The many roles of molecular complexity in drug discovery

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

Lovering, F., Bikker, J. A., & Humblet, C. C. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm901241e · Cited by 4,507 · see citing works

DrugBank 4.0: shedding new light on drug metabolism

Law, V., Knox, C., Djoumbou-Feunang, Y., Jewison, T., Guo, A. C., Liu, Y., Maciejewski, A., Arndt, D., Wilson, M., Neveu, V., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1068 · Cited by 1,995 · see citing works

DataWarrior: An Open-Source Program For Chemistry Aware Data Visualization And Analysis

Sander, T., Freyss, J., von Korff, M., & Rufener, C. (2015) · Journal of Chemical Information and Modeling · doi:10.1021/ci500588j · Cited by 1,826 · see citing works

Escape from Flatland 2: complexity and promiscuity

Lovering, F. (2012) · MedChemComm · doi:10.1039/c2md20347b · Cited by 1,454 · see citing works

An analysis of the attrition of drug candidates from four major pharmaceutical companies

Waring, M. J., Arrowsmith, J., Leach, A. R., Leeson, P. D., Mandrell, S., Owen, R. M., Pairaudeau, G., Pennie, W. D., Pickett, S. D., Wang, J., et al. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4609 · Cited by 1,450 · see citing works

Handbook of Olfaction and Gustation

Doty, R. L. (2003) · CRC Press eBooks · doi:10.1201/9780203911457 · Cited by 1,228 · see citing works

Molecular Complexity and Its Impact on the Probability of Finding Leads for Drug Discovery

Hann, M. M., Leach, A. R., & Harper, G. (2001) · Journal of Chemical Information and Computer Sciences · doi:10.1021/ci000403i · Cited by 882 · see citing works

Molecular Similarity in Medicinal Chemistry

Maggiora, G. M., Vogt, M., Stumpfe, D., & Bajorath, J. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm401411z · Cited by 659 · see citing works

Polypharmacology: drug discovery for the future

Reddy, A. S., & Zhang, S. (2012) · Expert Review of Clinical Pharmacology · doi:10.1586/ecp.12.74 · Cited by 486 · see citing works

Analysis and comparison of 2D fingerprints: Insights into database screening performance using eight fingerprint methods

Duan, J., Dixon, S. L., Lowrie, J. F., & Sherman, W. (2010) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2010.05.008 · Cited by 445 · see citing works

The first general index of molecular complexity

Bertz, S. H. (1981) · Journal of the American Chemical Society · doi:10.1021/ja00402a071 · Cited by 439 · see citing works

Why do we need so many chemical similarity search methods?

Sheridan, R. (2002) · Drug Discovery Today · doi:10.1016/s1359-6446(02)02411-x · Cited by 412 · see citing works

Small molecules of different origins have distinct distributions of structural complexity that correlate with protein-binding profiles

Clemons, P. A., Bodycombe, N. E., Carrinski, H. A., Wilson, J. A., Shamji, A. F., Wagner, B. K., Koehler, A. N., & Schreiber, S. L. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012741107 · Cited by 343 · see citing works

Improving Drug Design: An Update on Recent Applications of Efficiency Metrics, Strategies for Replacing Problematic Elements, and Compounds in Nontraditional Drug Space

Meanwell, N. A. (2016) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.6b00043 · Cited by 244 · see citing works

Physicochemical Correlates of Olfactory Quality

Schiffman, S. S. (1974) · Science · doi:10.1126/science.185.4146.112 · Cited by 237 · see citing works

Recent Progress in Understanding Activity Cliffs and Their Utility in Medicinal Chemistry

Stumpfe, D., Hu, Y., Dimova, D., & Bajorath, J. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm401120g · Cited by 208 · see citing works

Grand Challenge Commentary: Accessing new chemical space for 'undruggable' targets

Dandapani, S., & Marcaurelle, L. A. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.479 · Cited by 206 · see citing works

An Additive Definition of Molecular Complexity

Böttcher, T. (2016) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5b00723 · Cited by 166 · see citing works

Computational Exploration of Molecular Scaffolds in Medicinal Chemistry

Hu, Y., Stumpfe, D., & Bajorath, J. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01746 · Cited by 158 · see citing works

Characterization of Activity Landscapes Using 2D and 3D Similarity Methods: Consensus Activity Cliffs

Medina‐Franco, J. L., Martínez‐Mayorga, K., Bender, A., Marín, R. M., Giulianotti, M. A., Pinilla, C., & Houghten, R. A. (2009) · Journal of Chemical Information and Modeling · doi:10.1021/ci800379q · Cited by 152 · see citing works

Expanding the medicinally relevant chemical space with compound libraries

López-Vallejo, F., Giulianotti, M. A., Houghten, R. A., & Medina‐Franco, J. L. (2012) · Drug Discovery Today · doi:10.1016/j.drudis.2012.04.001 · Cited by 134 · see citing works

Molecular complexity: a simplified formula adapted to individual atoms

Hendrickson, J. B., Huang, P., & Toczko, A. G. (1987) · Journal of Chemical Information and Computer Sciences · doi:10.1021/ci00054a004 · Cited by 132 · see citing works

Molecular complexity determines the number of olfactory notes and the pleasantness of smells

