Medicinal chemistry involves the discovery and design of new therapeutic chemicals and their development into medicines and drugs. It is an interdisciplinary field combining chemistry and biology. Medicinal chemists work to design new drug compounds, determine their biological effects, optimize their structures for desired effects and minimal side effects, and study how the body processes drugs. The physicochemical properties of drugs, like solubility, acidity, and reactivity influence their biological actions and interactions with targets in the body. Understanding these properties helps predict drugs' behaviors and design new candidates. A drug's solubility is key to its formulation and absorption in the body. Both lipophilic and hydrophilic structural features impact a molecule's solubility profile. Acidity and
This is the presentation for B. Pharm. IV semester students.
It includes Introduction of Medicinal Chemistry, History and Development of Medicinal Chemistry
This is the presentation for B. Pharm. IV semester students.
It includes Introduction of Medicinal Chemistry, History and Development of Medicinal Chemistry
1)Physical Properties
Physical property of drug is responsible for its action
2)Chemical Properties
The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
Role of Pharmacognosy in various systems of medicineRamaiah Maddi
Role of Pharmacognosy in Allopathy (Modern medicine)
Role of Pharmacognosy in Ayurveda
Role of Pharmacognosy in Unani System of Medicine
Role of Pharmacognosy in Siddha System of Medicine
Role of Pharmacognosy in Homeopathy
Role of Pharmacognosy in Chinese Medicine System
Physico-chemical Properties in Relation of Drug actionPradnya Gondane
This is the presentation for B. Pharm. IV semester students. It includes all the physico-chemical properties which affect drug action like solubility, ionization, pH, pKa, Protein Binding, Chelation, Hydrogen Bonding, Partition Coefficient and steric factors which includes, optical, conformational and bio isosters. This is prepared according to the PCI syllabus for B. Pharm. IV Semester students for Subject Medicinal Chemistry-I
DEFINITION:
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties
Physical property of drug is responsible for its action 2)Chemical Properties
The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
Various Physico-Chemical Properties are,
Solubility Partition Coefficient
Dissociation constant Hydrogen Bonding Ionization of Drug Redox Potential Complexation Surface activity Protein binding Isosterism
1. Solubility:
• The solubility of a substance at a given temperature is defined as the concentration of the dissolved solute, which is in equillibrium with the solid solute.
• Solubility depends on the nature of solute and solvent as well as temperature , pH & pressure.
• The solubility of drug may be expressed in terms of its affinity/philicity or repulsion/phobicity for either an aqueous or organic solvent.
The atoms and molecules of all organic substances are held together by various types of bonds (e.g. hydrogen bond, dipole –dipole, ionic bond etc.)
These forces are involved in solubility because it is the solvent-solvent, solute-solute, solvent-solute interactions that governs solubility.
Methods to improve solubility of drugs
1) Structural modification (alter the structure of molecules) 2) Use of Cosolvents (Ethanol, sorbitol,PPG,PEG)
3) Employing surfactants 4) Complexation
Importance of solubility
1. Solubility concept is important to pharmacist because it govern the preparation of liquid dosage form and the drug must be in solution before it is absorbed by the body to produce the biological activity.
2. Drug must be in solution form to interact with receptors.
Unit i.Optical Isomerism as per PCI syllabus of POC-III Ganesh Mote
Unit I optical isomerism which is included in PCI syllabus of Sem IV of POC-III subject
This Unit Includes all points of Unit I such as nomenclature, R& S, d&l, D& L isomerism, Meso compounds, diastereomers, chirality, resolution of racemic mixture, enantiomers, Asymmetric synthesis,
Medicinal plants have been identified and used throughout human history. Plants make many chemical compounds that are for biological functions, including defence against insects, fungi and herbivorous mammals. At least 12,000 such compounds have been isolated so far; a number estimated to be less than 10% of the total.Chemical compounds in plants mediate their effect on the human body through processes identical to those already well understood for the chemical compounds in conventional drugs; thus herbal medicines do not differ greatly from conventional drugs in terms of how they work. it is important to know various factors that affects medicinal plant cultivation.
