CHIMIA International Journal for Chemistry · 1997 · 32 citations · 0 references
PharmacyChemistryMedicinal ChemistryCombinatorial ChemistryDrug DiscoveryLead OptimizationCombinatorial SynthesisHit-to-lead OptimizationLead Compound DesignLead DiscoveryParallel SynthesisSolution-phase SynthesisChemical Library SynthesisCombinatorial Lead GenerationMedicinal Chemistry ApplicationsSolution-phase Combinatorial SynthesisSolution-phase Parallel Synthesis
Solution‑phase combinatorial chemistry complements solid‑phase methods, enabling lead discovery while also highlighting limitations, and its applicable chemistries are rapidly expanding. The study aims to improve the quality of array‑format compounds by describing several emerging approaches. The authors outline several new strategies for producing higher‑quality compounds in array formats. Solution‑phase parallel synthesis of discrete compounds is a popular and effective method for lead generation and optimisation.
Solution-phase approaches in combinatorial chemistry complement solid-phase approaches and each can be used to advantage in particular circumstances. Solution-phase synthesis of pools of compounds, whilst allowing successful identification of a selection of good lead structures for medicinal chemistry programmes, also reinforced a number of the disadvantages of such an approach. Solution-phase parallel synthesis of discrete compounds has, however, proved to be a very useful and popular approach both for lead generation and in lead optimisation work. The range of chemistry suitable for use in such approaches is expanding rapidly and some of these chemistries are discussed. The current focus is on enhancing the quality of compounds prepared in array formats, and we describe a number of useful approaches which are being developed to that end.