Kermen, F., Chakirian, A., Sezille, C., Joussain, P., Goff, G. L., Ziessel, A., Chastrette, M., Mandairon, N., Didier, A., Rouby, C., et al. (2011) · Scientific Reports · doi:10.1038/srep00206 · Cited by 119 · see citing works

Search for all self-avoiding paths for molecular graphs

Randić, M., Brissey, G. M., Spencer, R. B., & Wilkins, C. L. (1979) · Computers & Chemistry · doi:10.1016/0097-8485(79)80002-9 · Cited by 117 · see citing works

Relationships between Molecular Complexity, Biological Activity, and Structural Diversity

Schuffenhauer, A., Brown, N., Selzer, P. M., Ertl, P., & Jacoby, E. (2005) · Journal of Chemical Information and Modeling · doi:10.1021/ci0503558 · Cited by 102 · see citing works

How Diverse Are Diversity Assessment Methods? A Comparative Analysis and Benchmarking of Molecular Descriptor Space

Koutsoukas, A., Paricharak, S., Galloway, W. R. J. D., Spring, D. R., IJzerman, A. P., Glen, R. C., Marcus, D., & Bender, A. (2013) · Journal of Chemical Information and Modeling · doi:10.1021/ci400469u · Cited by 88 · see citing works

A New and Simple Approach to Chemical Complexity. Application to the Synthesis of Natural Products

Barone, R., & Chanon, M. (2001) · Journal of Chemical Information and Computer Sciences · doi:10.1021/ci000145p · Cited by 87 · see citing works

Rapid Evaluation of Synthetic and Molecular Complexity for in Silico Chemistry

Allu, T. K., & Oprea, T. I. (2005) · Journal of Chemical Information and Modeling · doi:10.1021/ci0501387 · Cited by 87 · see citing works

Modeling a Crowdsourced Definition of Molecular Complexity

Sheridan, R. P., Zorn, N., Sherer, E. C., Campeau, L., Chang, C., Cumming, J. N., Maddess, M. L., Nantermet, P. G., Sinz, C. J., & O’Shea, P. D. (2014) · Journal of Chemical Information and Modeling · doi:10.1021/ci5001778 · Cited by 80 · see citing works

Complex molecules: do they add value?

Selzer, P. M., ROTH, H. ‐., Ertl, P., & Schuffenhauer, A. (2005) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2005.04.001 · Cited by 75 · see citing works

On the Structure of Total Synthesis of Complex Natural Products

WHITLOCK, H. W. J. (1998) · The Journal of Organic Chemistry · doi:10.1021/jo9814546 · Cited by 74 · see citing works

Investigation of the Relationship between Topology and Selectivity for Druglike Molecules

Yang, Y., Chen, H., Nilsson, I., Mureşan, S., & Engkvist, O. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm1008456 · Cited by 63 · see citing works

SAR Exploration Guided by LE and Fsp 3 : Discovery of a Selective and Orally Efficacious RORγ Inhibitor

Hirata, K., Kotoku, M., Seki, N., Maeba, T., Maeda, K., Hirashima, S., Sakai, T., Obika, S., Hori, A., Hase, Y., et al. (2015) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.5b00253 · Cited by 62 · see citing works

Walk Counts, Labyrinthicity, and Complexity of Acyclic and Cyclic Graphs and Molecules

Rücker, G., & Rücker, C. (1999) · Journal of Chemical Information and Computer Sciences · doi:10.1021/ci9900579 · Cited by 61 · see citing works

Overall Connectivities/Topological Complexities: A New Powerful Tool for QSPR/QSAR

Bonchev, D. (2000) · Journal of Chemical Information and Computer Sciences · doi:10.1021/ci990120u · Cited by 59 · see citing works

Chemoinformatic Expedition of the Chemical Space of Fungal Products

González-Medina, M., Prieto-Martínez, F. D., Naveja, J. J., Méndez‐Lucio, O., El‐Elimat, T., Pearce, C. J., Oberlies, N. H., Figueroa, M., & Medina‐Franco, J. L. (2016) · Future Medicinal Chemistry · doi:10.4155/fmc-2016-0079 · Cited by 46 · see citing works

Complexity of Molecules

Nikolić, S., Trinajstić, N., & Tolić, I. M. (2000) · Journal of Chemical Information and Computer Sciences · doi:10.1021/ci9901183 · Cited by 37 · see citing works

Characterization of molecular complexity

Randić, M., & Plavšić, D. (2002) · International Journal of Quantum Chemistry · doi:10.1002/qua.10343 · Cited by 35 · see citing works

On the concept of molecular complexity

Randić, M., & Plavšić, D. (2002) · Institutional Repository of the Ruđer Bošković Institute (Ruđer Bošković Institute) · Cited by 33 · see citing works

How Promiscuous Are Pharmaceutically Relevant Compounds? A Data-Driven Assessment

Hu, Y., & Bajorath, J. (2012) · The AAPS Journal · doi:10.1208/s12248-012-9421-y · Cited by 33 · see citing works

Dependence of odor intensity on the hydrophobic properties of molecules. A quantitative structure odor intensity relationship

Greenberg, M. J. (1979) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf60222a054 · Cited by 28 · see citing works

Method for the Evaluation of Structure–Activity Relationship Information Associated with Coordinated Activity Cliffs

