Combinatorial libraries, peptide-based pharmaceuticals

Spiropiperidines have the ability to orient substituents in mimicry of a peptidic [3-tum which could explain their activity against a range of peptidic GPCR targets. Ono Pharmaceuticals developed a solid phase combinatorial library based upon the Ugi reaction to generate potential lead matter for a range of chemokine receptors. From their initial 576-compound collection, several compounds showed low... 

The combinatorial decoration or derivatization of existing natural products is a popular method for library creation. Among targets for such exercises are the alkaloids yohimbine and scopolamine, terpenoids and steroids, and the heterocyclic peptide antibiotic GE-2270A (Figure 11). In the latter case, combinatorial variation was instrumental in the discovery of a developmental candidate now in clinical trials at Vicuron. Pfizer, the world s largest pharmaceutical company, recently acquired Vicuron for the sum of 1.9 billion, a mark of approval for natural product-based combinatorial chemistry. 

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