Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Rev Drug Discov. 2007 Nov;6(11):881-90.

The influence of drug-like concepts on decision-making in medicinal chemistry.

Author information

  • 1AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE15 5RH, UK. paul.leeson@astrazeneca.com

Abstract

The application of guidelines linked to the concept of drug-likeness, such as the 'rule of five', has gained wide acceptance as an approach to reduce attrition in drug discovery and development. However, despite this acceptance, analysis of recent trends reveals that the physical properties of molecules that are currently being synthesized in leading drug discovery companies differ significantly from those of recently discovered oral drugs and compounds in clinical development. The consequences of the marked increase in lipophilicity--the most important drug-like physical property--include a greater likelihood of lack of selectivity and attrition in drug development. Tackling the threat of compound-related toxicological attrition needs to move to the mainstream of medicinal chemistry decision-making.

PMID:
17971784
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Write to the Help Desk