1)Physical Properties
Physical property of drug is responsible for its action
2)Chemical Properties
The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
Role of Pharmacognosy in various systems of medicineRamaiah Maddi
Role of Pharmacognosy in Allopathy (Modern medicine)
Role of Pharmacognosy in Ayurveda
Role of Pharmacognosy in Unani System of Medicine
Role of Pharmacognosy in Siddha System of Medicine
Role of Pharmacognosy in Homeopathy
Role of Pharmacognosy in Chinese Medicine System
Physico-chemical Properties in Relation of Drug actionPradnya Gondane
This is the presentation for B. Pharm. IV semester students. It includes all the physico-chemical properties which affect drug action like solubility, ionization, pH, pKa, Protein Binding, Chelation, Hydrogen Bonding, Partition Coefficient and steric factors which includes, optical, conformational and bio isosters. This is prepared according to the PCI syllabus for B. Pharm. IV Semester students for Subject Medicinal Chemistry-I
DEFINITION:
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties
Physical property of drug is responsible for its action 2)Chemical Properties
The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
Various Physico-Chemical Properties are,
Solubility Partition Coefficient
Dissociation constant Hydrogen Bonding Ionization of Drug Redox Potential Complexation Surface activity Protein binding Isosterism
1. Solubility:
• The solubility of a substance at a given temperature is defined as the concentration of the dissolved solute, which is in equillibrium with the solid solute.
• Solubility depends on the nature of solute and solvent as well as temperature , pH & pressure.
• The solubility of drug may be expressed in terms of its affinity/philicity or repulsion/phobicity for either an aqueous or organic solvent.
The atoms and molecules of all organic substances are held together by various types of bonds (e.g. hydrogen bond, dipole –dipole, ionic bond etc.)
These forces are involved in solubility because it is the solvent-solvent, solute-solute, solvent-solute interactions that governs solubility.
Methods to improve solubility of drugs
1) Structural modification (alter the structure of molecules) 2) Use of Cosolvents (Ethanol, sorbitol,PPG,PEG)
3) Employing surfactants 4) Complexation
Importance of solubility
1. Solubility concept is important to pharmacist because it govern the preparation of liquid dosage form and the drug must be in solution before it is absorbed by the body to produce the biological activity.
2. Drug must be in solution form to interact with receptors.
Unit i.Optical Isomerism as per PCI syllabus of POC-III Ganesh Mote
Unit I optical isomerism which is included in PCI syllabus of Sem IV of POC-III subject
This Unit Includes all points of Unit I such as nomenclature, R& S, d&l, D& L isomerism, Meso compounds, diastereomers, chirality, resolution of racemic mixture, enantiomers, Asymmetric synthesis,
Medicinal plants have been identified and used throughout human history. Plants make many chemical compounds that are for biological functions, including defence against insects, fungi and herbivorous mammals. At least 12,000 such compounds have been isolated so far; a number estimated to be less than 10% of the total.Chemical compounds in plants mediate their effect on the human body through processes identical to those already well understood for the chemical compounds in conventional drugs; thus herbal medicines do not differ greatly from conventional drugs in terms of how they work. it is important to know various factors that affects medicinal plant cultivation.
A presentation given by a group of students of Faculty of Pharmacy, University of Dhaka, Bangladesh.
This presentation discussed with different physiolgical factors of drug absorption, structure of membrane the drug crosses, different transport mechanism etc
This is a ppt on Medicinal chemistry, just made to help out and give the students of CLASS XI studying in CBSE about what Medicinal Chemistry is >>Please do feedback in the comments part
relating to the process of providing or obtaining the food necessary for health and growth.