Dimova, D., Stumpfe, D., & Bajorath, J. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500577n · Cited by 18 · see citing works

Quantum-chemical quantification of molecular complexity and chirality

Luzanov, A. V., & Babich, E. N. (1995) · Journal of Molecular Structure THEOCHEM · doi:10.1016/0166-1280(94)03944-g · Cited by 14 · see citing works

About Complexity and Self-Similarity of Chemical Structures in Drug Discovery

von Korff, M., & Sander, T. (2012) · Springer eBooks · doi:10.1007/978-3-642-33914-1_39 · Cited by 10 · see citing works

Chaos and complex systems : proceedings of the 4th International Interdisciplinary Chaos Symposium

Stavrinides, S. G. (2013) · doi:10.1007/978-3-642-33914-1 · Cited by 3 · see citing works

Current Contributions of Organofluorine Compounds to the Agrochemical Industry

Ogawa, Y., Tokunaga, E., Kobayashi, O., Hirai, K., & Shibata, N. (2020) · iScience · doi:10.1016/j.isci.2020.101467 · Cited by 1,253 · see citing works

QSAR without borders

Muratov, E. N., Bajorath, J., Sheridan, R. P., Tetko, I. V., Filimonov, D., Poroikov, V., Oprea, T. I., Baskin, I. I., Varnek, A., Roitberg, A., et al. (2020) · Chemical Society Reviews · doi:10.1039/d0cs00098a · Cited by 913 · see citing works

Transition-Metal-Catalyzed C–H Bond Activation for the Formation of C–C Bonds in Complex Molecules

Docherty, J. H., Lister, T. M., McArthur, G., Findlay, M. T., Domingo‐Legarda, P., Kenyon, J., Choudhary, S., & Larrosa, I. (2023) · Chemical Reviews · doi:10.1021/acs.chemrev.2c00888 · Cited by 603 · see citing works

IMPPAT 2.0: An Enhanced and Expanded Phytochemical Atlas of Indian Medicinal Plants

Vivek-Ananth, R. P., Mohanraj, K., Sahoo, A. K., & Samal, A. (2023) · ACS Omega · doi:10.1021/acsomega.3c00156 · Cited by 410 · see citing works

SCScore: Synthetic Complexity Learned from a Reaction Corpus

Coley, C. W., Rogers, L., Green, W. H., & Jensen, K. F. (2018) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.7b00622 · Cited by 381 · see citing works

Structural Simplification of Natural Products

Wang, S., Dong, G., & Sheng, C. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00504 · Cited by 262 · see citing works

Antibacterial activities with the structure-activity relationship of coumarin derivatives

Qin, H., Zhang, Z.-W., Lekkala, R., & Rakesh, K. P. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112832 · Cited by 240 · see citing works

The Symbiotic Relationship Between Drug Discovery and Organic Chemistry

Grygorenko, O. O., Volochnyuk, D. M., Ryabukhin, S. V., & Judd, D. B. (2019) · Chemistry - A European Journal · doi:10.1002/chem.201903232 · Cited by 172 · see citing works

SYBA: Bayesian estimation of synthetic accessibility of organic compounds

Voršilák, M., Kolář, M., Čmelo, I., & Svozil, D. (2020) · Journal of Cheminformatics · doi:10.1186/s13321-020-00439-2 · Cited by 152 · see citing works

Tunable molecular editing of indoles with fluoroalkyl carbenes

Liu, S., Yang, Y., Song, Q., Liu, Z., Lu, Y. H., Wang, Z., Sivaguru, P., & Bi, X. (2024) · Nature Chemistry · doi:10.1038/s41557-024-01468-2 · Cited by 141 · see citing works

Emerging Building Blocks for Medicinal Chemistry: Recent Synthetic Advances

Grygorenko, O. O., Volochnyuk, D. M., & Vashchenko, B. V. (2021) · European Journal of Organic Chemistry · doi:10.1002/ejoc.202100857 · Cited by 129 · see citing works

Oxetanes in Drug Discovery Campaigns

Rojas, J. J., & Bull, J. A. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c01101 · Cited by 125 · see citing works

Molecular Complexity as a Driver for Chemical Process Innovation in the Pharmaceutical Industry

Caille, S., Cui, S., Faul, M. M., Mennen, S. M., Tedrow, J. S., & Walker, S. D. (2019) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.9b00735 · Cited by 108 · see citing works

Medicinal chemistry in drug discovery in big pharma: past, present and future

Campbell, I. B., Macdonald, S. J. F., & Procopiou, P. A. (2017) · Drug Discovery Today · doi:10.1016/j.drudis.2017.10.007 · Cited by 103 · see citing works

Trends in small molecule drug properties: A developability molecule assessment perspective

Agarwal, P., Huckle, J. E., Newman, J., & Reid, D. L. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.103366 · Cited by 96 · see citing works

Structural simplification: an efficient strategy in lead optimization

Wang, S., Dong, G., & Sheng, C. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.05.004 · Cited by 94 · see citing works

Developing hybrid molecule therapeutics for diverse enzyme inhibitory action: Active role of coumarin-based structural leads in drug discovery

Ibrar, A., Shehzadi, S. A., Saeed, F., & Khan, I. A. (2018) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2018.05.042 · Cited by 93 · see citing works

