Diversity-oriented synthesis as a tool for the discovery of novel biologically active small molecules

Natural products as sources of new drugs over the last 25 years

Newman, D. J., & Cragg, G. M. (2007) · Journal of Natural Products · doi:10.1021/np068054v · Cited by 5,517

Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success

Lovering, F., Bikker, J., & Humblet, C. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm901241e · Cited by 4,495

Target-Oriented and Diversity-Oriented Organic Synthesis in Drug Discovery

Schreiber, S. L. (2000) · Science · doi:10.1126/science.287.5460.1964 · Cited by 2,568

Drugs for bad bugs: confronting the challenges of antibacterial discovery

Payne, D. J., Gwynn, M. N., Holmes, D. J., & Pompliano, D. L. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2201 · Cited by 2,512

What is principal component analysis?

Ringnér, M. (2008) · Nature Biotechnology · doi:10.1038/nbt0308-303 · Cited by 2,407

A Planning Strategy for Diversity‐Oriented Synthesis

Burke, M. D., & Schreiber, S. L. (2004) · Angewandte Chemie International Edition · doi:10.1002/anie.200300626 · Cited by 1,493

A decade of fragment-based drug design: strategic advances and lessons learned

Hajduk, P. J., & Greer, J. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2220 · Cited by 1,064

Navigating chemical space for biology and medicine

Lipinski, C., & Hopkins, A. (2004) · Nature · doi:10.1038/nature03193 · Cited by 1,002

Antibacterial Natural Products in Medicinal Chemistry—Exodus or Revival?

von Nussbaum, F., Brands, M., Hinzen, B., Weigand, S., & Häbich, D. (2006) · Angewandte Chemie International Edition · doi:10.1002/anie.200600350 · Cited by 672

Molecular similarity: a key technique in molecular informatics

Bender, A., & Glen, R. C. (2004) · Organic & Biomolecular Chemistry · doi:10.1039/b409813g · Cited by 614

Diversity-oriented synthesis: Exploring the intersections between chemistry and biology

Tan, D. S. (2005) · Nature Chemical Biology · doi:10.1038/nchembio0705-74 · Cited by 605

Privileged Structures: Applications in Drug Discovery

DeSimone, R., Currie, K., Mitchell, S., Darrow, J., & Pippin, D. (2004) · Combinatorial Chemistry & High Throughput Screening · doi:10.2174/1386207043328544 · Cited by 577

Towards the Optimal Screening Collection: A Synthesis Strategy

Nielsen, T. E., & Schreiber, S. L. (2008) · Angewandte Chemie International Edition · doi:10.1002/anie.200703073 · Cited by 551

Charting biologically relevant chemical space: A structural classification of natural products (SCONP)

Koch, M. A., Schuffenhauer, A., Scheck, M., Wetzel, S., Casaulta, M., Odermatt, A., Ertl, P., & Waldmann, H. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503647102 · Cited by 544

Molecular Shape Diversity of Combinatorial Libraries: A Prerequisite for Broad Bioactivity

Sauer, W. H. B., & Schwarz, M. K. (2003) · Journal of Chemical Information and Computer Sciences · doi:10.1021/ci025599w · Cited by 498

Can we rationally design promiscuous drugs?

HOPKINS, A., MASON, J., & OVERINGTON, J. (2006) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2006.01.013 · Cited by 469

Generating Diverse Skeletons of Small Molecules Combinatorially

Burke, M. D., Berger, E. M., & Schreiber, S. L. (2003) · Science · doi:10.1126/science.1089946 · Cited by 375

Dissecting glucose signalling with diversity-oriented synthesis and small-molecule microarrays

Kuruvilla, F. G., Shamji, A. F., Sternson, S. M., Hergenrother, P. J., & Schreiber, S. L. (2002) · Nature · doi:10.1038/416653a · Cited by 367

Diversity-oriented synthesis; a challenge for synthetic chemistsElectronic supplementary information (ESI) available: Excel file of all the FDA new molecular entities between the years 1998 and July 2003, and new drug approvals between the years 1990 and 2002. See http://www.rsc.org/suppdata/ob/b3/b310752n/

Spring, D. R. (2003) · Organic & Biomolecular Chemistry · doi:10.1039/b310752n · Cited by 347

