3 years ago

Privileged Structures Revisited

Privileged Structures Revisited
Petra Schneider, Gisbert Schneider
Privileged structures inspire compound library design in medicinal chemistry. We performed a comprehensive analysis of 1.4 million bioactive compounds, with the aim of assessing the prevalence of certain molecular frameworks. We used the Shannon entropy formalism to quantify the promiscuity of the most frequently observed atom scaffolds across the annotated target families. This analysis revealed an apparent inverse relationship between hydrogen-bond-acceptor count of a scaffold and its potential promiscuity. The results further suggest that chemically easily accessible scaffolds can serve as templates for the generation of bespoke compound libraries with differing degrees of multiple target engagement, and heterocyclic, sp3-rich frameworks are particularly suited for target-focused library design. The outcome of our study enables us to place some of the many narratives surrounding the concept of privileged structures into a critical context. Drug design: Analysis of 1.4 million bioactive compounds revealed an apparent inverse relationship between the sp3-atom and hydrogen-bond-acceptor count of a scaffold and its potential promiscuity in terms of binding a variety of protein targets.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201702816

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.