Stereochemical diversity as a source of discovery in chemical biology

Scott, K. A., Ropek, N., Melillo, B. N., Schreiber, S. L., Cravatt, B. F., & Vinogradova, E. V. (2022) · Current Research in Chemical Biology · doi:10.1016/j.crchbi.2022.100028 · Cited by 83 · see citing works

Spacial Score─A Comprehensive Topological Indicator for Small-Molecule Complexity

Krzyzanowski, A., Pahl, A., Grigalunas, M., & Waldmann, H. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00689 · Cited by 83 · see citing works

Biocatalytic routes to anti-viral agents and their synthetic intermediates

Slagman, S., & Fessner, W. (2020) · Chemical Society Reviews · doi:10.1039/d0cs00763c · Cited by 78 · see citing works

Multicomponent reactions (MCRs) yielding medicinally relevant rings: a recent update and chemical space analysis of the scaffolds

Tandi, M., Sharma, V., Gopal, B., & Sundriyal, S. (2025) · RSC Advances · doi:10.1039/d4ra06681b · Cited by 80 · see citing works

Cheminformatics to Characterize Pharmacologically Active Natural Products

Medina‐Franco, J. L., & Saldívar‐González, F. I. (2020) · Biomolecules · doi:10.3390/biom10111566 · Cited by 79 · see citing works

Catalytic Intermolecular Asymmetric [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes: Practical Synthesis of Enantioenriched Highly Substituted Bicyclo[2.1.1]hexanes

Li, Y.-J., Wu, Z.-L., Gu, Q., Fan, T., Duan, M.-H., Wu, L., Wang, Y., Wu, J.-P., Fu, F.-L., Sang, F., et al. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.4c10968 · Cited by 74 · see citing works

Progress on open chemoinformatic tools for expanding and exploring the chemical space

Medina‐Franco, J. L., Sánchez‐Cruz, N., López‐López, E., & Díaz‐Eufracio, B. I. (2021) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-021-00399-1 · Cited by 68 · see citing works

Analysis of a large food chemical database: chemical space, diversity, and complexity

Naveja, J. J., Rico‐Hidalgo, M. P., & Medina‐Franco, J. L. (2018) · F1000Research · doi:10.12688/f1000research.15440.2 · Cited by 68 · see citing works

Chemical Space and Diversity of the NuBBE Database: A Chemoinformatic Characterization

Saldívar‐González, F. I., Valli, M., Andricopulo, A. D., Bolzani, V. D. S., & Medina‐Franco, J. L. (2018) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.8b00619 · Cited by 66 · see citing works

Discovery of Elironrasib (RMC-6291), a Potent and Orally Bioavailable, RAS(ON) G12C-Selective, Covalent Tricomplex Inhibitor for the Treatment of Patients with RAS G12C-Addicted Cancers

Cregg, J., Pota, K., Tomlinson, A. C. A., Yano, J. K., Marquez, A., Liu, Y., Schulze, C. J., Seamon, K. J., Holderfield, M. T., Wei, X., et al. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c02313 · Cited by 67 · see citing works

Synergistic Effects of Stereochemistry and Appendages on the Performance Diversity of a Collection of Synthetic Compounds

Melillo, B. N., Zoller, J., Hua, B. K., Verho, O., Borghs, J. C., Nelson, S. D., Maetani, M., Wawer, M. J., Clemons, P. A., & Schreiber, S. L. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b07319 · Cited by 61 · see citing works

Molecular complexity as a driving force for the advancement of organic synthesis

Wright, B. A., & Sarpong, R. (2024) · Nature Reviews Chemistry · doi:10.1038/s41570-024-00645-8 · Cited by 67 · see citing works

Can easy chemistry produce complex, diverse, and novel molecules?

Tomberg, A., & Boström, J. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.09.027 · Cited by 59 · see citing works

Discovery of a Janus Kinase Inhibitor Bearing a Highly Three-Dimensional Spiro Scaffold: JTE-052 (Delgocitinib) as a New Dermatological Agent to Treat Inflammatory Skin Disorders

Noji, S., Hara, Y., Miura, T., Yamanaka, H., Maeda, K., Hori, A., Yamamoto, H., Obika, S., Inoue, M., Hase, Y., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00450 · Cited by 59 · see citing works

Platform for Unified Molecular Analysis: PUMA

González-Medina, M., & Medina‐Franco, J. L. (2017) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.7b00253 · Cited by 56 · see citing works

Understanding the chemodiversity of plants: Quantification, variation and ecological function

Petrén, H., Anaia, R. A., Aragam, K. S., Bräutigam, A., Eckert, S., Heinen, R., Jakobs, R., Ojeda‐Prieto, L., Popp, M., Sasidharan, R., et al. (2024) · Ecological Monographs · doi:10.1002/ecm.1635 · Cited by 55 · see citing works

Doubly stereoconvergent crystallization enabled by asymmetric catalysis

Cruz, P. D. J., Cassels, W. R., Chen, C., & Johnson, J. S. (2022) · Science · doi:10.1126/science.abo5048 · Cited by 51 · see citing works

Structure-based drug repositioning over the human TMPRSS2 protease domain: search for chemical probes able to repress SARS-CoV-2 Spike protein cleavages

Singh, N., Decroly, É., Khatib, A., & Villoutreix, B. O. (2020) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2020.105495 · Cited by 50 · see citing works

