Introduction

The advent of combinatorial chemistry has left a profound impact on chemistry in general, and on drug design in particular. The wealth of data obtained in combinatorial chemistry experiments has asked for the development of computer methods to process this large amount of information.

Until now, however, nearly all computer-based methods have only taken the structure of compounds into account to address such problems as diversity of chemical libraries, the design of focused or drug-like libraries, and the analysis of results from high-throughput screening.

Much less attention has been devoted to the development of computer methods for planning and analyzing the chemical reactions employed in combinatorial chemistry experiments. However, in recent years it has become increasingly clear that an efficient exercise of combinatorial chemistry needs to pay much attention to an understanding of chemical reactions employed in an experiment.

Three major questions have to be answered that need information on chemical reactions:

• How can I plan the synthesis of my library?

• Which products will I get in a given reaction?

• What can I learn from a series of reactions that I have performed?

The large amount of information gained in combinatorial chemistry experiments quite clearly suggests the use of computerized methods for ordering and analyzing this information.

In fact, we believe that combinatorial chemistry in general, and parallel synthesis in particular, provides information that can greatly foster our understanding of chemical reactions. A series of structural variations of a certain reaction type performed under identical conditions, or a given reaction performed under systematic variations of reaction conditions provide information that can give us unique insights into the scope and limitations of a reaction or reaction type.

The variety of questions that have to be answered when performing combinatorial chemistry have made us develop three different program systems, each one specifically focused to answer one of the questions posed above. The three systems are:

• WODCA for designing the synthesis of combinatorial libraries

• EROS for modeling chemical reactions to predict chemical reactivity and the outcome of a chemical reaction

• CORA for analyzing a series of reaction instances.

In the following, we will briefly outline these systems and some of the methods incorporated within them and then show some applications.

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