"genetic engineering can alter the nutritional value of food"
General pharmacology and pharmocokineticsSwapnil Singh
Basic pharmacology and Pharmacokinetics principles and concepts covering routes of drug administration, absorption phenomena, metabolism and excretion from the body.
Phsicochemical properties according to pci syllubus.
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties : Physical property of drug is responsible for its action
2)Chemical Properties :The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties : Physical property of drug is responsible for its action
2)Chemical Properties :The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
Physico chemical properties of drugs-convertedN J V S Pavan
this presentation is about the physico-chemical properties of a drug which are the reason for the drug's therapeutic effects and pharmacokinetics , pharmacodynamics ...
the information in the presentation is very much useful for the b.pharm 4th sem students .
Students can easily understand the concept as the presentation contains many examples
Investigate and quantify effects of toxicants on individual organisms
By definition is the amount of a substance administered at one time
However, other parameters are needed to characterize the exposure to xenobiotics. The most important are the number of doses, frequency, and total time period of the treatment.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
Honest Reviews of Tim Han LMA Course Program.pptxtimhan337
Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
Palestine last event orientationfvgnh .pptxRaedMohamed3
An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
2. 2
Introduction to Medicinal Chemistry
Medicinal chemistry is best to be defined as an
interdisciplinary research area incorporating different branches of
chemistry and biology in the research for better and new drugs
(Drug Discovery).
In other words, medicinal chemistry is the science, which
deals with the discovery and design of new and better
therapeutic chemicals and development of these chemicals into
new medicines and drugs.
Generally Medicinal Chemists can:
•Make new compounds
•Determine their effect on biological processes.
•Alter the structure of the compound for optimum effect and
minimum side effects.
•Study uptake, distribution, metabolism and excretion of drugs.
3. 3
Pure organic compounds are the chief source of agents for the cure,
mitigation or the prevention of disease.
These remedial agents could be classified according to their
origin:
• Natural compounds: materials obtained from both plant and
animal, e.g. vitamins, hormones, amino acids, antibiotics, alkaloids,
glycosides…. etc.).
• Synthesis compounds: either pure synthesis or synthesis
naturally occurring compounds (e.g. morphine, atropine, steroids and
cocaine) to reduce their cost.
• Semi-synthesis compounds: Some compounds either can not be
purely synthesized or can not be isolated from natural sources in low
cost. Therefore, the natural intermediate of such drugs could be used
for the synthesis of a desired product (e.g. semi synthetic penicillins).
Drug Classification
4. 4
Drug Classification
Since there is no certain relation between chemical structure and
pharmacological activity therefore, it would be unwise to arrange
all drugs on the basis of their structures or origin. Thus, it is better
to arrange the drugs according to their medicinal use.
Drugs can be classified according to their medicinal uses
into two main classes:
I-Pharmacodynamic agents: Drugs that act on the various
physiological functions of the body (e.g. general anaesthetic,
hypnotic and sedatives, analgesic etc.).
II-Chemotherapeutic agents: Those drugs which are used
to fight pathogenic (e.g. sulphonamides, antibiotics, antimalarial
agents, antiviral, anticancer etc.).
5. 5
Drug Classification
Drugs can treat different types of diseases:
1-Infectious diseases: Born (transmitted) from person to
person by outside agents, bacteria (pneumonia, salmonella),
viruses (common cold, AIDS), fungi (thrush, athletes foot),
parasites (malaria)
2-Non-infectious diseases: disorders of the human body
caused by genetic malfunction, environmental factors, stress,
old age etc. (e.g. diabetes, heart disease, cancer.
Haemophilia, asthma, mental illness, stomach ulcers, arthritis).
3-Non-diseases: alleviation of pain (analgesic), prevention of
pregnancy (contraception) , anesthesia.
6. 6
Physico-chemical properties in relation to
biological action
Drug action results from the interaction of drug molecules with either
normal or abnormal physiological processes.