Finding the Missing Property Concepts in Pesticide-Likeness

Chen, D., Hao, G., & Song, B. (2022) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.2c02757 · Cited by 45 · see citing works

Step-Economical Photoassisted Diversity-Oriented Synthesis: Sustaining Cascade Photoreactions in Oxalyl Anilides to Access Complex Polyheterocyclic Molecular Architectures

Kuznetsov, D. M., & Kutateladze, A. G. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b07598 · Cited by 43 · see citing works

The Conformational Contribution to Molecular Complexity and Its Implications for Information Processing in Living Beings and Chemical Artificial Intelligence

Gentili, P. L. (2024) · Biomimetics · doi:10.3390/biomimetics9020121 · Cited by 42 · see citing works

Novel poly (2-oxazoline) block copolymer with aromatic heterocyclic side chains as a drug delivery platform

Hwang, D., Ramsey, J. D., Makita, N., Sachse, C., Jordan, R., Sokolsky-Papkov, M., & Kabanov, A. V. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.06.037 · Cited by 40 · see citing works

DiaNat-DB: a molecular database of antidiabetic compounds from medicinal plants

Madariaga‐Mazón, A., Naveja, J. J., Medina‐Franco, J. L., Noriega-Colima, K. O., & Martínez‐Mayorga, K. (2021) · RSC Advances · doi:10.1039/d0ra10453a · Cited by 41 · see citing works

Analysis of a large food chemical database: chemical space, diversity, and complexity

Naveja, J. J., Rico‐Hidalgo, M. P., & Medina‐Franco, J. L. (2018) · F1000Research · doi:10.12688/f1000research.15440.1 · Cited by 40 · see citing works

Insights from pharmacological similarity of epigenetic targets in epipolypharmacology

Naveja, J. J., & Medina‐Franco, J. L. (2017) · Drug Discovery Today · doi:10.1016/j.drudis.2017.10.006 · Cited by 33 · see citing works

A Fragment Library of Natural Products and its Comparative Chemoinformatic Characterization

Chávez‐Hernández, A. L., Sánchez‐Cruz, N., & Medina‐Franco, J. L. (2020) · Molecular Informatics · doi:10.1002/minf.202000050 · Cited by 35 · see citing works

A New Organocatalytic Desymmetrization Reaction Enables the Enantioselective Total Synthesis of Madangamine E

Shiomi, S., Shennan, B. D. A., Yamazaki, K., de Arriba, A. L. F., Vasu, D., Hamlin, T. A., & Dixon, D. J. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.1c12040 · Cited by 35 · see citing works

Palladium-Catalyzed Annulations via Sequential C–H Activations of C(sp2)–H/C(sp3)–H or C(sp3)–H/C(sp3)–H Bonds

Wei, W., Czajkowski, M., Kuang, Y., Nguyen, T.-A. V., Qin, B., & Tomanik, M. (2024) · ACS Catalysis · doi:10.1021/acscatal.4c01243 · Cited by 34 · see citing works

Information entropy changes in chemical reactions

Sabirov, D. S. (2017) · Computational and Theoretical Chemistry · doi:10.1016/j.comptc.2017.11.022 · Cited by 34 · see citing works

Cheminformatic characterization of natural products from Panama

Olmedo, D. A., González-Medina, M., Gupta, M. P., & Medina‐Franco, J. L. (2017) · Molecular Diversity · doi:10.1007/s11030-017-9781-4 · Cited by 35 · see citing works

Synergistic Brønsted/Lewis acid catalyzed aromatic alkylation with unactivated tertiary alcohols or di- tert -butylperoxide to synthesize quaternary carbon centers

Pan, A., Chojnacka, M., Crowley, R., Göttemann, L., Haines, B. E., & Kou, K. G. M. (2022) · Chemical Science · doi:10.1039/d1sc06422c · Cited by 32 · see citing works

Copper‐Catalyzed Enantioselective Skeletal Editing through a Formal Nitrogen Insertion into Indoles to Synthesize Atropisomeric Aminoaryl Quinoxalines

Zhang, X., Zhang, J.-Q., Sun, Z., Shan, H.-M., Su, J., Ma, X., Su, G., Xu, L., & Mo, D. (2024) · Angewandte Chemie International Edition · doi:10.1002/anie.202420390 · Cited by 31 · see citing works

Roles of Virtual Screening and Molecular Dynamics Simulations in Discovering and Understanding Antimalarial Drugs

Duay, S. S., Yap, R. C. Y., Gaitano, A. L., Santos, J. A. A., & Macalino, S. J. Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119289 · Cited by 31 · see citing works

Molecular Complexity: You Know It When You See It

Oprea, T. I., & Bologa, C. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c01507 · Cited by 31 · see citing works

Molecular Connectivity Predefines Polypharmacology: Aliphatic Rings, Chirality, and sp3 Centers Enhance Target Selectivity

Monteleone, S., Fuchs, J. E., & Liedl, K. R. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00552 · Cited by 29 · see citing works

Scope of 3D Shape-Based Approaches in Predicting the Macromolecular Targets of Structurally Complex Small Molecules Including Natural Products and Macrocyclic Ligands

Chen, Y., Mathai, N., & Kirchmair, J. (2020) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c00161 · Cited by 29 · see citing works