Discovery of protein phosphatase inhibitor classes by biology-oriented synthesis

Nören-Müller, A., Reis-Corrêa, I., Prinz, H., Rosenbaum, C., Saxena, K., Schwalbe, H. J., Vestweber, D., Cagna, G., Schunk, S., Schwarz, O., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601490103 · Cited by 303

Structural Diversity of Organic Chemistry. A Scaffold Analysis of the CAS Registry

Lipkus, A. H., Yuan, Q., Lucas, K. A., Funk, S. A., Bartelt, W. F., Schenck, R. J., & Trippe, A. J. (2008) · The Journal of Organic Chemistry · doi:10.1021/jo8001276 · Cited by 302

A small molecule that binds Hedgehog and blocks its signaling in human cells

Stanton, B. Z., Peng, L. F., Maloof, N., Nakai, K., Wang, X., Duffner, J. L., Taveras, K. M., Hyman, J. M., Lee, S. W., Koehler, A. N., et al. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.142 · Cited by 296

Chemical Genetics

Walsh, D. P., & Chang, Y.-T. (2006) · Chemical Reviews · doi:10.1021/cr0404141 · Cited by 296

Molecular diversity by design

Schreiber, S. L. (2009) · Nature · doi:10.1038/457153a · Cited by 292

Diversity-oriented synthesis; a spectrum of approaches and results

Spandl, R. J., Bender, A., & Spring, D. R. (2008) · Organic & Biomolecular Chemistry · doi:10.1039/b719372f · Cited by 281

Dominance of EMRSA-15 and -16 among MRSA causing nosocomial bacteraemia in the UK: analysis of isolates from the European Antimicrobial Resistance Surveillance System (EARSS)

Johnson, A. P. (2001) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/48.1.143 · Cited by 247

PERSPECTIVE: THE SMALL-MOLECULE APPROACH TO BIOLOGY

SCHREIBER (2003) · Chemical & Engineering News Archive · doi:10.1021/cen-v081n009.p051 · Cited by 246

Interactive exploration of chemical space with Scaffold Hunter

Wetzel, S., Klein, K., Renner, S., Rauh, D., Oprea, T. I., Mutzel, P., & Waldmann, H. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.187 · Cited by 228

Synthesis of Natural‐Product‐Like Molecules with Over Eighty Distinct Scaffolds

Morton, D., Leach, S., Cordier, C., Warriner, S., & Nelson, A. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200804486 · Cited by 224

Application of Combinatorial Chemistry Science on Modern Drug Discovery

Kennedy, J. P., Williams, L., Bridges, T. M., Daniels, R. N., Weaver, D., & Lindsley, C. W. (2008) · Journal of Combinatorial Chemistry · doi:10.1021/cc700187t · Cited by 213

A Synthesis Strategy Yielding Skeletally Diverse Small Molecules Combinatorially

Burke, M. D., Berger, E. M., & Schreiber, S. L. (2004) · Journal of the American Chemical Society · doi:10.1021/ja0457415 · Cited by 187

Fragment‐based Approaches in Drug Discovery

(2006) · Methods and Principles in Medicinal Chemistry · doi:10.1002/3527608761 · Cited by 181

Discovery of an Inhibitor of a Transcription Factor Using Small Molecule Microarrays and Diversity-Oriented Synthesis

Koehler, A. N., Shamji, A. F., & Schreiber, S. L. (2003) · Journal of the American Chemical Society · doi:10.1021/ja0352698 · Cited by 176

Current strategies for diversity-oriented synthesis

Dandapani, S., & Marcaurelle, L. A. (2010) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2010.03.018 · Cited by 170

Scaffold composition and biological relevance of screening libraries

Shelat, A. A., & Guy, R. K. (2007) · Nature Chemical Biology · doi:10.1038/nchembio0807-442 · Cited by 167

Diversity-Oriented Synthesis of Biaryl-Containing Medium Rings Using a One Bead/One Stock Solution Platform

Spring, D. R., Krishnan, S., Blackwell, H. E., & Schreiber, S. L. (2002) · Journal of the American Chemical Society · doi:10.1021/ja017248o · Cited by 165

Biology-inspired synthesis of compound libraries

Kaiser, M., Wetzel, S., Kumar, K., & Waldmann, H. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7492-1 · Cited by 148

