Structure-aided optimization of kinase inhibitors derived from alsterpaullone. Export

@article{citeulike:3416053, abstract = {In order to perform computer-aided design of novel alsterpaullone derivatives, the vicinity of the entrance to the ATP-binding site was scanned for areas that could be useful as anchoring points for additional protein-ligand interactions. Based on the alignment of alsterpaullone in a CDK1/cyclin B homology model, substituents were attached to the 2-position of the parent scaffold to enable contacts within the identified areas. Synthesis of the designed structures revealed three derivatives (3-5) with kinase-inhibitory activity similar to alsterpaullone. The novel 2-cyanoethylalsterpaullone (7) proved to be the most potent paullone described so far, exhibiting inhibitory concentrations for CDK1/ cyclin B and GSK-3beta in the picomolar range.}, author = {Kunick, C. and Zeng, Z. and Gussio, R. and Zaharevitz, D. and Leost, M. and Totzke, F. and Sch\"{a}chtele, C. and Kubbutat, M. H. and Meijer, L. and Lemcke, T.}, citeulike-article-id = {3416053}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/cbic.200400099}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15696597}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15696597}, citeulike-linkout-3 = {http://scholar.google.com/scholar?hl=en&lr=&cluster=12338832733391321639&um=1&ie=UTF-8&sa=X&oi=science_links&resnum=1&ct=sl-allversions}, citeulike-linkout-4 = {http://www.sb-roscoff.fr/UPSMCT/Pub/33-Alsterpaullone.pdf}, citeulike-linkout-5 = {http://sbr.sb-roscoff.fr/CyCell/Articles/166-Alsterpaullone.pdf}, citeulike-linkout-6 = {http://hal.archives-ouvertes.fr/ccsd-00018743/en/}, doi = {10.1002/cbic.200400099}, issn = {1439-4227}, journal = {Chembiochem : a European journal of chemical biology}, keywords = {alsterpaullone, wnt}, month = {March}, number = {3}, pages = {541--549}, posted-at = {2008-10-15 23:26:16}, priority = {2}, title = {Structure-aided optimization of kinase inhibitors derived from alsterpaullone.}, url = {http://dx.doi.org/10.1002/cbic.200400099}, volume = {6}, year = {2005} }

TY - JOUR ID - citeulike:3416053 L3 - citeulike-article-id:3416053 N2 - In order to perform computer-aided design of novel alsterpaullone derivatives, the vicinity of the entrance to the ATP-binding site was scanned for areas that could be useful as anchoring points for additional protein-ligand interactions. Based on the alignment of alsterpaullone in a CDK1/cyclin B homology model, substituents were attached to the 2-position of the parent scaffold to enable contacts within the identified areas. Synthesis of the designed structures revealed three derivatives (3-5) with kinase-inhibitory activity similar to alsterpaullone. The novel 2-cyanoethylalsterpaullone (7) proved to be the most potent paullone described so far, exhibiting inhibitory concentrations for CDK1/ cyclin B and GSK-3beta in the picomolar range. IS - 3 JF - Chembiochem : a European journal of chemical biology SN - 1439-4227 EP - 549 TI - Structure-aided optimization of kinase inhibitors derived from alsterpaullone. VL - 6 SP - 541 KW - alsterpaullone KW - wnt AU - Kunick, C AU - Zeng, Z AU - Gussio, R AU - Zaharevitz, D AU - Leost, M AU - Totzke, F AU - Schächtele, C AU - Kubbutat, MH AU - Meijer, L AU - Lemcke, T PY - 2005/03// UR - http://dx.doi.org/10.1002/cbic.200400099 ER -