Drugs normally interact with targets (which they are proteins, enzymes,
cell lipids, or pieces of DNA or RNA).
The ability of a chemical compound to elicit a pharmacologic
/therapeutic effect is related to the influence of its various physical and
chemical (physicochemical) properties
The most pharmacologically influential physicochemical properties of
organic medicinal agents (OMAs) are:
1.Solubility
2.Acidity and basicity
3.Reactivity
7. 7
1- SOLUBILITY OF ORGANIC MEDICINAL
AGENTS
Importance of solubility:
(1) Formulation of the drug in an appropriate dosage
form and
(2) Bio-disposition: Disposition of OMAs in the living
system after administration (absorption, distribution,
metabolism, and excretion).
The solubility expression: in terms of its affinity/philicity or
repulsion/phobicity for either an aqueous (hydro) or lipid (lipo)
solvent.
♣hydrophilic....................water loving
♣lipophobic.....................lipid hating
♣lipophilic.......................lipid loving
♣hydrophobic..................water hating
8. 8
1- SOLUBILITY OF ORGANIC MEDICINAL
AGENTS
Majority of OMAs possess balanced solubility (have
some degree of solubility in both aqueous and lipid
media).
Because there is a need for OMAs to move through
both aqueous (plasma, extracellular fluid,
cytoplasm, etc.) and lipid media (biologic
membranes) in the biological system.
9. 9
1- SOLUBILITY OF ORGANIC MEDICINAL AGENTS
Solubility of OMAs should be viewed as being on a continuum between high
lipophilicity on one end of the spectrum and high hydrophilicity on the other.
Lipophilic Hydrophilic
Equally soluble
OMAs
More lipophilic
OMAs
More hydrophilic
OMAs
In order for a chemical compound to dissolve in a particular
solvent/medium the compound must establish attractive forces
between itself and molecules of the solvent.
10. 10
1- SOLUBILITY OF ORGANIC MEDICINAL AGENTS
In order for a chemical compound to dissolve in a particular
solvent/medium the compound must establish attractive forces
between itself and molecules of the solvent.
It is possible to estimate the solubility properties of an OMA
(hydrophilic vs. lipophilic) by examining the structure of the
OMA and noting whether its structural features promote affinity
for aqueous or lipid media.
The most important intermolecular attractive forces (bonds)
that are involved in the solubilization process are:
11. 11
The most important intermolecular attractive forces (bonds)
that are involved in the solubilization process are:
1. Van der Waals Attraction
■weakest intermolecular force (0.5-1.0 kcal/mole)
■electrostatic
■occurs between nonpolar groups (e.g. hydrocarbons)
■highly distance and temperature dependent
2. Dipole-Dipole Bonding
■stronger (1.0 to 10 kcal/mole)
■occurs electrostatically between electron deficient and electron
excessive /rich atoms (dipoles)
■hydrogen bonding is a specific example of this bonding and serves as a
prime contributor to hydrophilicity
N: H O
H
δ−
C
O
O H
O
H
H
δ− δ+
δ+
δ+
δ−
12. 12
3.Ionic Bonding
■electrostatic attraction between cations and anions
■common in inorganic compounds and salts of organic
molecules
■relatively strong (5 kcal/mole)
4.Ion-Dipole Bonding
■electrostatic between a cation/anion and a dipole
■relatively strong (1-5 kcal/mole)
■low temperature and distance dependence
■important attraction between OMAs and H2O
N
+
H Cl
- C
O
O
-
Na
+
N
+
H
O
H
H
δ
−
C
O
O
-
H
O
H
δ
+
13. 13
Solubility Prediction
The relative solubility of an OMA is a function of
the presence of both lipophilic and hydrophilic
features within its structure, which serve to
determine the extent of interaction of the OMA with
lipid and/or aqueous phases.