Integration of fragment screening and library design

Siegal, G., Eiso, A. B., & Schultz, J. (2007) · Drug Discovery Today · doi:10.1016/j.drudis.2007.08.005 · Cited by 142

Bioactivity-guided mapping and navigation of chemical space

Renner, S., van Otterlo, W. A. L., Domínguez, M., Möcklinghoff, S., Hofmann, B., Wetzel, S., Schuffenhauer, A., Ertl, P., Oprea, T. I., Steinhilber, D., et al. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.188 · Cited by 140

Diversity‐oriented synthesis

Spandl, R. J., Díaz‐Gavilán, M., O’Connell, K. M. G., Thomas, G. L., & Spring, D. R. (2008) · The Chemical Record · doi:10.1002/tcr.20144 · Cited by 139

Anti‐MRSA Agent Discovery Using Diversity‐Oriented Synthesis

Thomas, G. L., Spandl, R. J., Glansdorp, F. G., Welch, M., Bender, A., Cockfield, J. D., Lindsay, J. A., Bryant, C. E., Brown, D. F. J., Loiseleur, O., et al. (2008) · Angewandte Chemie International Edition · doi:10.1002/anie.200705415 · Cited by 135

The discovery of antibacterial agents using diversity-oriented synthesis

Galloway, W. R. J. D., Bender, A., Welch, M., & Spring, D. R. (2009) · Chemical Communications · doi:10.1039/b816852k · Cited by 133

Properties and Architecture of Drugs and Natural Products Revisited

Grabowski, K., & Schneider, G. (2007) · Current Chemical Biology · doi:10.2174/2212796810701010115 · Cited by 132

Skeletal Diversity via a Folding Pathway: Synthesis of Indole Alkaloid-Like Skeletons

Oguri, H., & Schreiber, S. L. (2004) · Organic Letters · doi:10.1021/ol047945w · Cited by 122

Small Molecule Shape-Fingerprints

Haigh, J. A., Pickup, B. T., Grant, J., et al. (2005) · Journal of Chemical Information and Modeling · doi:10.1021/ci049651v · Cited by 116

On the potential of natural products in the discovery of pharma leads: A case for reassessment

Danishefsky, S. J. (2010) · Natural Product Reports · doi:10.1039/c003211p · Cited by 100

Chemical Genetics: Elucidating Biological Systems with Small-Molecule Compounds

Kawasumi, M., & Nghiem, P. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700853 · Cited by 96

Molecular characterisation of the dominant UK methicillin-resistant Staphylococcus aureus strains, EMRSA-15 and EMRSA-16

Moore, P. C. L., & Lindsay, J. A. (2002) · Journal of Medical Microbiology · doi:10.1099/0022-1317-51-6-516 · Cited by 95

Skeletal diversity construction via a branching synthetic strategy

Wyatt, E. E., Fergus, S., Galloway, W. R. J. D., Bender, A., Fox, D. J., Plowright, A. T., Jessiman, A. S., Welch, M., & Spring, D. R. (2006) · Chemical Communications · doi:10.1039/b607710b · Cited by 94

“Click, Click, Cyclize”: A DOS Approach to Sultams Utilizing Vinyl Sulfonamide Linchpins

Zhou, A., Rayabarapu, D. K., & Hanson, P. R. (2008) · Organic Letters · doi:10.1021/ol802467f · Cited by 84

An Oligomer-Based Approach to Skeletal Diversity in Small-Molecule Synthesis

Spiegel, D. A., Schroeder, F. C., Duvall, J. R., & Schreiber, S. L. (2006) · Journal of the American Chemical Society · doi:10.1021/ja065724a · Cited by 79

Synthesis of Diverse Lactam Carboxamides Leading to the Discovery of a New Transcription‐Factor Inhibitor

Ng, P. Y., Tang, Y., Knosp, W. M., Stadler, H. S., & Shaw, J. T. (2007) · Angewandte Chemie International Edition · doi:10.1002/anie.200700762 · Cited by 77

Synthetic Strategy toward Skeletal Diversity via Solid‐Supported, Otherwise Unstable Reactive Intermediates

Taylor, S. J., Taylor, A. M., & Schreiber, S. L. (2004) · Angewandte Chemie International Edition · doi:10.1002/anie.200353466 · Cited by 76

