Med Chem Test #2: QSAR

QSAR

QSAR stands for

Quantitative Structure Activity Relationships

What is a QSAR?

correlates measurable or calculated physical or molecular properties to some specific biological activity in terms of an equation

Why is QSAR needed?

to predict the biological activity of a drug candidate before biological testing. Cost efficient

QSAR equation example

Hansch: log(1/C) = k1logP - k2(logP)² + k3(sigma) + k4

Hansch equatx (log(1/C) = k1logP - k2(logP)² + k3(sigma) + k4): meaning of C

min effective dose

Hansch equatx (log(1/C) = k1logP - k2(logP)² + k3(sigma) + k4): meaning of P

octanol - h20 partition coefficient

Hansch equatx (log(1/C) = k1logP - k2(logP)² + k3(sigma) + k4): meaning of sigma

Hammett substituent constant

6 measurable physical properties

density, pKa, boiling point, molecular weight, dipole moment, refractive index

6 calculated physical properties

HOMO, LUMO energy, polarizability, molecular volume, vdW surface area, Taft’s steric parameter

3 most common parameters names

partition coefficient, hammett constant, taft’s steric parameters

P is _ and measures:

partition coefficient, hydrophobicity/lipophilicity

(sigma) is _ and measures:

Hammett constant, electronic effects

(Es) is _ and meausures:

Taft’s steric parameters, steric effects

positive sigma (EW or ED)

EW

negative sigma (EW or ED)

ED

min ration of data set (compounds) to descriptors (parameters being modified)

5:1

Why is 5:1 raio required

Too few compounds will give you a falsely high correlation

how many points determine a line

2

how many points determine a plane

3

How many descriptors are typically included in a final QSAR equation?

3-5