ArticleNature chemistry2014
Efficient discovery of bioactive scaffolds by activity-directed synthesis.
Article in Nature chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed, 62 citations in OpenAlex.
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- Direct-to-Biology: Streamlining the Path From Chemistry to Biology in Drug Discovery.ChemMedChem · 2026Review
- High-Throughput Synthesis and Screening of a Cyanimide Library Identifies Selective Inhibitors of ISG15-Specific Protease mUSP18.Angewandte Chemie (International ed. in English) · 2025Article
- Toward target 2035: EUbOPEN - a public-private partnership to enable & unlock biology in the open.RSC medicinal chemistry · 2025Article
- Unifying principles for the design and evaluation of natural product-inspired compound collections.Chemical science · 2025Review
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- Deciphering the intricate linkage between the gut microbiota and Alzheimer's disease: Elucidating mechanistic pathways promising therapeutic strategies.CNS neuroscience & therapeutics · 2024Review
- Modular synthesis of functional libraries by accelerated SuFEx click chemistry.Chemical science · 2024Article
- Decoding the role of gut microbiota in Alzheimer's pathogenesis and envisioning future therapeutic avenues.Frontiers in neuroscience · 2023Review
- Photochemical single-step synthesis of β-amino acid derivatives from alkenes and (hetero)arenes.Nature chemistry · 2022Article
- A direct-to-biology high-throughput chemistry approach to reactive fragment screening.Chemical science · 2021Article
- Combining generative artificial intelligence and on-chip synthesis for de novo drug design.Science advances · 2021Article
- Natural product-informed exploration of chemical space to enable bioactive molecular discovery.RSC medicinal chemistry · 2021Review
- Computational Mapping of Dirhodium(II) Catalysts.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Activity-Directed Synthesis: A Flexible Approach for Lead Generation.ChemMedChem · 2020Article
- Activity-Directed Synthesis of Inhibitors of the p53/hDM2 Protein-Protein Interaction.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- Scalable Synthesis of Esp and Rhodium(II) Carboxylates from Acetylacetone and RhClOrganic process research & development · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The structures and biological activities of natural products have often provided inspiration in drug discovery. The functional benefits of natural products to the host organism steers the evolution of their biosynthetic pathways. Here, we describe a discovery approach--which we term activity-directed synthesis--in which reactions with alternative outcomes are steered towards functional products. Arrays of catalysed reactions of α-diazo amides, whose outcome was critically dependent on the specific conditions used, were performed. The products were assayed at increasingly low concentration, with the results informing the design of a subsequent reaction array. Finally, promising reactions were scaled up and, after purification, submicromolar ligands based on two scaffolds with no previous annotated activity against the androgen receptor were discovered. The approach enables the discovery, in tandem, of both bioactive small molecules and associated synthetic routes, analogous to the evolution of biosynthetic pathways to yield natural products.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.