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.
Subject(s)
Receptors, Immunologic/antagonists & inhibitors , Receptors, Prostaglandin/antagonists & inhibitors , Small Molecule Libraries/chemistry , Carboxylic Acids/chemistry , Humans , Ligands , Protein Binding , Receptors, Immunologic/metabolism , Receptors, Prostaglandin/metabolism , Small Molecule Libraries/pharmacology , Th2 Cells/drug effects , Th2 Cells/immunologyABSTRACT
A series of C-H functionalisation plate-based chemical screens and other C-H activation protocols were developed for the chemical diversification of drug molecules. In this Letter, metalloporphyrin and other catalytic oxidation systems are described in addition to chlorination. Mifepristone and antalarmin are used as substrates. The products obtained and the biological data demonstrate the potential utility of this approach.
