Drug Design Strategies Flashcards Preview

Med Chem > Drug Design Strategies > Flashcards

Flashcards in Drug Design Strategies Deck (20):
1

Xenobiotic definition

Xeno=foreign
Biotic=substance

2

Dissociation constant (Kd)

Concentration of drug that gives 50% receptor occupancy
Equal to 1/Keq

3

Small Kd values indicate...

A tight-binding drug-receptor interaction

4

Agonist

Binds to receptor and mimics the effect of the endogenous ligand (natural substance)

5

Antagonist

Binds to receptor but gives no biological effect (blocks binding of agonists to the receptor)

6

Partial agonist

An agonist that doesn't give maximal effect at saturation

7

Inverse agonist

Binds to receptor and gives an effect which is opposite to an agonist (rare)

8

Solubility of drugs

Drugs need to be partially water soluble (living cells are an aqueous environment) as well as partially fat soluble (living cells are surrounded by lipid bilayers)

9

Partition coefficient between water and n-octanol

Most common measure of hydrophobicity
log P= log (drug in octanol/drug in water)
log P=0, then drug is equally soluble in water and octanol

10

Prodrugs

Compounds that are inactive in their native form but are easily metabolized to the active agent
Allow for usage of drug at proper time

11

First-pass effect

Oral drugs are transported to the liver
Injectable drugs bypass this

12

Therapeutic window

Window between drug effectiveness and bad effects
Want about 3 log folds

13

Bronsted-Lowry acid vs. Bronsted-Lowry base

Acid: Proton donor
Base: Proton acceptor

14

Quantitative structure-activity relationship (QSAR)

Predicting the degree that a molecule will exhibit physiological effects

15

QSAR models

Plotting physiological response vs. a molecular trait (partition coefficient, etc.)
Type of model that fits data sometimes indicates the mechanistic details of the physiological response

16

Comparative molecular field analysis (CoMFA)

3-D QSAR
Aligning structures of drugs and comparing their effects: understanding what portions of drugs do

17

Conformational analysis

Method used to understand compound's bioactive conformation
# of conformers = (360/angle increment)^# of rotatable bonds

18

Isosteres

Different functional groups that may be interchangeable
Similar steric, electronic, and solubility characteristics

19

Lipinski rule of 5

Candidate molecule is more likely to have poor absorption or permeability if:
1. Molecular weight exceeds 500
2. Calculated log P exceeds 5
3. More than 5 H-bond donors
4. More than 10 H-bond acceptors
Doesn't apply to majority of natural products

20

High-thoroughput screening

Looking for specific functions of drugs using both computational and in vitro methods