Use of libraries to access new chemical space: applications to CRTH2

M Abid Masood; Mark Gardner; Kevin Dack; David Winpenny; Graham Lunn

doi:10.1016/j.bmcl.2012.04.041

Use of libraries to access new chemical space: applications to CRTH2

Bioorg Med Chem Lett. 2012 Jun 1;22(11):3682-7. doi: 10.1016/j.bmcl.2012.04.041. Epub 2012 Apr 20.

Authors

M Abid Masood¹, Mark Gardner, Kevin Dack, David Winpenny, Graham Lunn

Affiliation

¹ Pfizer Worldwide Medicinal Chemistry, Sandwich Laboratories, Sandwich, UK. mabidmasood@gmail.com

PMID: 22560471
DOI: 10.1016/j.bmcl.2012.04.041

Abstract

The generation of novel CRTH2 ligands in heavily congested chemical space, by de novo design of libraries is disclosed. Novel (1719) compounds across seven libraries were synthesised. More than 100 of these compounds showed binding potency <3 μM against CRTH2, with the most potent being 247 nM. These libraries produced novel series and demonstrated that this approach is a viable one.

MeSH terms

Carboxylic Acids / chemistry
Humans
Ligands
Protein Binding
Receptors, Immunologic / antagonists & inhibitors*
Receptors, Immunologic / metabolism
Receptors, Prostaglandin / antagonists & inhibitors*
Receptors, Prostaglandin / metabolism
Small Molecule Libraries / chemistry*
Small Molecule Libraries / pharmacology
Th2 Cells / drug effects
Th2 Cells / immunology

Substances

Carboxylic Acids
Ligands
Receptors, Immunologic
Receptors, Prostaglandin
Small Molecule Libraries
prostaglandin D2 receptor