The principle of complementarity: chemical versus biological space

Haggarty, S. J. (2005) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2005.04.006 · Cited by 72

Assessment of structural diversity in combinatorial synthesis

Fergus, S., Bender, A., & Spring, D. R. (2005) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2005.03.004 · Cited by 61

Identification of an anti-MRSA dihydrofolate reductase inhibitor from a diversity-oriented synthesis

Wyatt, E. E., Galloway, W. R. J. D., Thomas, G. L., Welch, M., Loiseleur, O., Plowright, A. T., & Spring, D. R. (2008) · Chemical Communications · doi:10.1039/b812901k · Cited by 59

Synthesis of Unprecedented Scaffold Diversity

Galloway, W. R. J. D., Díaz‐Gavilán, M., Isidro‐Llobet, A., & Spring, D. R. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200805452 · Cited by 55

Stereochemical and Skeletal Diversity Arising from Amino Propargylic Alcohols

Pizzirani, D., Kaya, T., Clemons, P. A., & Schreiber, S. L. (2010) · Organic Letters · doi:10.1021/ol100914b · Cited by 55

The tert-Butylsulfinamide Lynchpin in Transition-Metal-Mediated Multiscaffold Library Synthesis

Bauer, R. A., DiBlasi, C. M., & Tan, D. S. (2010) · Organic Letters · doi:10.1021/ol100574y · Cited by 55

Fragment-based ligand discovery

Fischer, M. M., & Hubbard, R. E. (2009) · Molecular Interventions · doi:10.1124/mi.9.1.7 · Cited by 49

The State of the Art of Chemical Biology

Altmann, K., Büchner, J., Kessler, H., Diederich, F., Kräutler, B., Lippard, S. J., Liskamp, R. M. J., Müller, K., Nolan, E. M., Samorı̀, B., et al. (2008) · ChemBioChem · doi:10.1002/cbic.200800758 · Cited by 49

Gemmacin B: bringing diversity back into focus

Robinson, A., Thomas, G. L., Spandl, R. J., Welch, M., & Spring, D. R. (2008) · Organic & Biomolecular Chemistry · doi:10.1039/b809038f · Cited by 37

Aziridines as intermediates in diversity-oriented syntheses of alkaloids

Taylor, A. M., & Schreiber, S. L. (2009) · Tetrahedron Letters · doi:10.1016/j.tetlet.2009.02.034 · Cited by 36

What's in a number?

Drews, J. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2205 · Cited by 36

Identification of Lead Compounds As Antagonists of Protein Bcl-xL with a Diversity-Oriented Multidisciplinary Approach

Micco, S. D., Vitale, R., Pellecchia, M., Rega, M. F., Riva, R., Basso, A., & Bifulco, G. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm9010687 · Cited by 35

Enriching chemical space with diversity-oriented synthesis.

Thomas, G. L., Wyatt, E. E., & Spring, D. R. (2006) · PubMed · Cited by 35

Fragment-Based Approaches

Jahnke, W. (2007) · Elsevier eBooks · doi:10.1016/b0-08-045044-x/00114-0 · Cited by 12

Modulators of Protein–Protein Interactions

Milroy, L.-G., Grossmann, T. N., Hennig, S., Brunsveld, L., & Ottmann, C. (2014) · Chemical Reviews · doi:10.1021/cr400698c · Cited by 497

Catalytic Enantioselective Construction of Spiro Quaternary Carbon Stereocenters

Xu, P.-W., Yu, J.-S., Chen, C., Cao, Z.-Y., Zhou, F., & Zhou, J. (2019) · ACS Catalysis · doi:10.1021/acscatal.8b03694 · Cited by 325

State-of-the-art strategies for targeting protein–protein interactions by small-molecule inhibitors

Sheng, C., Dong, G., Miao, Z., Zhang, W., & Wang, W. (2015) · Chemical Society Reviews · doi:10.1039/c5cs00252d · Cited by 165

Targeting protein–protein interactions in hematologic malignancies: still a challenge or a great opportunity for future therapies?

Cierpicki, T., & Grembecka, J. (2015) · Immunological Reviews · doi:10.1111/imr.12244 · Cited by 53

Focused Libraries for Epigenetic Drug Discovery: The Importance of Isosteres: Miniperspective

Green, A. I., & Burslem, G. M. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00592 · Cited by 21