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Related Experiment Videos

The use of bioisosteric groups in lead optimization.

P H Olesen1

  • 1Novo Nordisk A/S, Novo Nordisk Park, 2760 Maaloev, Denmark. phol@novonordisk.com

Current Opinion in Drug Discovery & Development
|December 1, 2001
PubMed
Summary

Bioisosteric replacement is a valuable strategy for optimizing drug leads. This technique refines compounds for clinical trials by enhancing target selectivity and improving pharmacokinetic properties.

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Area of Science:

  • Medicinal Chemistry
  • Drug Discovery
  • Pharmacology

Background:

  • Bioisosterism, the concept of similar biological activity in structurally related compounds, was introduced by Friedman fifty years ago.
  • The principle of bioisosterism has been widely applied in drug discovery for lead compound optimization.
  • Recent advances in recombinant protein expression and high-throughput screening have expanded the pool of potential drug targets.

Purpose of the Study:

  • To highlight the significant value of bioisosteric replacement in fine-tuning lead compounds for clinical development.
  • To emphasize the utility of bioisosterism in improving drug selectivity and pharmacokinetic profiles.
  • To illustrate the application of bioisosteres in lead optimization with recent literature examples.

Main Methods:

  • Literature review of recent examples showcasing bioisosteric replacement in drug discovery.
  • Analysis of the role of bioisosterism in optimizing lead compound properties.
  • Focus on applications in enhancing target selectivity and pharmacokinetic parameters.

Main Results:

  • Bioisosteric replacement is a powerful tool for optimizing lead compounds, particularly for clinical suitability.
  • The strategy effectively improves selectivity for specific biological targets.
  • Pharmacokinetic properties of lead compounds can be significantly enhanced through bioisosteric modifications.

Conclusions:

  • Bioisosteric replacement remains a crucial and effective strategy in modern drug discovery and development.
  • Its application is vital for refining drug candidates to meet the rigorous demands of clinical trials.
  • The judicious use of bioisosteres contributes to the successful optimization of drug properties, including selectivity and pharmacokinetics.

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