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Serafini, M. T., Cargnin, S., Massarotti, A., Tron, G. C., Pirali, T., & Genazzani, A. A. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00181 · Cited by 29 · see citing works

Investigating and Quantifying Molecular Complexity Using Assembly Theory and Spectroscopy

Jirásek, M., Sharma, A., Bame, J. R., Mehr, S. H. M., Bell, N. L., Marshall, S., Mathis, C., Macleod, A., Cooper, G. J. T., Swart, M., et al. (2024) · ACS Central Science · doi:10.1021/acscentsci.4c00120 · Cited by 32 · see citing works

Hydrosoluble and Liposoluble Vitamins: New Perspectives through ADMET Analysis

Nicolov, M. F., Cocora, M., Buda, V. O., Danciu, C., Dușe, A. O., Watz, C. G., & Borcan, F. (2021) · Medicina · doi:10.3390/medicina57111204 · Cited by 26 · see citing works

One‐Pot Sequential Photoredox Chemistry and Asymmetric Transfer Hydrogenation with a Single Catalyst

Zhang, X., Qin, J., Huang, X., & Meggers, E. (2018) · European Journal of Organic Chemistry · doi:10.1002/ejoc.201701652 · Cited by 25 · see citing works

Physicochemical and Structural Parameters Contributing to the Antibacterial Activity and Efflux Susceptibility of Small-Molecule Inhibitors of Escherichia coli

Zahed, S. S. E., French, S., Farha, M. A., Kumar, G., & Brown, E. D. (2021) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01925-20 · Cited by 25 · see citing works

Saturated Heterocyclic Aminosulfonyl Fluorides: New Scaffolds for Protecting‐Group‐Free Synthesis of Sulfonamides

Zhersh, S., Blahun, O. P., Sadkova, I. V., Tolmachev, A. A., Moroz, Y. S., & Mykhailiuk, P. K. (2018) · Chemistry - A European Journal · doi:10.1002/chem.201801140 · Cited by 23 · see citing works

In‐depth insight into the methods of plasma protein‐drug interaction studies: Comparison of capillary electrophoresis‐frontal analysis, isothermal titration calorimetry, circular dichroism and equilibrium dialysis

Nevídalová, H., Michalcová, L., & Glatz, Z. (2017) · Electrophoresis · doi:10.1002/elps.201700325 · Cited by 22 · see citing works

AI-Driven Chemical Design: Transforming the Sustainability of the Pharmaceutical Industry

Ruiz-Gonzalez, A. (2025) · Future Pharmacology · doi:10.3390/futurepharmacol5020024 · Cited by 23 · see citing works

Stereodivergent Complexity-to-Diversity Strategy en Route to the Synthesis of Nature-Inspired Skeleta

Srinivasulu, V., Srikanth, G., Khanfar, M. A., Abu‐Yousef, I. A., Majdalawieh, A. F., Mazitschek, R., Setty, S. C., Sebastian, A., & Al‐Tel, T. H. (2022) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.1c02698 · Cited by 19 · see citing works

(3 + 2) Cycloaddition Reaction of the Endocyclic N-Silyl Enamine and N,N′-Cyclic Azomethine Imine

Cao, V. D., Kim, H., Kwak, J., & Joung, S. (2022) · Organic Letters · doi:10.1021/acs.orglett.2c00366 · Cited by 19 · see citing works

Novel Pyran-Linked Phthalazinone-Pyrazole Hybrids: Synthesis, Cytotoxicity Evaluation, Molecular Modeling, and Descriptor Studies

Malik, M. S., Asghar, B. H., Syed, R., Alsantali, R. I., Morad, M. H., Altass, H. M., Moussa, Z., Althagafi, I. I., Jassas, R. S., & Ahmed, S. A. (2021) · Frontiers in Chemistry · doi:10.3389/fchem.2021.666573 · Cited by 17 · see citing works

Enhancing the efficiency of the ruthenium catalysts in the reductive amination without an external hydrogen source

Fatkulin, A. R., Afanasyev, O. I., Tsygankov, A. A., & Chusov, D. A. (2021) · Journal of Catalysis · doi:10.1016/j.jcat.2021.12.018 · Cited by 17 · see citing works

Do Fragments and Crystallization Additives Bind Similarly to Drug-like Ligands?

Drwal, M. N., Jacquemard, C., Perez, C. A., Desaphy, J., & Kellenberger, E. (2017) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.6b00769 · Cited by 17 · see citing works

Stereoselective Late-Stage Transformations of Indolo[2,3-a]quinolizines Skeleta to Nature-Inspired Scaffolds

Srinivasulu, V., Sieburth, S. M., Khanfar, M. A., Abu‐Yousef, I. A., Majdalawieh, A. F., Ramanathan, M., Sebastian, A., & Al‐Tel, T. H. (2021) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.1c01523 · Cited by 16 · see citing works

Discovery of indolizine lactones as anticancer agents and their optimization through late-stage functionalization

da Silva, T. S., Souza, M. S., Andricopulo, A. D., & Coelho, F. (2023) · RSC Advances · doi:10.1039/d3ra03395c · Cited by 16 · see citing works

Chemoinformatics approaches to assess chemical diversity and complexity of small molecules

Saldívar‐González, F. I., & Medina‐Franco, J. L. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818349-6.00003-0 · Cited by 16 · see citing works

