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Combinatorial Chemistry. Synthesis of many structures (diversity) combinatorial technology, combinatorial library molecular diversity What is Combinatorial

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  • Combinatorial Chemistry

  • Synthesis of many structures (diversity) combinatorial technology, combinatorial library molecular diversityWhat is Combinatorial Chemistry? A synthetic strategy which leads to a large set of compounds. Product of matrix chemistry (systematic synthesis)

  • Why do we need Combinatorial Chemistry ?1. From New Drug discovery --- biodiversity drug design2. From Genome Project --- post-Genome Era more new drug targets

  • Issues : ! Human Diversity ----- Customized Drug ! Possible Targets ----- Too many3. Combinatorial ChemistryDrug Development of 21st Century

  • Drug-like CompoundsHow Many We Want from Combinatorial Chemistry possible combination of drug like compounds : ~ 1063 -64

    synthesizable number of compounds : ~ 10 24

    Practical number of compounds in a library : 106 with design < 103 with virtual screening , virtual librarySolution (?) -- Combination of Design & Informatics

  • 70 : Natural Products 80 : Rational Design90 : Combi. Chem.& HTS 00 : Information Guided DesignRational DesignDiverse DesignSerendipity1001061013( immune system)Paradigm Shift of Drug Development

  • 1. Nature does it all the time. -- can we mimic mother nature ?2. Are there ways to automate the synthesis ?-- Immune System Molecular Diversity-- Peptide synthesizer : 40 min./cycle-- DNA synthesizer : 1.5 min./cycle3. Are there ways to generate many compounds at a time ?Combinatorial Chemistry

  • Combinatorial Chemistry-- Peptide synthesizer : 40 min./cycle-- DNA synthesizer : 1.5 min./cycleSolid Phase Organic Synthesis

  • Mixture Library

    a. SELEX -- nucleotide library --- 4n

    b. Positional scanning -- peptide library --- 20n

    c. Phage Display -- peptide library --- 108

    d. Split- mix method ( bead tech.) -- general

    e. simple mixtureCombinatorial Chemistry : Strategy

  • SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

  • 2. Matrix Library

    a. Pin Technology

    b. Chip Technology

    c. Parallel Array synthesisCombinatorial Chemistry : Strategy

  • Multicomponent Reaction1. Passerini reaction2. Ugi reaction

  • Multicomponent Reaction3. Hantzsch reaction

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