Lecture 4

  1. Activity
    Particular biological or pharmacological effect
  2. Potency
    Strength of that effect (~concentration)
  3. Taxol
    • - Anticancer drug from Pacific Yew
    • - Affects mitosis by stabilizing microtubules + prevents breakdown needed for cell division.
  4. Taxol Structure and Docetaxel
    • 1) Replaceable phenyl group (n-acyl).
    • 2) Replaceable acetyl group.
    • 3) Has heterocycle.
    • 4) Has ketone group.
  5. Lead discovery 
    Privileged structures that help make the framework for creating medicine.

    Only 32 scaffolds are used in 1/2 known drugs.

    Benzodiazapine is a scaffold. 
  6. Therapeutic Index

    Bigger TI is better. Cancer drug ~ 1-5, all else 10-100
  7. LD50
    Lethal dose 50; dose that kills 50% of test animals.
  8. ED50
    Effective dose 50; dose that provides maximal therapeutic effect is in 50% test animals.
  9. Homologation
    Make series that differ by a constant unit (-CH2-)

    1. Max space-filling w/ receptor to max vander-wall interaction

    2. Modulate hydrophobicity.
  10. Isomer or "Chain Branching"
    Adding or removing branching from compounds.

    1. Changes shape, receptor matching, and surface area.

    2. Lipophilicity is beter when it is straight change bc it fits into membrane better.
  11. Ring-chain transformation
    Keep # of atoms constant, or but can strain, release constraints

    • 1. Moderate greasiness
    • 2. Pre-organize cmf (good or bad)
    • 3. Open up new synthetic routes
    • 4. Alter metabolism
  12. Bioisosters
    Group that have similar chemical or physical properties which broadly produce similar biological effects.

    • Replacement may alter:
    • - receptor interaction.
    • - ADME.
    • - Toxicity.
  13. Classical bioisoster
    Generally have same shape but replace certain atoms with univalent or divalent molecules to alter ADME/etc.
Card Set
Lecture 4
SAR, TI, LD50, ED50, Modification tyes