Heterocyclic reactive intermediates for drug discovery

During the past 25 years almost every part of the drug discovery process has undergone radical change For instance using robotics and combinatorial techniques chemists can now synthesise single libraries that contain more compounds than existed in the total chemical literature of 1980.

One of the few things that has not changed is that the majority of medicines are still small synthetic organic molecules and that a high proportion of them contain a heterocyclic ring.

As technological advances overcome the traditional rate limiting steps in the drug discovery pathway so new factors become the choke points.

Thus the actual synthesis of a focussed library of say 500 compounds has become a trivial exercise provided that the necessary building blocks are available. However if the building blocks are not available and have to be synthesised then the construction of even a small library may become far from trivial.

Maybridge Ltd therefore resolved to produce a comprehensive collection of these molecules specifically designed to help the drug discovery process. Such a collection needs to provide chemical as well as structural diversity. For medicinal chemists both the pharmacophoric and pharmacokinetic profiles of a molecule are important.

The most important parameters are aqueous solubility, lipophilicity, molecular weight and hydrogen bond donor and acceptor capabilities. The preferred values for the latter four properties as determined by an analysis of The World Drug Index form the basis of Lipinski's arule of five'1.

Library design frequently involves in-silico diversity analysis so it is essential that all the building blocks are available since the non-availability of just one intermediate necessitates starting the analysis again from scratch.

In order to ensure continuous off the shelf 100percent availability the compounds are prepacked under argon in 250mg and 1g amounts.

Maybridge Ltd is based in Geel, Belgium. www.maybridge.com

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