Optimization of 2-phenylaminoimidazo[4,5-h]isoquinolin-9-ones: Orally active inhibitors of lck kinase

Journal of Medicinal Chemistry

Volumn 46, Issue 8, 2003, Pages 1337-1349

  Goldberg, Daniel R ^a   Butz, Tanja ^a   Cardozo, Mario G ^a   Eckner, Robert J ^a   Hammach, Abdelhakim ^a   Huang, Jessica ^a   Jakes, Scott ^a   Kapadia, Suresh ^a   Kashem, Mohammed ^a   Lukas, Susan ^a   Morwick, Tina M ^a   Panzenbeck, Maret ^a   Patel, Usha ^a   Pav, Susan ^a   Peet, Gregory W ^a   Peterson, Jeffrey D ^a   Prokopowicz III, Anthony S ^a   Snow, Roger J ^a   Sellati, Rosemarie ^a   Takahashi, Hidenori ^a   Tan, Jonathan ^a   Tschantz, Matt A ^a   Wang, Xiao Jun ^a   Wang, Yong ^a   Wolak, John ^a   Xiong, Pla ^a   Moss, Neil ^a   more..

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 PHENYLAMINOIMIDAZO[4,5 H]ISOQUINOLIN 9 ONE DERIVATIVE; CD3 ANTIGEN; INTERLEUKIN 12; PROTEIN KINASE LCK; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; CYTOKINE PRODUCTION; DRUG ACTIVITY; DRUG DESIGN; DRUG EFFICACY; DRUG STRUCTURE; ENZYME INHIBITION; FEMALE; IN VIVO STUDY; MOLECULAR MODEL; MOUSE; NONHUMAN; T LYMPHOCYTE ACTIVATION;

ADMINISTRATION, ORAL; ANIMALS; ANTIBODIES, MONOCLONAL; ANTIGENS, CD3; BENZIMIDAZOLES; CRYSTALLOGRAPHY, X-RAY; ENZYME INHIBITORS; FEMALE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INTERLEUKIN-2; ISOQUINOLINES; JURKAT CELLS; LYMPHOCYTE SPECIFIC PROTEIN TYROSINE KINASE P56(LCK); MICE; MICE, INBRED BALB C; MODELS, MOLECULAR; MOLECULAR CONFORMATION; PROTEIN BINDING; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0037431414     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm020446l     Document Type: Article

References (22)

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22. During the course of our work, two crystal structures of the catalytic domain of lck in its active state were published. The results did not change any of the conclusions drawn from our initial model with hck. (a) Yamaguchi, H.; Hendrickson, W. A. Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation. Nature 1996, 384, 484-489. (b) Zhu, X.; Kim, J. L.; Newcomb, J. R.; Rose, P. E.; Stover, D. R.; Toledo, L. M.; Zhao, H.; Morgenstern, K. A. Structural analysis of the lymphocyte-specific kinase Lck in complex with non-selective and Src family selective kinase inhibitors. Structure 1999, 7, 651-661.