Lecture 4

Particular biological or pharmacological effect

Strength of that effect (~concentration)

• - Anticancer drug from Pacific Yew
• - Affects mitosis by stabilizing microtubules + prevents breakdown needed for cell division.

• 1) Replaceable phenyl group (n-acyl).
• 2) Replaceable acetyl group.
• 3) Has heterocycle.
• 4) Has ketone group.

Privileged structures that help make the framework for creating medicine.

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

Benzodiazapine is a scaffold. 

LD50/ED50

Bigger TI is better. Cancer drug ~ 1-5, all else 10-100

Lethal dose 50; dose that kills 50% of test animals.

Effective dose 50; dose that provides maximal therapeutic effect is in 50% test animals.

Make series that differ by a constant unit (-CH2-)

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

2. Modulate hydrophobicity.

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.

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

Group that have similar chemical or physical properties which broadly produce similar biological effects.

• Replacement may alter:
• - receptor interaction.
• - ADME.
• - Toxicity.

Generally have same shape but replace certain atoms with univalent or divalent molecules to alter ADME/etc.