10. Reaction-Driven De Novo Design: a Keystone for Automated Design of Target Family-Oriented Libraries

  1. Gisbert Schneider
  1. Markus Hartenfeller,
  2. Steffen Renner and
  3. Edgar Jacoby

Published Online: 11 OCT 2013

DOI: 10.1002/9783527677016.ch10

De novo Molecular Design

De novo Molecular Design

How to Cite

Hartenfeller, M., Renner, S. and Jacoby, E. (2013) Reaction-Driven De Novo Design: a Keystone for Automated Design of Target Family-Oriented Libraries, in De novo Molecular Design (ed G. Schneider), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany. doi: 10.1002/9783527677016.ch10

Editor Information

  1. ETH Zürich, Institute of Pharmaceutical Sciences, Wolfgang-Pauli-Strasse 10, 8093 Zürich, Switzerland

Author Information

  1. Novartis Pharma AG, Forum 1, Novartis Institutes for BioMedical Research, Novartis Campus, CH-4056 Basel, Switzerland

Publication History

  1. Published Online: 11 OCT 2013
  2. Published Print: 13 NOV 2013

ISBN Information

Print ISBN: 9783527334612

Online ISBN: 9783527677016



  • structure–activity relationship;
  • de novo design;
  • family-focused libraries;
  • reaction-driven approach;
  • GPCRs;
  • ELNs


Many de novo design programs focus primarily on the design of novel compounds to modulate a single biological target. While this is obviously the primary objective, promising candidate compounds need to fulfill a wide range of additional requirements in order to be of real value, for example, water solubility or the ability to cross cellular membranes. Of particular relevance in praxis is also the ease of access by chemical synthesis for both the designed candidate compounds themselves and close structural analogs for fast determination of structure–activity relationship (SAR). Such series of congeneric compounds can be of additional merit to probe structurally related target proteins. Combinatorial chemical libraries represent a common time- and resource-efficient tool in medicinal chemistry to access such compound series. A fusion of the two concepts of automated de novo design and combinatorial compound libraries can therefore provide a powerful tool for lead discovery. Reaction-based strategies for in silico compound generation represent a key technology enabling this amalgamation.