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Molecular Diversity

, Volume 16, Issue 3, pp 477–487 | Cite as

Focused enumeration and assessing the structural diversity of scaffold libraries: conformationally restricted bicyclic secondary diamines

  • Oleksandr O. Grygorenko
  • Roman Prytulyak
  • Dmitriy M. Volochnyuk
  • Volodymyr Kudrya
  • Oleksiy V. Khavryuchenko
  • Igor V. Komarov
Full-Length Paper

Abstract

Comprehensive enumeration of conformationally restricted bicyclic secondary diamines (CRDA) was performed within defined structural limits, yielding a library of all theoretically possible compounds of this class, potentially useful as building blocks for drug design. In order to assess structural diversity of the generated library, molecular geometries of the library members were optimized using DFT calculations. It was shown that the distance between the amino groups and their relative orientation in space vary widely over the whole library, which might be beneficial for diversity-oriented conformational restriction approach in drug discovery. There are many representatives of “three-dimensional” scaffolds in the CRDA library. Selected literature data on biological activity of the known CRDA derivatives were discussed, demonstrating utility of the CRDA scaffold hopping in drug design.

Keywords

Drug design Chemical space Scaffold hopping Bicyclic diamines Molecular rigidity Three-dimensional scaffolds Diversity-oriented conformational restriction 

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Oleksandr O. Grygorenko
    • 1
    • 2
  • Roman Prytulyak
    • 1
  • Dmitriy M. Volochnyuk
    • 2
    • 3
  • Volodymyr Kudrya
    • 3
  • Oleksiy V. Khavryuchenko
    • 1
  • Igor V. Komarov
    • 1
    • 2
  1. 1.Kyiv National Taras Shevchenko UniversityKyivUkraine
  2. 2.Enamine Ltd.KyivUkraine
  3. 3.Institute of Organic Chemistry National Academy of Sciencesof UkraineKyivUkraine

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