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pubmed:abstractText |
The possibility of deriving a potent, cell-penetrating inhibitor of human erythrocyte PI 4-kinase, competitive with respect to ATP, has been investigated in a series of purine derivatives and analogues. The purine nucleus is not essential for binding to the ATP site but offers the advantage of synthetic accessibility to its derivatives. The optimum substitution pattern in purine was found to be an electron-releasing substituent in the 6-position (e.g. amino, as in adenine, 1) and a compact, lipophilic group in either the 8-position or, preferably, the 9-position, suggesting the importance of the N-1 lone pair and hydrophobic contributions of the 8- and 9-substituents to binding. The most potent inhibitor synthesized was 9-cyclohexyladenine (54), which has an apparent Ki value of 3.7 microM.
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