SAR maps: a new SAR visualization technique for medicinal chemists.
We present structure-activity relationship (SAR) maps, a new, intuitive method for visualizing SARs targeted specifically at medicinal chemists. The method renders an R-group decomposition of a chemical series as a rectangular matrix of cells, each representing a unique combination of R-groups and thus a unique compound. Color-coding the cells by chemical property or biological activity allows patterns to be easily identified and exploited. SAR maps allow the medicinal chemist to interactively analyze complicated datasets with multiple R-group dimensions, rapidly correlate substituent structure and biological activity, assess additivity of substituent effects, identify missing analogs and screening data, and create compelling graphical representations for presentation and publication. We believe that this method fills a long-standing gap in the medicinal chemist's toolset for understanding and rationalizing SAR.
Agrafiotis
Dimitris K
DK
Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 665 Stockton Drive, Exton, PA 19341, USA. dagrafio@prdus.jnj.com
Shemanarev
Maxim
M
Connolly
Peter J
PJ
Farnum
Michael
M
Lobanov
Victor S
VS
D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D008958:Models, Molecular; D008968:Molecular Conformation; D010879:Piperazines / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
D010879:Piperazines; D010880:Piperidines; D014230:Triazoles; D040301:Vascular Endothelial Growth Factor Receptor-2; D016203:CDC2 Protein Kinase