Electronic Parameters used for quantifying Drug - Introduction

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

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

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

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

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

 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)

SCHEME FOR ALIPHATIC SIDE-CHAIN
SUBSTITUENTS

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

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

 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

 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

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

Electronic Parameters used for quantifying Drug - Introduction

Electronic Parameters used for quantifying Drug - Introduction

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