What is solid phase synthesis
Synthesis of molecules using insoluble inert polymer beads where the starting compound is attached and the reaction occurs on the bead’s surface. This method allows easy purification by washing away unreacted reagents before cleaving the final product
What’s split synthesis
Method used to create large libraries of different compounds by repeatedly splitting beads into portions, then reacting each with a different reagent and mixing agai- creating numerous different compounds
Cons of split synthesis
- time consuming deconvolution process, chemical history of the compounds synthesised is lost, can be difficult to identify the active compound
What’s solution phase synthesis
Mixture of compounds in 1 pool, unlike solid phase synthesis, purification after each step requires separation techniques e.g. filtration or chromatography- making it slower and less convenient
Why is structural diversity of compounds important in combinatorial synthesis
You will be more likely to get a “hit” as if a molecule fails to become a hit and all the others are structurally similar - then they will all fail and you’ll get zero “hits”
(More compounds ≠more hits) large library of structurally diverse compounds is the ideal!!!!!!
Give an example of a drug synthesised using combinatorial methods
Torisel from rapamycin, rapamycin is a natural immunosuppressant, structurally they were able to identify the target region of rapamycin that they wanted to alter, and thus created torisel from rapamycin
What are the major disadvantages of combinatorial synthesis
Limited structural diversity of synthetic library (this can be useful when we know what region of a compound we want to target and so creating structurally similar compounds wouldn’t be a bad thing here e.g. with torisel), wastage of raw material, wastage of assay material,
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1) Overview Of Drug Discovery12
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2) Drug Targets13
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3) Combinatorial Methods7
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4) Different Approaches Of Drug Discovery10
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5) Hit To Lead Activities32
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6) Computational Chemistry13
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7) High Input Screening24
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8) Patents3
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9) Pharmacogenomics & Pharmacogenetics11
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10) Active Compounds & Ethnopharmacology12
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11) Aseptic Prep & GMP17
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12) Toxicology In Lead Selection17
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13) Quality By Design3
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14) Population PK Modelling9
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15) Protein Delivery20
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16) Animal Testing6
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17) Clinical Trials (protocols, Design,…)8
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18) Drug Licensing8
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19) Toxicology And Preclinical Testing10
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20) Case Study In Biologics Development12
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21) Case Study : Malaria12
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22) Investigational New Drug Application19
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23) Toxicology & Preclinical Testing 220