Chemical Multiverse and Diversity of Food Chemicals

Avellaneda-Tamayo, J. F., Chávez‐Hernández, A. L., Prado‐Romero, D. L., & Medina‐Franco, J. L. (2024) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.3c01617 · Cited by 15 · see citing works

Artificial Intelligence in Compound Design

Grebner, C., Matter, H., & Heßler, G. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1787-8_15 · Cited by 17 · see citing works

Synthetic Matching of Complex Monoterpene Indole Alkaloid Chemical Space

Xie, J., Pahl, A., Krzyzanowski, A., Krupp, A., Liu, J., Koska, S., Schölermann, B., Zhang, R., Bonowski, J., Sievers, S., et al. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202310222 · Cited by 13 · see citing works

Chemoinformatic Approach: The Case of Natural Products of Panama

Olmedo, D. A., & Medina‐Franco, J. L. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.87779 · Cited by 14 · see citing works

Comparative analysis of FDA approvals by top 20 pharma companies (2014–2023)

Schuhmacher, A., Gassmann, O., Hinder, M., & Hartl, D. (2024) · Drug Discovery Today · doi:10.1016/j.drudis.2024.104128 · Cited by 11 · see citing works

A View on Molecular Complexity from the GDB Chemical Space

Buehler, Y., & Reymond, J. (2025) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5c00334 · Cited by 13 · see citing works

Carbon monoxide-driven osmium catalyzed reductive amination harvesting WGSR power

Biriukov, K. O., Vinogradov, M. M., Afanasyev, O. I., Vasilyev, D., Tsygankov, A. A., Godovikova, M. I., Nelyubina, Y. V., Loginov, D. A., & Chusov, D. A. (2021) · Catalysis Science & Technology · doi:10.1039/d1cy00695a · Cited by 11 · see citing works

Maximizing Step‐Normalized Increases in Molecular Complexity: Formal [4+2+2+2] Photoinduced Cyclization Cascade to Access Polyheterocycles Possessing Privileged Substructures

Reddy, D. S., Novitskiy, I. M., & Kutateladze, A. G. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202112573 · Cited by 11 · see citing works

An Analysis of Published Synthetic Routes, Route Targets, and Reaction Types (2000–2020)

Genheden, S., & Howell, G. P. (2024) · Organic Process Research & Development · doi:10.1021/acs.oprd.4c00389 · Cited by 9 · see citing works

Performance analysis of activation functions in molecular property prediction using Message Passing Graph Neural Networks

Chanana, G. (2025) · Chemical Physics · doi:10.1016/j.chemphys.2024.112591 · Cited by 9 · see citing works

Latin American databases of natural products: biodiversity and drug discovery against SARS-CoV-2

Nuñez, M. J., Díaz‐Eufracio, B. I., Medina‐Franco, J. L., & Olmedo, D. A. (2021) · RSC Advances · doi:10.1039/d1ra01507a · Cited by 9 · see citing works

Neglected Tropical Diseases: A Chemoinformatics Approach for the Use of Biodiversity in Anti-Trypanosomatid Drug Discovery

Valli, M., Doring, T. H., Marx, E., Ferreira, L. L. G., Medina‐Franco, J. L., & Andricopulo, A. D. (2024) · Biomolecules · doi:10.3390/biom14081033 · Cited by 9 · see citing works

Enantio- and Diastereoselective Mannich Reactions of ß-Dicarbonyls by Second Stage Diastereoconvergent Crystallization

Cassels, W. R., Crawford, E. T., & Johnson, J. S. (2023) · ACS Catalysis · doi:10.1021/acscatal.3c01515 · Cited by 9 · see citing works

Catalytic sp3–sp3 Functionalisation of Sulfonamides: Late‐Stage Modification of Drug‐Like Molecules

Abdulla, O., Clayton, A. D., Faulkner, R. A., Gill, D. M., Rice, C. R., Walton, S. M., & Sweeney, J. B. (2016) · Chemistry - A European Journal · doi:10.1002/chem.201605464 · Cited by 9 · see citing works

Digitization of molecular complexity with machine learning

Tyrin, A. S., Boiko, D. A., Kolomoets, N. I., & Ananikov, V. P. (2025) · Chemical Science · doi:10.1039/d4sc07320g · Cited by 11 · see citing works

Visible-Light-Mediated aza Paternò–Büchi Reactions and Related Cycloadditions for the Formation of Azetidines and Azetines

Ng, C. H., & Schindler, C. S. (2026) · Accounts of Chemical Research · doi:10.1021/acs.accounts.5c00914 · Cited by 8 · see citing works

Assembly theory and its relationship with computational complexity

Kempes, C. P., Lachmann, M., Iannaccone, A., Fricke, G. M., Chowdhury, M. R., Walker, S. I., & Cronin, L. (2025) · npj Complexity · doi:10.1038/s44260-025-00049-9 · Cited by 11 · see citing works

Accelerating Pharmaceutical Development via Metal‐Mediated Bond Formation

Borths, C. J., & Walker, S. D. (2020) · Israel Journal of Chemistry · doi:10.1002/ijch.201900176 · Cited by 8 · see citing works

Cheminformatics analysis of molecular datasets of transcription factors associated with quorum sensing in Pseudomonas aeruginosa

