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• W2040736465 abstract "Purines constitute a structural class of protein ligands involved in mediating an astonishing array of metabolic processes and signal pathways in all living organisms. Synthesis of purine derivatives targeting specific purine-binding proteins in vivo could lead to versatile lead compounds for use as biological probes or drug candidates.We synthesized several libraries of 2,6, 9-trisubstituted purines using both solution- and solid-phase chemistry, and screened the compounds for inhibition of cyclin-dependent kinase (CDK) activity and human leukemic cell growth. Lead compounds were optimized by iterative synthesis based on structure-activity relationships (SARs), as well as analysis of several CDK-inhibitor cocrystal structures, to afford several interesting compounds including one of the most potent CDK inhibitors known to date. Unexpectedly, some compounds with similar CDK inhibitory activity arrested cellular proliferation at distinctly different phases of the cell cycle and another inhibitor directly induced apoptosis, bypassing cell-cycle arrest. Some of these compounds selectively inhibited growth of cells derived from specific tumors.2,6,9-Trisubstituted purines have various and potent biological activities, despite high concentrations of competing endogenous purine ligands in living cells. Purine libraries constitute a versatile source of small molecules that affect distinct biochemical pathways mediating different cellular functions." @default.
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• W2040736465 date "1999-06-01" @default.
• W2040736465 modified "2023-10-18" @default.
• W2040736465 title "Synthesis and application of functionally diverse 2,6,9-trisubstituted purine libraries as CDK inhibitors" @default.
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• W2040736465 doi "https://doi.org/10.1016/s1074-5521(99)80048-9" @default.
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