Tiêu đề 3. COMBINATORIAL CHEMISTRY.pdf ✅

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
PHARMD GURU Page 3 COMBINATORIAL CHEMISTRY WITHIN DRUG DESIGN:  Combinatorial chemistry can impact at lead discovery.  Traditionally lead drugs were found from:  Natural products.  Synthetic custom crafted organic molecules made in small numbers.  Analogues of known actives (analogue me-toos).  High throughput screening (HTS) requires large numbers of compounds to fuel the discovery process.  As an alternative to traditional synthesis many compounds rapidly constructed was needed. TECHNIQUES USED IN THE COMBINATORIAL SYNTHESIS: THERAPEUTIC TARGET LEAD DISCOVERY LEAD OPTIMISATION DEVELOPMENT CANDIDATE DRUG COMBINATORIAL CHEMISTRY CAN IMPACT HERE. SOLID PHASE TECHNIQUE Solid Support Method. Parallel Synthesis. Mixed Combinatorial Synthesis. Mixed & split combinatorial Synthesis. SOLUTION PHASE TECHNIQUE