Sigma-Aldrich

ChemFiles

Privileged structures for lead discovery and optimization. Indoles,* Biaryls**

"Privileged structures are a class of molecules that are capable of binding to multiple receptors with high affinity. In order to be considered privileged, a substructure should represent a molecule's core element and make up a significant portion of its total mass."

www.sigma-aldrich.com/drugdiscovery

www.sigmaaldrich.com/.../al_chemfile_v4_no8.pdf*

www.sigmaaldrich.com/.../al_chemfile_v5_n2.pdf**

Prestwick's Privileged Building Blocks

The Privileged Structure Concept

"The retrospective analysis of the chemical structure of various drugs used in medicine led medicinal chemists to identify some molecular motifs that are more frequently associated with higher biological activity than other structures. Such molecular motifs were called "privileged" structures by Evans et al.*, to mean substructures that confer activity to two or more different receptors. The implication was that the privileged structure provides the scaffold, and that substitutions on the scaffold provide specificity for a particular receptor."

* J. Med. Chem. 1988, 31, 2235- 2246.

www.prestwickchemical.com/newproducts.htm

TimTec

Privileged Structure Library

"Evaluation of the chemical structures of commercially available pharmaceuticals and agents with good pharmacological activity led to identification of molecular motifs that are more frequently associated with higher biological activity than other substructures. These motifs were given the "privileged" label when they were found to be present in molecules that were active at two or more different receptors."

(benzhydryl, biphenyl, aza-biphenyl,diaza-biphenyl, dihydropyridine, anilino-pyridine, pyrimidine, or triazine, phenylpiperazine)

www.timtec.net/products/privileged_structure.htm

ChemDiv

Chemical diversity

"Privileged structure - Substructural feature which confers desirable (often drug- like) properties on compounds containing that feature. Often consists of a semi- rigid scaffold which is able to present multiple hydrophobic residues without undergoing hydrophobic collapse."

www.chemdiv.com/about/faq/p.phtml

Masterkey

"The Masterkey approach is a process that generates a privileged structure*, tailor-made for binding to the ATP binding pocket of kinases, and a substitution pattern of low molecular weight fragments around the "privileged structure" that interacts with other specificity pockets adjacent to the ATP binding site."

* rigid molecular scaffold

www.axxima.de/axxima_php/html/sub/print_masterkey.php

Array BioPharma

Optimer® Building Blocks (privileged structural motifs)

Privileged Molecules: "Recurring fragments or structural motifs are often referred to as “privileged” structures for their affinity to bind to pharmaceutically relevant targets. For example, seventy percent of all drugs from the World Drug Index (Derwent) contain the aromatic structural motif."

www.arraybiopharma.com/OptimerBuildingBlocks/...asp

Avalon pharmaceuticals

Parallel Synthesis: "Avalon is also developing proprietary chemistries to produce diverse libraries based on privileged structures."

www.avalonrx.com/science/innovation_5_2.html

Amedis

"the construction of validated scaffolds (privileged structures) incorporating silicon – “a Silicon Fast Follower NCE” – can provide an advantage over carbon analogues."

www.amedis-pharma.com/New_Web/company.htm

peakdale Molecular

"Peakdale scientists work closely with our clients to design libraries around privileged structures-"

www.peakdale.co.uk/lead_optimisation.htm