The relative solubility of an OMA can be
determined in the laboratory, i.e. the partition
coefficient [P; the ratio of the solubility of the
compound in an organic solvent to the solubility of
the same compound in an aqueous environment
(i.e., P=[Drug]lipid/ [Drug]aqueous). P is often
expressed as a log value.
14. 14
Solubility Prediction
A mathematical procedures also have been
developed to estimate the relative solubility of an
organic molecule based upon differential
contributions of various structural features to overall
solubility.
For example, the relative solubility of an OMA is the
sum of the contributions of each group and
substituent to overall solubility.
Example:
Examination of the structure of chloramphenicol
(indicates the presence of both lipophilic (nonpolar)
and hydrophilic (polar) groups and substituents.
15. 15
The presence of oxygen and nitrogen containing functional groups
usually enhances water solubility. While lipid solubility is enhanced by
nonionizable hydrocarbon chains and ring systems.
CHO2N
OH
CH
CH2OH
NH C
O
CHCl2
Lipophilic
Lipophilic
Hydrophilic
Hydrophilic
Hydrophilic
Chloramphenicol
Solubility Prediction
16. 16
1.Laboratory Estimation of Relative Solubility
The relative solubility of an organic compound is measured by determining the
extent of its distribution into an aqueous solvent (usually pH 7.4 buffer) and a
lipid solvent (usually n-octanol). These experiments generate a value, P, the
partition coefficient for that particular compound.
Partition coefficient =
Conc. of compunds in C8H16OH
Conc. of compunds in H2O
Solubility Prediction
17. 17
2- Mathematical Estimation of Relative Solubility
Solubility contributions (groups and substituents) are expressed as
hydrophilic (negative value) or lipophilic (positive value) fragment
constants. Log Pcalc = Σπ
Where; Log Pcalc = log of partition cofficient and Σπ= sum of hydrophilic-
lipophilic constants.
Hydrophilic-Lipophilic constants.
Fragment
π Value
C (aliphatic) +0.5
C6H5- +2.0
Cl +0.5
O2
NO +0.2
Intramolecular hydrogen bonding (IMHB) +0.65
S +0.5
O=C-O -0.7
O=C-N -0.7
O(hydroxyl, phenyl, ether) -1.0
N (amine) -1.0
O2
N (aliphatic) -0.85
O2
N (aromatic) -0.28
18. 18
Calculation steps of Log P for OMA
(i) The molecule is dissected into its various groups, functionalities and
substitutents
(ii) Appropriate hydrophilic/lipophilic fragment constants are assigned and
summed
(iii) Compounds with log Pcalc values greater than +0.5 are considered
water insoluble (lipophilic) and those with log Pcalc values less than
+0.5 are considered water soluble (hydrophilic).
COOH
OH
COOH
OH
Salicylic acid
p-Hydroxybenzoic acid
Calculated log P Values for salicylic acid and p-Hydroxybenzoic acid:
Salicylic acid p-Hydroxybenzoic acid
Fragment π Value Fragment π Value
Phenyl +2.0 Phenyl +2.0
OH -1.0 OH -1.0
COOH -0.7 COOH -0.7
IMHB +0.65 - -
Sum +0.95 +0.3
Prediction Water insoluble Prediction Water soluble
19. 19
Quantitative Structure Activity
Relationship (QSAR)
As shown we can estimate the relative solubility of drugs on the
basis of the structure features.
However, there is a relationship between the quantity of the drug that
binds to the active site and its structure and thus, the biological activity.
This relationship is called quantitative structure activity relationship
(QSAR).
QSAR can be used:
1- To predict the design of new compounds and
2- To reduce the types of chemical process involved in the biological activity.
Because, the biological activity of substances is related to oil water
distribution coefficient (distribution of the compound between the aqueous and
the lipid phases of the tissue), which is an important parameter for solubility
and thus the quantity of the drugs that binds to the active site.
