOPYRIMIDINE AMIDE DERIVATIVE; AMINOQUINAZOLINE DERIVATIVE; CD3 ANTIBODY; INTERLEUKIN 2; PROTEIN KINASE INHIBITOR; PROTEIN KINASE LCK; UNCLASSIFIED DRUG;

ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; DRUG ACTIVITY; DRUG INHIBITION; DRUG STRUCTURE; DRUG SYNTHESIS; IN VIVO STUDY; MOUSE; NONHUMAN; T LYMPHOCYTE ACTIVATION;

ADMINISTRATION, ORAL; AMIDES; ANIMALS; CELL PROLIFERATION; CRYSTALLOGRAPHY, X-RAY; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; ENZYME ACTIVATION; FEMALE; HUMANS; INTERLEUKIN-2; KILLER CELLS, NATURAL; LIPOPOLYSACCHARIDES; LYMPHOCYTE SPECIFIC PROTEIN TYROSINE KINASE P56(LCK); MALE; MICE; MICE, INBRED BALB C; MICE, KNOCKOUT; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN KINASE INHIBITORS; PYRIMIDINES; RATS; RATS, SPRAGUE-DAWLEY; SIGNAL TRANSDUCTION; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; T-LYMPHOCYTES;

EID: 41149146105     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm7010996     Document Type: Article

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64. m of ATP with respect to 1 μM peptide substrate.
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67. 50 = 3.0 μM).
68. 50)(mouse fu) = (175 nM)(0.022) = 4 nM.