Reymond, J. L. The chemical space project. Acc. Chem. Res. 48, 722–730 (2015).
Murray, P. M., Tyler, S. N. G. Moseley, J. D. Beyond the numbers: charting chemical reaction space. Org. Process Res. Dev . 17, 40–46 (2013).
Buitrago Santanilla, A. et al. Nanomole-scale high-throughput chemistry for the synthesis of complex molecules. Science 347, 49–53 (2015).
Shevlin, M. Practical high-throughput experimentation for chemists. ACS Med. Chem. Lett. 8, 601–607 (2017).
Collins, K. D., Gensch, T. Glorius, F. Contemporary screening approaches to reaction discovery and development. Nat. Chem. 6, 859–871 (2014).
Troshin, K. Hartwig, J. F. Snap deconvolution: an informatics approach to high-throughput discovery of catalytic reactions. Science 357, 175–181 (2017).
Kutchukian, P. S. et al. Chemistry informer libraries: a chemoinformatics enabled approach to evaluate and advance synthetic methods. Chem. Sci. 7, 2604–2613 (2016).
Werner, M. et al. Seamless integration of dose-response screening and flow chemistry: efficient generation of structure–activity relationship data of β-secretase (BACE1) inhibitors. Angew. Chem. Int. Ed. 53, 1704–1708 (2014).
Desai, B. et al. Rapid discovery of a novel series of Abl kinase inhibitors by application of an integrated microfluidic synthesis and screening platform. J. Med. Chem. 56, 3033–3047 (2013).
Guetzoyan, L., Nikbin, N., Baxendale, I. R. Ley, S. V. Flow chemistry synthesis of zolpidem, alpidem and other GABAA agonists and their biological evaluation through the use of in-line frontal affinity chromatography. Chem. Sci. 4, 764–769 (2013).
Karageorgis, G., Dow, M., Aimon, A., Warriner, S. Nelson, A. Activity-directed synthesis with intermolecular reactions: development of a fragment into a range of androgen receptor agonists. Angew. Chem. Int. Ed. 54, 13538–13544 (2015).
Murray, J. B., Roughley, S. D., Matassova, N. Brough, P. A. Off-rate screening (ORS) by surface plasmon resonance. An efficient method to kinetically sample hit to lead chemical space from unpurified reaction products. J. Med. Chem. 57, 2845–2850 (2014).
Baranczak, A. et al. Integrated platform for expedited synthesis–purification–testing of small molecule libraries. ACS Med. Chem. Lett. 8, 461–465 (2017).
Price, A. K., MacConnell, A. B. Paegel, B. M. hνSABR: photochemical dose–response bead screening in droplets. Anal. Chem. 88, 2904–2911 (2016).
Vastl, J., Wang, T., Trinh, T. B. Spiegel, D. A. Encoded silicon-chip-based platform for combinatorial synthesis and screening. ACS Comb. Sci. 19, 255–261 (2017).
Goodnow, R. A. Jr, Dumelin, C. E. Keefe, A. D. DNA-encoded chemistry: enabling the deeper sampling of chemical space. Nat. Rev. Drug Discov. 16, 131–147 (2017).
Annis, D. A. et al. An affinity selection–mass spectrometry method for the identification of small molecule ligands from self-encoded combinatorial libraries. Discovery of a novel antagonist of E. coli dihydrofolate reductase. Int. J. Mass Spectrom. 238, 77–83 (2004).
Andrews, C. L., Ziebell, M. R., Nickbarg, E. Yang, X. in Protein and Peptide Mass Spectro
metry in Drug Discovery (eds Gross, M. L. et al.) 253−286 (John Wiley Sons, Hoboken, 2012).
O’Connell, T. N., Ramsay, J., Rieth, S. F., Shapiro, M. J. Stroh, J. G. Solution-based indirect affinity selection mass spectrometry – a general tool for high-throughput screening of pharmaceutical compound libraries. Anal. Chem. 86, 7413–7420 (2014).
Annis, D. A. et al. A general technique to rank protein-ligand binding affinities and determine allosteric versus direct binding site competition in compound mixtures. J. Am. Chem. Soc. 126, 15495–15503 (2004).
Cuozzo, J. W. et al. Discovery of a potent BTK inhibitor with a novel binding mode by using parallel selections with a DNA-encoded chemical library. ChemBioChem 18, 864–871 (2017).
Schneider, M. et al. Big data from pharmaceutical patents: a computational analysis of medicinal chemists’ bread and butter. J. Med. Chem. 59, 4385–4402 (2016).
Brown, D. G. Boström, J. Analysis of past and present synthetic methodologies on medicinal chemistry: where have all the new reactions gone? J. Med. Chem. 59, 4443–4458 (2016).
Aronov, A. M. et al. Flipped out: structure-guided design of selective pyrazolylpyrrole ERK inhibitors. J. Med. Chem. 50, 1280–1287 (2007).
Bruno, N. C., Tudge, M. T. Buchwald, S. L. Design and preparation of new palladium precatalysts for C–C and C–N cross-coupling reactions. Chem. Sci. 4, 916–920 (2013).
Anderson, D. R. et al. Pyrrolopyridine inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2). J. Med. Chem. 50, 2647–2654 (2007).
Huang, X. et al. Structure-based design and optimization of 2-aminothiazole-4-carboxamide as a new class of CHK1 inhibitors. Bioorg. Med. Chem. Lett. 23, 2590–2594 (2013).
Buitrago Santanilla, A. et al. P2Et phosphazene: a mild, functional group tolerant base for soluble, room temperature Pd-catalyzed C–N, C–O, and C–C cross-coupling reactions. Org. Lett. 17, 3370–3373 (2015).
Schneider, P. Schneider, G. De novo design at the edge of chaos. J. Med. Chem. 59, 4077–4086 (2016).
Ahneman, D. T., Estrada, J. G., Lin, S., Dreher, S. D. Doyle, A. G. Predicting reaction performance in C–N cross coupling using machine learning. Science 360, 186–190 (2018).
