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

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