Biological chemistry lead compounds

D. J. Lythgoe (Rhdne-Poulenc Rorer, UK) and C. A. Ramsden (Keele University) cover the chemistry of 4- and 5-aminoimidazoles, compounds of recently recognized biological importance leading to significant interest in their investigation. 

Jacoby E, Schuffenhauer A, Addin P. (2004) The contribution of molecular informatics to chemogenomics. Knowledge-based discovery of biological targets and chemical lead compounds. In H Kubini, G Muller (eds), Chemogenomics in Drug Discovery — A Medicinal Chemistry Perspective, pp. 139-166. Wiley-VCH,Weinheim. 

Computer modelling has reduced the need to synthesize every analogue of a lead compound. It is also often used retrospectively to confirm the information derived from other sources. Combinatorial chemistry, which originated in the field of peptide chemistry, has now been expanded to cover other areas. The term covers a group of related techniques for the simultaneous production of large numbers of compounds for biological testing. Consequently, it is used for structure action studies and to discover new lead compounds. The procedures may be automated. 

A more random approach to discovering a lead is the combinatorial chemistry approach (see Chapter 6). This uses a simultaneous multiple synthesis technique to produce large numbers of potential leads. These potential leads are subjected to rapid high throughput biological screening to identify the most active lead compounds. Once identified, these lead compounds are subject to further development. 

The book explores the invention of new chemical reactions for use in the synthesis of biologically and economically important compounds. It begins with a mechanistic study of the industrial importance of the pyrolysis of chlorinated alkanes. It continues with a theory on the biosynthesis of phenolate derived alkaloids involving phenolate radical coupling. Included in the book is a description of the work on nitrite photolysis (the Barton Reaction) which involved the invention of new radical chemistry leading to a simple synthesis of the hormone, aldosterone. In two final chapters Dr Shyamal Parekh views Professor Barton s pioneering work from the modern perspective, with a review of recent applications in industry and research. 

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