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| [[Image:2ofu.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_2ofu| PDB=2ofu | SCENE= }} | | {{STRUCTURE_2ofu| PDB=2ofu | SCENE= }} |
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| '''x-ray crystal structure of 2-aminopyrimidine carbamate 43 bound to Lck'''
| | ===x-ray crystal structure of 2-aminopyrimidine carbamate 43 bound to Lck=== |
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| ==Overview==
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| The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and NK cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. A small molecule inhibitor of Lck is expected to be useful in the treatment of T cell-mediated autoimmune and inflammatory disorders and/or organ transplant rejection. In this paper, we describe the synthesis, structure-activity relationships, and pharmacological characterization of 2-aminopyrimidine carbamates, a new class of compounds with potent and selective inhibition of Lck. The most promising compound of this series, 2,6-dimethylphenyl 2-((3,5-bis(methyloxy)-4-((3-(4-methyl-1-piperazinyl)propyl)oxy)phenyl)ami no)-4-pyrimidinyl(2,4-bis(methyloxy)phenyl)carbamate (43) exhibits good activity when evaluated in in vitro assays and in an in vivo model of T cell activation. | | The line below this paragraph, {{ABSTRACT_PUBMED_16884310}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16884310 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16884310}} |
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| ==Disease== | | ==Disease== |
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| [[Category: Kinase domain]] | | [[Category: Kinase domain]] |
| [[Category: Lck]] | | [[Category: Lck]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:49:11 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:41:18 2008'' |