BioCores: identification of a drug/natural product-based privileged structural motif for small-molecule lead discovery

  title={BioCores: identification of a drug/natural product-based privileged structural motif for small-molecule lead discovery},
  author={Roman V. Kombarov and Andrea Altieri and Dmitry Genis and Mikhail Kirpichenok and Valeriy Kochubey and Natalia Rakitina and Zoya Titarenko},
  journal={Molecular Diversity},
The analysis of known drugs (Comprehensive Medicinal Chemistry database (2008 version): and natural products (Koch et al., Proc Natl Acad Sci USA 102:17272–17277, 2008) has led to the identification of privileged saturated and aromatic heterocyclic ring pairs that we have termed as “BioCores.” This article explains how the BioCores can be used for the design of novel lead-like scaffolds. 
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Charting biologically relevant chemical space: a structural classification of natural products (SCONP).
A structural classification of natural products (SCONP) is reported as organizing principle for charting the known chemical space explored by nature and provides a viable analysis- and hypothesis-generating tool for the design of natural product-derived compound collections. Expand
Novel chemical space exploration via natural products.
The chemical space navigation tool ChemGPS-NP is used to evaluate the chemical space occupancy by NPs and bioactive medicinal chemistry compounds from the database WOMBAT and property based similarity calculations were performed to identify NP neighbors of approved drugs. Expand
The role of natural product chemistry in drug discovery.
  • M. Butler
  • Medicine
  • Journal of natural products
  • 2004
To continue to be competitive with other drug discovery methods, natural product research needs to continually improve the speed of the screening, isolation, and structure elucidation processes, as well addressing the suitability of screens for natural product extracts and dealing with issues involved with large-scale compound supply. Expand
The properties of known drugs. 1. Molecular frameworks.
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Molecular diversity in the context of leadlikeness: compound properties that enable effective biochemical screening.
  • G. Rishton
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  • 2008
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Property Distributions: Differences between Drugs, Natural Products, and Molecules from Combinatorial Chemistry
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