20. 20
2- Acidity and Basicity
Acidic and/or basic properties of OMAs are important in both:
1- Pharmaceutical phase (dosage formulation, etc.) and
2- Pharmacological phases (disposition, structure at target site, etc.).
The three aspects of acid-base chemistry:
(1) Definitions
(2) Recognition of acidic or basic organic functional groups and
(3) An estimation of the relative acid/base strength of these groups.
Definitions:
Acid: An organic compound containing a functional group that can donate a proton (H+)
Base: An organic compound that contains a functional group that can accept a H+
21. 21
2- Recognition of acidic or basic organic functional
groups
1- Common acidic organic functional groups
◙Carboxylic acid (-COOH)
◙Phenol (Ar-OH)
◙Sulfonamide (R-SO2NH2)
◙Imide (R-CO-NH-CO-R)
◙β-Carbonyl group (-CO-CHR-CO-)
R C
O
O H
+ H2O R C
O
O-
+ H3O
+
O
H
R + H2O
O
-
R
Carboxylic acid
Phenol
H3O
+
R
NH3
+
H2O+
NH2
R
+
H3O
+
+
Anilinium cation
R SO2NH2
H3O
+
+H2O+ R SO2NH
-
Sulfonamide
R
O
N
O
R
H + H2O +
R
O
N-
O
R
H3O
+
Imide
22. 22
2-Recognition of acidic or basic organic functional
groups(cont)
2- Common basic organic functional groups
◙Aliphatic 1º (R-NH2), 2º (R2NH) and 3º (R3N)-amines
◙Heterocyclic amines
◙Aromatic amines (Ar-NH2)
R N
R
R
+ H3O+
H2O+R N
+
R
R
H
+ H2OH3O+
+
N N+
R
Aliphatic amines
Heteroaromatic amines
NH3
+
NH2
+ H3O
+ H2O+
Aromatic amines
N N
H
N NH
Pyridine
Piperidine
Imidazole
23. 23
Estimation of the Relative Acid/Base Strength
The ionization constant (ka) indicates the relative strength of the acid or base.
An acid with a ka of 1x10-3 is stronger acid (more ionized) than one with a ka of 1x10-5
A base with a ka of 1x10-7 is weaker (less ionized) than one with a ka of 1x10-9
The negative log of the ionization constant (pka) also indicates the relative strength of
the acid or base.
An acid with a pka of 5 (ka=1x10-5) is weaker (less ionized) than one with pka of 3
Whereas a base with a pka of 9 is stronger (more ionized) than one with a pka of 7
E.g. Ionization of weak acid (e.g. acetic acid, pka =4.76) is as follows:
CH3COOH CH3COO
-
H
+
+
NH4
+
+ H2O NH3 + H3O+
24. 24
Estimation of the Relative Acid/Base Strength
H2SO4, HCl, HNO3, H3O
+
, RCO2H, ArOH, RSO2NH2, CONHCO , H2O, ArNH2, RNH2, NaOH/KOH
INCREASEING ACIDITY
INCREASING BASICITY
ACIDS BASES
The following chart is comparing acid/base strengths:
25. 25
The following chart is comparing acid strengths of various functional
groups ACID NAME ACIDITY pKa
RSO3
H Sulfonic acid 1
RCOOH Carboxylic acid 4.5
ArSO2
NHR Aromatic sulfonamide 6-9
ArOH Phenol 8-11
Imide 8-10
The following chart is comparing base strengths of various functional
groups
ACID NAME Basicity pKa
RNH2
, R2
NH, R3
N Aliphatic amines 3-4
ArNH2
Aromatic amines 9-13
Pyridine, piperidine,
imidazole
Heterocyclic amines 4-12
R
O
N
O
R
H
26. 26
Ionization of Acidic and Basic Functional
Groups
I-Acids
Imides
H3O+
R
O
N
-
O
R
+H2O+
R
O
N
O
R
H
Sulfonamides
R SO2NH-
+ H2O
+ H3O+
+ H3O+
Phenols
Carboxylic acids
O-
H2O+
O
H
H3O+
+R C
O
O-H2O+R C
O
O H
ArSO2NHR
Aromatic amines
+ H2OH3O
+
+
NH2 NH3
+
Heteroaromatic amines
Aliphatic amines
N
+
R
N
+ H3O
+ H2O+
R N+
R
R
H+ H2OH3O
+
+R N
R
R
II-Bases
27. 27
Acidic and Basic Functional Group - Salt
Formation
Salt: is the combination of an acid and a base
All salts are strong electrolytes (with few exceptions: mercuric and cadmium
halides and lead acetate)
The salt form of the drug is more soluble than its parent molecule
Drug salts can be divided into two classes:
1) Inorganic salts: are made by combining drug molecules with inorganic
acids and bases, such HCl, H2SO4, KOH and NaOH. Inorganic salts are
generally used to increase the aqueous solubility of a compound
2) Organic salts: are made by combining two drug molecules, one acidic
and one basic. The salt formed by this combination has increased lipid
solubility and generally is used to make depot injections (e.g. procaine
penicillin).
