Combinatorial Chemistry

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Combinatorial Chemistry
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What is Combinatorial Chemistry?
A synthetic strategy which leads to a large
set of compounds.
Synthesis of many structures (diversity)
Product of matrix chemistry (systematic
synthesis)
combinatorial technology, combinatorial
library molecular diversity
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Why do we need Combinatorial Chemistry ?
1. From New Drug discovery ---
biodiversity
drug design
2. From Genome Project --- post-Genome Era
more new
drug targets
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Drug Development of 21st Century
Issues ! Human Diversity ----- Customized
Drug ! Possible Targets -----
Too many
3. Combinatorial Chemistry
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possible combination of drug like compounds
1063 -64 synthesizable number of compounds
10 24 Practical number of compounds in a
library 106 with design
lt 103 with
virtual screening , virtual library
How Many We Want from Combinatorial Chemistry
Drug-like Compounds
Solution (?) -- Combination of Design
Informatics
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Paradigm Shift of Drug Development

• 70 Natural Products 80 Rational
  Design
• 90 Combi. Chem. HTS
• 00 Information Guided Design

Rational Design
Serendipity
100
1013 ( immune system)
Diverse Design
106
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Combinatorial Chemistry
1. Nature does it all the time. -- can we mimic
mother nature ?
-- Immune System Molecular Diversity
2. Are there ways to automate the synthesis ?
-- Peptide synthesizer 40 min./cycle -- DNA
synthesizer 1.5 min./cycle
3. Are there ways to generate many compounds at a
time ?
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Combinatorial Chemistry
-- Peptide synthesizer 40 min./cycle -- DNA
synthesizer 1.5 min./cycle
Solid Phase Organic Synthesis
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Combinatorial Chemistry Strategy

• 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 mixture

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SELEX(Systematic Evolution of Ligands by
Exponential Enrichment)
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Combinatorial Chemistry Strategy
2. Matrix Library a. Pin Technology b.
Chip Technology c. Parallel Array synthesis
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Multicomponent Reaction
1. Passerini reaction
2. Ugi reaction
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Multicomponent Reaction
3. Hantzsch reaction