Tiêu đề 3. COMBINATORIAL CHEMISTRY.pdf ✅

PHARMD GURU Page 1 INTRODUCTION:  Combinatorial chemistry is a technique by which large numbers of different but structurally similar molecules are produced rapidly and submitted for pharmacological assay.  This technique uses the same reaction conditions with the same reaction vessels to produce a large range of analogues.  Technique invented in the late 1980s and early 1990s to enable tasks to be applied to many molecules simultaneously. ROLE OF COMBINATORIAL CHEMISTRY - DRUG DISCOVERY PROCESS:  Applications of combinatorial chemistry are very wide Scientists use combinatorial chemistry to create large populations of molecules that can be screened efficiently.  By producing larger, more diverse compound libraries, companies increase the probability that they will find novel compounds of significant therapeutic and commercial value.  Provides a stimulus for robot-controlled and immobilization strategies that allow high-throughput and multiple parallel approaches to drug discovery. ADVANTAGES:  Fast: Combinatorial approach can give rise to million of compound in same time as it will take to produce one compound by traditional method of synthesis.  Economical: A negative result of mixture saves the effort of synthesis, purification & identification of each compound.  Easy: Isolation purification & identification of active molecule from combinatorial library is relatively easy.  Drug Discovery: Mixed Combinatorial synthesis produces chemical pool. Probability of finding a molecule in a random screening process is proportional to the number of molecules subjected to the screening process.  Drug Optimization: Parallel synthesis produces analogues with slight differences which is required for lead optimization. COMBINATORIAL CHEMISTRY
PHARMD GURU Page 2 DISADVANTAGES:  Efficiency is highly affected by compound’s size, solubility and function group.  Compounds produced tend to be Achiral of Racemic. DIFFERENCE BETWEEN CONVENTIONAL AND COMBINATORIAL SYNTHESIS:  One molecule at a time  Make - Purity - Test  Hundreds of molecule a month  Slower lead generation  High risk of failure  Many molecules at a time  Make - Test- Purity  Thousands of molecules a month  Faster leads generation  Low risk of failure DIFFERENCE BETWEEN TRADITIONAL SYNTHESIS & COMBINATORIAL SYNTHESIS: PARAMETERS TRADITIONAL SYNTHESIS COMBINATORIAL SYNTHESIS Reaction Not so simple Many a times simpler Extreme condition i.e. at extreme temperature (or) pressure May possible to use Avoid Use of highly caustic reagent Possible to use Generally avoid Use of inert atmosphere May use Avoid Multistep reaction Possible Avoid Yield of compound Gives single compound Gives chemical library STRATEGIES CONVENTIONAL COMBINATORIAL