Hope you I'll know about Electronic Parameters of Drugs.If you need more information please refer some books.

1. PHYSIOCHEMICALAND
ELECTRONIC PARAMETERS
USED TO QUANTIFY DRUG
ACTION
SUBMITTED BY
K. VISALI
2ND M.Sc., BIOTECHNOLOGY
ANNAMALAI UNIVERSITY

2. CONTENT
 Introduction
 Physiochemical parameter
 Topliss scheme
 Scheme for aliphatic side chain substituent
 Electronic parameter
 Hammett substituent constant
 Reference

3. INTRODUCTION
 DRUG – any substance or product that is used or intended to be
used to modify or explore physiological symptoms or pathological
systems or pathological state for the benefit of the recipient
 DRUG ACTION – interaction of drug molecules with receptors or
targets which produce normal or abnormal physiological processes
 These are quantify by using some parameters like physiochemical,
lipophilic parameter, steric parameter and electronic parameter

4. PHYSIOCHEMICAL PARAMETER
 Th ability of a chemical compound to elicit a pharmacological or
therapeutic effect is related to the influence of various
physiochemical properties of the chemical substance on biomolecule
that it interact with
 This can be determined by some methods like;
Hansch equation
Craig plot
Topliss scheme

5. TOPLISS SCHEME
 It is a flow diagram
 Two schemes
• Aromatic substituents (vinblastin)
• Aliphatic side chain substituent (vinica alkaloid)
 Depends on hydrophobicity and electronic factors and designed the optimum
substituent found effectively
 But not full replacement, once suitable number of structure have been
synthesized

6.  Aromatic substituents – lead compound tested for biological activity
and a monosubstituted aromatic ring
 First analogue – 4-chloro derivative, easy to synthesize
 More hydrophobic and electron withdrawing than hydrogen and π
and σ are positive
 Biological activity measured
 Three possibilities:
1. Less activity (L)
2. Equal activity (E)
3. More activity (M)

7. SCHEME FOR ALIPHATIC SIDE-CHAIN
SUBSTITUENTS

8. ELECTRONIC PARAMETER
 It has effects of various substituents have clear effect on drug’s
ionization or polarity
 In turn, may have effect on how easily a drug can pass through a
cell membranes (ionization) or how strongly it can interact with a
binding site (polarity)
 Used to measure electronic effect
 It can be determine by Hammett constant, dipole moment

9. HAMMETT SUBSTITUENT CONSTANT(σ)
 As far as substituents on an aromatic ring are concerned, the
measure used is known as the Hammett substituent constant(σ)
 Measure of electron withdrawing or electron-donating ability
 Determined by measuring the dissociation of a series
 For example, substituted benzoic acid (weaker acid) compared with
dissociation of benzoic acid itself (larger Kx)
 Substituent is present equilibrium affected

10.  Aromatic ring having a stronger electron withdrawing and
stabilizing influence on the carboxylate anion
 Equilibrium `will shift more to ionized form (if left indicates weaker
acid with smaller Kx)
 If substituent X is an electron donating group (alkyl group), then
aromatic ring is less able to stabilize carboxylate ion
 Larger Kx = σx positive (Cl, CF3)
 Smaller Kx = σx negative (Me)
 Constant H is zero

11.  It takes both resonance and inductive effects
 The σ of substituent depends on meta(σm) or para(σp)
 Example σp = 0.78 and σm = 0.71
 In meta position, the electron withdrawing power – inductive
influence
 In para position, both inductive and resonance but para value is
greater

12. REFERENCE
 Introduction to medicinal chemistry by GRAHAM L PATRICK
 Fundamental of medicinal chemistry by GARETH THOMAS
 www.slideshare.net/nehla313/qsar.com
 www.slideshare.net/OmarSokkar/.in