This document discusses combinatorial chemistry and high-throughput screening methods. It provides an introduction to combinatorial chemistry, explaining that it allows for rapid synthesis of large numbers of structurally similar molecules. High-throughput screening is then discussed as a process for efficiently testing large libraries of potential drug compounds. Some key advantages of combinatorial chemistry are rapid synthesis, ability to produce large numbers of compounds, and increased likelihood of success in drug discovery. Potential challenges are difficulty in characterizing unexpected products and substrate selection. Current applications discussed include drug development areas like histamine receptor antagonists and dihydrofolate reductase inhibitors.

1. Combinatorial chemistry and high through put
screening method
PRESENTED BY: Aarti R. KAMBLE
m pharm department of pharmacology
S. R. T. M UNIVERSITY NANDED

2. CONTENT
INTRODUCTION
CONCEPT OF COMBINATORIAL CHEMISTRY
HIGH THROUGHPUT SCREENING
KEY SUCCESS FACTORS FOR MODERN LEAD DOSCOVERY

3. ADVANTAGE AND DISADVANTAGE
CURRENT SCENARIO OF COMPANIES USING COMBINATORIAL
DRUG DESIGN
A STRATEGY FOR FUTURE
APPLICATION

4. COMBINATORIAL CHEMISTRY
INTRODUCTION:
In 1960 combinatorial chemistry was introduced.
In 1963, combinatorial synthesis of peptide on resin beds was done by Bruce
merrified.
New method developed by academics and research to decrease to the time and
cost of producing effective marketable competitive new drugs.
Scientist use combinatorial chemistry to create large number molecule that can be
detected efficiently.

5. Definition
Is a technique by which large numbers of different but structurally similarly
molecules are produced rapidly and submitted for pharmacological assay.
The techniques uses the same reaction condition with the same reaction vessels to
produce a large of range of analogues.

6. Principle of combinatorial chemistry
Is to prepare very large number of compound then identify more component from
these compound
 This technique by which distinct molecule which is structurally large may
synthesized in a short time and submit by pharmacological study

7. Concept of combinatorial chemistry
Important in material science and drug discovery
Basic idea abut this study
Formation of numbers of compound in one time
Convention reaction: A + B A – B
Combinatorial chemistry: A(1-n) + B(1-n) A(1-n) – B(1-n)
High throughput-screening which gives effective substance

8. Design of combinatorial chemistry
A sequential attachment of building blocks.
The non sequential attachment of building blocks using B as template

9. Combinatorial synthesis
Solution phase synthesisSolid phase synthesis
Parallel
synthesis
Mix and
split
technique
Tea bag
synthesis
Multi-pin
synthesis
Laminar
solid
phase
Microchi
p special
array

10. High throughput screening
Is the process of assaying a large number of potential efforts of biological activity
against target
HTS applied to the screening of combinatorial chemistry, genomics, protein, and
peptide libraries
Reducing the cost and improving screening throughput and reduced manipulation
steps

11. Goal of HTS
To accelerate drug discovery by screening large libraries often composed of
hundreds of thousand of compound at rate exceed 20000 compound per weak.
This technique focus on:
 Various assay adaptation
 Robotic equipment
 Implementation strategies

12. Key success factors for modern lead discovery
HTS
TIME
COSTSQUALITY

13. Advantage of combinatorial chemistry
Rapid synthesis
Large number
Richer data from screening
Increased likelihood success
Broader patent protection

14. Disadvantage
Difficulty to characterise the identification of unexpected or un wonted product
combination there is difficulty to analyse will cause the problem.
Substrate molecule is measure problem.
In solid phase reaction steps carefully planned.

15. Current scenario of companies using
combinatorial drug design
Increased demand for new drug
Solution phase synthesis
The most efficient optimization of lead structures is performed by application of
intelligent selection with filter function
A HTOS process has been design to transfer crude reaction mixture to purified
compound of known identity weight

16. A strategy for the future
The globalization of drug market
Advance over traditional scientific research methodology
For mass of information
The seminal human genome project is also expanding use of combinatorial
chemistry
New technique-Dynamic combinatorial chemistry has been introduced

17. APPLICATION
Lead Optimization of Histamine H3 Receptor Antagonism.
Lead Optimisation of Dihydrofolate Reductase Inhibitors
Synthesis of Peptide
AN Efficient Method for Making Azido Solid Support
High Throughput Screening

18. References
http//en.Wikipedia.org/wiki/drug discovery
http//drug discovery.weebly.com
www.slide share net/…/combinatorial-chemistry-hts-and-its-application
A Review on combinatorial chemistry , S. M. Shailkh published date
19/4/2017,volume-1.