Victoria-Muñoz, F., Sánchez‐Cruz, N., Medina‐Franco, J. L., & López-Vallejo, F. (2022) · RSC Advances · doi:10.1039/d1ra08352j · Cited by 8 · see citing works

Harnessing C–O Bonds in Stereoselective Cross-Coupling and Cross-Electrophile Coupling Reactions

Jarvo, E. R., & Sanford, A. B. (2020) · Synlett · doi:10.1055/s-0040-1705987 · Cited by 8 · see citing works

Phosphine ligands in the ruthenium-catalyzed reductive amination without an external hydrogen source

Makarova, M., Afanasyev, O. I., Kliuev, F. S., Nelyubina, Y. V., Godovikova, M. I., & Chusov, D. A. (2021) · Journal of Organometallic Chemistry · doi:10.1016/j.jorganchem.2021.121806 · Cited by 8 · see citing works

Measuring Molecular Complexity

Slocombe, L., & Walker, S. I. (2024) · ACS Central Science · doi:10.1021/acscentsci.4c00697 · Cited by 8 · see citing works

Two-Component versus Three-Component Condensations in the Race between Hydrazide, Triketone, and Hydrogen Peroxide-How do All Six Reactive Centers Cooperate to Incorporate the Most Diverse Set of Heteroatomic Bridges in a Tricyclic Frame?

Yaremenko, I. A., Belyakova, Y. Y., Radulov, P. S., Medvedev, M. G., Krivoshchapov, N. V., Alabugin, I. V., & Terent'ev, A. O. (2023) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.3c01415 · Cited by 7 · see citing works

Chemoinformatic Characterization of NAPROC-13: A Database for Natural Product 13 C NMR Dereplication

Avellaneda-Tamayo, J. F., Agudo-Muñoz, N. A., Sánchez-Galán, J. E., López‐Pérez, J. L., & Medina‐Franco, J. L. (2024) · Journal of Natural Products · doi:10.1021/acs.jnatprod.4c00530 · Cited by 7 · see citing works

Copper(I)-Catalyzed Skeletal Rearrangement-Driven Cycloisomerization of 1,11-Diynes

Zhang, J.-Q., Li, Q., Chen, S.-L., Li, H., Chen, C., Zhong, X., & Mo, D. (2025) · Organic Letters · doi:10.1021/acs.orglett.5c02326 · Cited by 7 · see citing works

Broad assessment of bioactivity of a collection of spiroindane pyrrolidines through “cell painting”

Singh, M. P., Garza, N., Pearson, Z., Douglas, J. T., & Bošković, Ž. (2020) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2020.115547 · Cited by 8 · see citing works

Visible-Light-Induced Synthesis of Imidazolidines Through Formal [3+2] Cycloaddition of Aromatic Imines with N,N,N',N'-Tetramethyldiaminomethane

Itoh, K., Ishii, N., Takashino, A., Hara, A., Kon, S., Mizuguchi, T., Karaki, F., Hirayama, S., Shibagaki, Y., Nagai, K., et al. (2022) · Journal of Photochemistry and Photobiology A Chemistry · doi:10.1016/j.jphotochem.2022.114239 · Cited by 7 · see citing works

Classification of some chemical drugs by genetic algorithm and deep neural network hybrid method

Karakaplan, M., & Avcu, F. M. (2021) · Concurrency and Computation Practice and Experience · doi:10.1002/cpe.6242 · Cited by 6 · see citing works

A survey of solid form landscape: Trends in occurrence and distribution of various solid forms and challenges in solid form selection

Li, Z. J., Lu, Y., Wang, R., Dong, X., Chen, P., Duan, J., Shi, M., Wang, L., & Liu, Y. (2024) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2024.10.045 · Cited by 6 · see citing works

Contributions of African Medicinal Plants to Modern Drug Discovery

Babandi, A. (2025) · Interdisciplinary biotechnological advances · doi:10.1007/978-981-96-8590-5_16 · Cited by 6 · see citing works

Enantioselective polar [2σ + 2π] cycloadditions of bicyclo[1.1.0]butanes and ortho -quinone methides enabled by chiral phosphoric acid catalysis

Xu, L. B., Zhong, Q., Zhou, Y., Liu, R., Sun, X., Liu, X.-Y., Qin, Y., & Song, H. (2025) · Organic Chemistry Frontiers · doi:10.1039/d5qo01029b · Cited by 6 · see citing works

Mercury Annual survey covering the year 1973

Seyferth, D. (1974) · Journal of Organometallic Chemistry · doi:10.1016/s0022-328x(00)83711-0 · Cited by 6 · see citing works

Complex molecules: do they add value?

Selzer, P. M., ROTH, H. ‐., Ertl, P., & Schuffenhauer, A. (2005) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2005.04.001 · Cited by 75 · see citing works

Molecular complexity and fragment-based drug discovery: ten years on

Leach, A. R., & Hann, M. M. (2011) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2011.05.008 · Cited by 168 · see citing works

About Complexity and Self-Similarity of Chemical Structures in Drug Discovery

von Korff, M., & Sander, T. (2012) · Springer eBooks · doi:10.1007/978-3-642-33914-1_39 · Cited by 10 · see citing works

A path based approach to assessing molecular complexity

Proudfoot, J. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.03.008 · Cited by 21 · see citing works