NaOH+RCOOH H2O+RCOO
-
Na
+
R3NH
+
Cl
-
R3N + HCl
Sodium salt formation from carboxylic acid:
Hydrochloric salt formation from an aliphatic amine
28. 28
Structurally Non-Specific and Specific Activity
Drug activity can be classified as
(a)Structurally non-specific or
(b) Structurally specific
1-Structurally non-specific activity is dependent on physical
properties like solubility, partition coefficients and vapour pressure and
not on the presence or absence of some chemical group.
Substances such as alkanes, alkenes, alkynes, alcohols, amides, ethers,
ketones and chlorinated hydrocarbons exhibit narcotic activity and
potency of each substance is related to its partition coefficient.
Structurally non-specific action results from accumulation of a drug in some
vital part of a cell with lipid characteristics.
The structurally non-specific drugs include general anaesthetics, hypnotics together
with a few bactericidal compounds and insecticides.
29. 29
Structurally Non-Specific and Specific Activity
2-Structurally specific activity is dependent upon factors such as the
presence or absence of certain functional groups, intramolecular distance,
and shape of the molecules.
Activity is not easily co-related with any physical property and small changes in
structure often lead to changes in activity.
Structurally specific activity is dependent upon the interaction of the drug with a
cellular receptor.
30. 30
Drug-receptor Interaction
Receptor is the site in the biological system where the drug exerts its
characteristic effects or where the drug acts.
Receptors have an important regulatory function in the target organ or tissue.
Most drugs act by combining with receptor in the biological system (specific
drugs).
1-cholinergic drugs interacts with acetylcholine receptors.
2-synthetic corticosteroids bind to the same receptor as cortisone and
hydrocortisone
3-non steroidal anti inflammatory drugs inhibit cyclooxygenase enzyme that will
inhibit the formation of prostaglandins which will lead to inflammation symptoms.
Non-specific drugs do not act upon receptors.
The receptor substance is considered mostly to be a cellular constituent. Recent
studies, however, indicate that the receptors are proteins or enzymes.
The ability of a drug to get bound to a receptor is termed as the affinity of the drug
for the receptor.
31. 31
Drug-receptor Interaction
The ability of a drug to get bound to a receptor is termed as the affinity of the drug for
the receptor.
The receptors are also dynamic in nature and have a special chemical affinity and
structural requirements for the drug. Thus, affinity represents kinetic constants
that relate to the drug and the receptor.
The drug elicits a pharmacological response after its interaction with the receptor.
A given drug may act on more than one receptor differing both in function and in
binding characteristics (non-selective drugs).
There are also many factors effect changes in receptor concentration and/or
affinity.
A drug, which initiates a pharmacological action after combining with the receptor,
is termed agonist.
