Medicinal Chemistry, Qsar

1. QSAR PARAMETERS
Dept. of Medicinal Chemistry,
SREE DATTHA INSTITUTE OF PHARMACY,
Sheriguda, Ibrahimpatnam, Hyderabad, 501510.
Presented by:
Ashish dalpati (16U21R0051)
Under the guidance of:
Ms. G. Nikitha (M. pharm)
SREE DATTHA INSTITUTE OF PHARMACY 1

2. CONTENTS:
INTRODUCTION
QSAR PARAMETERS
LIPOPHILIC PARAMETERS
ELECTRONIC PARAMETERS
STERIC PARAMETERS
SREE DATTHA INSTITUTE OF PHARMACY 2

3. INTRODUCTION
• QSAR(Quantitative Structure Activity Relationship), proposed by “Corwen
Hansch” is a mathematical relationship between a biological activity of a
molecular system and its geometric and chemical characteristics.
• QSAR attempts to find consistent relationship between biological activity and
molecular properties, so that these rules can be used to evaluate the activity of
new compounds.
• QSAR involves the derivation of mathematical formula which relates the biological
activities of agroup of compounds to their measurable physicochemical parameters. These
parameters have major influence on the drug’s activity. QSAR derived equation take the
generalform:
• Biologicalactivity =function(parameters)
• Activity isexpressedaslog(1/c).Cisthe minimum concentration required to causea
defined biologicalresponse SREE DATTHA INSTITUTE OF PHARMACY 3

4. QSAR PARAMETERS
Various parameters used in QSAR studies are:
Lipophilic Parameters: partition coefficient,
molar refractivity
Electronic Parameters: Hammet constant
Steric Parameters: Taft’s constant, verloop
steric parameter
SREE DATTHA INSTITUTE OF PHARMACY 4

5. LIPOPHILIC PARAMETERS
• Lipophilic character of a drug is
crucial to know how easily it
crosses the cell membrane and is
also important in drug-receptor
interactions.
• Lipophilicity of a drug is measured
experimentally by testing the drugs
relative distribution which is
known as partition coefficient.
1. Partition coefficient:
• Partition coefficient P usually
expressed as logP.
• It is defined as p=
𝑥 𝑜𝑐𝑡𝑎𝑛𝑜𝑙
𝑥 𝑎𝑞𝑢𝑒𝑜𝑢𝑠
• P is a measure of the relative
affinity of a molecule for the lipid
and aqueous phase in the absence
of ionization.
• 1-Octanol is a most frequently used
lipid phase in pharmaceutical
research.
• LogP for a molecule can be
calculated from a sum of
fragmental or atom based terms
plus various corrections.
• LogP = Σ fragments + Σ corrections
SREE DATTHA INSTITUTE OF PHARMACY 5

6. Relationship between LogP and Log1/C
SREE DATTHA INSTITUTE OF PHARMACY 6

7. 2. Molar Refractivity:
• Molar refractivity is a term which determines the size and
polarizability of molecules as it is closely related with molar
properties and refractive index of particular substance which is being
tested.
• Molar refractivity is a measure of molar volume corrected by
refractive index independent of physical factors and is useful in
differentiating the structurally different compounds.
SREE DATTHA INSTITUTE OF PHARMACY 7

8. ELECTRONIC PARAMETERS
• The electronic effect of various substituent will clearly have an effect
on drug ionization and polarity.
• Have an effect on how easily drug can pass through the cell
membrane or how strongly it can interact with a binding site.
SREE DATTHA INSTITUTE OF PHARMACY 8

9. The Hammett Constant (σ):
• σ= log (Kx/Ko)
• σ=Hammet constant
• Kx=benzoic acid substituted by the group x
• Ko=dissociation constant of benzoic acid
• Hammett constant takes into account both resonance and inductive
effects; thus, the σ value depends on para or meta position of the
substituent.
• -ortho substituents are not measured due to steric effects.
SREE DATTHA INSTITUTE OF PHARMACY 9

10. SREE DATTHA INSTITUTE OF PHARMACY 10

11. STERIC PARAMETERS
• It is a measure of the bulkiness of the group it represents and it
effects on the closeness of contact between the drug and receptor
site
• Bulky substituent may help to orient a drug property for maximum
binding and increase activity.
SREE DATTHA INSTITUTE OF PHARMACY 11

12. 1. Taft’s steric factor/constant (Es):
• It is measured by the comparing the rate of hydrolysis of substituted
aliphatic esters against a standard ester under acidic condition
SREE DATTHA INSTITUTE OF PHARMACY 12
/

13. 2. Verloop Steric Parameter:
• Calculated by software STERIMOL
• Gives dimensions of substituent from the standard bond angle,
vander waals radii, bond length.
SREE DATTHA INSTITUTE OF PHARMACY 13

14. THANK YOU
SREE DATTHA INSTITUTE OF PHARMACY 14