Drugs which binds to the receptors but are not capable of eliciting a
pharmacological response produce receptor blockage, these compounds are
termed antagonists.
32. 32
Structural features of drugs and their
pharmacological activity
Stereochemistry: Space arrangement of the atoms or three-
dimensional structure of the molecule.
Stereochemistry plays a major role in the pharmacological properties
because:
(1) Any change in stereospecificity of the drug will affect its
pharmacological activity
(2) The isomeric pairs have different physical properties (partition
coefficient, pka, etc.) and thus differ in pharmacological activity.
The following steric factors influence pharmacological activity:
● Optical and geometric isomerism
● Conformational isomerism
● Isosterism and bioisosterism
33. 33
Structural features of drugs and their
pharmacological activity
I-Optical and geometric isomerism and pharmacological
activity
Optical isomers are compounds that contain at least one chiral
carbon atom or are compounds that differ only in their ability to
rotate the pollarized light.
The (+) or dextrorotatory: isomer rotates light to the right
(clockwise). The (-) or levorotatory: isomer rotates light to the
left (counterclockwise).
34. 34
Enantiomers (optical isomers) can have large differences in
potency, receptor fit, biological activity, transport and metabolism.
For example, levo-phenol has narcotic, analgesic, and antitussive
properties, whereas its mirror image, dextro-phenol, has only
antitussive activity.
CH3
OH
HH3C
CH3
H CH3
OH
2-Hydroxybutane enantiomers (mirror images can not superimposed)
35. 35
Geometric isomerism (cis-trans isomerisms).
Occur as a result of restricted rotation about a chemical bond, owing to
double bonds or rigid ring system in the molecule.
They are not mirror images and have different physicochemical properties
and pharmacological activity. Because different distances separate the
functional groups of these isomers.
They generally do not fit to the same receptor equally well and if these
functional groups are pharmacophores the isomers will differ in biologic
activity.
For example, cis-diethylstilbestrol has only 7% of the oestrogenic activity of
trans- diethylstilbestrol
OHHO HO
OH
Cis-diethylstilbestrol Trans-diethylstilbestrol
36. 36
II- Conformational isomersim and
pharmacological activity
Conformational isomersim is the non-identical space arrangement of
atoms in a molecule, resulting from rotation about one or more single bonds.
Almost every drug can exist in more than one conformation and thus the drug
might bind to more than one receptor but a specific receptor site may bind
only to one of many conformations of a drug molecule.
For example, the trans conformation of acetylcholine binds to the
muscarinic receptor, where as the gauche conformation binds to the
nicotinic receptor.
N
+
HH
H
H
OAc
(CH3)3 N
+
HH
OAc
H
H
(CH3)3
Trans Gauche
Conformations of acetylcholine
37. 37
III- Isosterism, Bioisosterism and
pharmacological activity
Isosterism: Any two ions or molecules having an identical number and
arrangement of electrons
(e.g. CO and NO2;
CO2(O=C=O) and N2O (
-
N=N+
=O N= N+
O) ;
and N-3 and NCO- etc.).
Bioisosterism is the procedure of the synthesis of structural analogues of a
lead compound by substitution of an atom or a group of atoms in the parent
compound for another with similar electronic and steric characteristics.
Bioisosetres are functional groups which have similar spatial and electronic
character, but they retain the activity of the parent.
Bioisosterism is important in medicinal chemistry because:
1-Maintain similar biological properties.
2-Resolved biological problems effectively (potency, side effects, separate
38. 38
III- Isosterism and pharmacological
activity
Friedman defined bio-isosterism as- the phenomenon by
which compounds usually fit the broadest definition of isosteres
and possess the same type of biological activity.
E.g. (Antihistamine; A; B and C)
CHO CH2CH2 N CHO CH2CH2 N
CH2CH3
CH2CH3
CHO CH2CH2 N
CH3
CH3
A B C
Compound A has twice the activity of C, and many times greater than B