This document discusses the role of chirality in selective therapeutic agents. It begins by defining isomerism and the different types of isomers including constitutional, stereoisomers, optical isomers, enantiomers, and diastereomers. It then discusses the discovery of optical activity and chirality. The key points are that humans are chiral beings and the enantiomers of chiral drugs may have different biological effects. Several examples are given to illustrate how the biological activity of enantiomers can differ, including some being more active, having opposing effects, or one causing toxicity. The importance of understanding chirality in drug development and safety is emphasized.
Stereochemistry is the ‘chemistry of space’ , that is stereochemistry deals with the spatial arrangements of atoms and groups in a molecule.
Stereochemistry can trace its roots to the year 1842 when the French chemist Louis Pasteur made an observation that the salts of tartaric acid collected from a wine production vessel have the ability to rotate plane-polarized light, whereas the same salts from different sources did not have this ability.
Isomers are compounds that contain exactly the same number of atoms, i.e., they have exactly the same empirical formula, but differ from each other by the way in which the atoms are arranged.
Constitutional isomers, also known as structural isomers, are specific types of isomers that share the same molecular formula but have different bonding atomic organization and bonding patterns.
Stereoisomers are molecules having the same molecular formula and the atomic arrangement, but differ in their spatial arrangement.
Geometric isomers are two or more coordination compounds which contain the same number and types of atoms, and bonds (i.e., the connectivity between atoms is the same), but which have different spatial arrangements of the atoms.
There are 2 types of geometric isomers, ‘cis’ and ‘trans’.-cis isomers: when similar groups are present on the same side of the double bonds, then they are termed as cis.- trans isomers: when similar groups are present on the opposite sides of the double bonds then they are called trans isomers.
cis-diethylstilbestrol has only 7% of the estrogenic activity of trans-diethylstilbesterol.
Cisplatin have anticancer activity where ae trans platin is an inactive compound.
In chemistry, a molecule or ion is called chiral if it cannot be superposed on its mirror image by any combination of rotations, translations, and some conformational changes.
Chirality is the property of being non identical to ones mirror image.
Chiral center is defined as the atom bearing 4 different atoms or group of atoms.
Molecules that form nonsuperimposable mirror images, and thus exist as enantiomers, are said to be chiral molecules.
For a molecule to be chiral, it cannot contain a plane of symmetry.
The term enantioselectivity refers to the efficiency with which the reaction produces one enantiomer.
Enantiomers are stereoisomers that are non-superimposable mirror images.
Have identical properties.
Similar shapes
Diastereomers are stereoisomers that are non superimposable and are not mirror images.
Have distinct physical properties.
Have different molecular shapes.
Enantiomers consist of a pair of molecules that are mirror images of each other and are not superimposable.
When a molecule contains only one chiral centre , the two stereoisomers are known as enantiomers.
These may be referred to or labelled using the configurational descriptors as either:
R(rectus meaning right handed) or S(sinister meaning left handed),
D(dextrorotatory)or L (laevorotatory)
E-Entgegen or Z- Zusamen
Active constituent of drugs used in diabetic therapyAkshay Kank
In this slide the active constituents which is isolated from herbal sources used for to treat the type 1 and type 2 diabetes is covered. 'Gymnema' and 'swerita chirata' herbal plant is also covered in the slide.This work help in to focus the herbal emphasis on diabetes.
Analog design is usually defined as the modification of a drug molecule or of any bioactive compound in order to prepare a new molecule showing chemical and biological similarity with the original model compound
Stereochemistry is the ‘chemistry of space’ , that is stereochemistry deals with the spatial arrangements of atoms and groups in a molecule.
Stereochemistry can trace its roots to the year 1842 when the French chemist Louis Pasteur made an observation that the salts of tartaric acid collected from a wine production vessel have the ability to rotate plane-polarized light, whereas the same salts from different sources did not have this ability.
Isomers are compounds that contain exactly the same number of atoms, i.e., they have exactly the same empirical formula, but differ from each other by the way in which the atoms are arranged.
Constitutional isomers, also known as structural isomers, are specific types of isomers that share the same molecular formula but have different bonding atomic organization and bonding patterns.
Stereoisomers are molecules having the same molecular formula and the atomic arrangement, but differ in their spatial arrangement.
Geometric isomers are two or more coordination compounds which contain the same number and types of atoms, and bonds (i.e., the connectivity between atoms is the same), but which have different spatial arrangements of the atoms.
There are 2 types of geometric isomers, ‘cis’ and ‘trans’.-cis isomers: when similar groups are present on the same side of the double bonds, then they are termed as cis.- trans isomers: when similar groups are present on the opposite sides of the double bonds then they are called trans isomers.
cis-diethylstilbestrol has only 7% of the estrogenic activity of trans-diethylstilbesterol.
Cisplatin have anticancer activity where ae trans platin is an inactive compound.
In chemistry, a molecule or ion is called chiral if it cannot be superposed on its mirror image by any combination of rotations, translations, and some conformational changes.
Chirality is the property of being non identical to ones mirror image.
Chiral center is defined as the atom bearing 4 different atoms or group of atoms.
Molecules that form nonsuperimposable mirror images, and thus exist as enantiomers, are said to be chiral molecules.
For a molecule to be chiral, it cannot contain a plane of symmetry.
The term enantioselectivity refers to the efficiency with which the reaction produces one enantiomer.
Enantiomers are stereoisomers that are non-superimposable mirror images.
Have identical properties.
Similar shapes
Diastereomers are stereoisomers that are non superimposable and are not mirror images.
Have distinct physical properties.
Have different molecular shapes.
Enantiomers consist of a pair of molecules that are mirror images of each other and are not superimposable.
When a molecule contains only one chiral centre , the two stereoisomers are known as enantiomers.
These may be referred to or labelled using the configurational descriptors as either:
R(rectus meaning right handed) or S(sinister meaning left handed),
D(dextrorotatory)or L (laevorotatory)
E-Entgegen or Z- Zusamen
Active constituent of drugs used in diabetic therapyAkshay Kank
In this slide the active constituents which is isolated from herbal sources used for to treat the type 1 and type 2 diabetes is covered. 'Gymnema' and 'swerita chirata' herbal plant is also covered in the slide.This work help in to focus the herbal emphasis on diabetes.
Analog design is usually defined as the modification of a drug molecule or of any bioactive compound in order to prepare a new molecule showing chemical and biological similarity with the original model compound
Contents includes at least three strategies of synthesis for each of three, four, five and six membered heterocylic ring with one or two heteroatoms. One mechanism described out of the three strategies. Few name reactions are described and the other are simple synthetic methods. This presentation was prepared for the partial fulfillment of Master of Pharmacy. The content was taken from the various books, mentioned in slide with the title of references.
Introduction
Classification
Therapeutic values of peptidomimetics
Design of peptidomimetics by manipulation of amino acids
Modification of peptide backbone
Chemistry of prostaglandins, leukotrienes and thromboxanes
Penicillin, one of the first and still one of the most widely used antibiotic agents, is derived from the penicillium mold. In 1928 Scottish bacteriologist alexander fleming in a contaminated green mold penicillium notatum. He isolated the mold, grew it in a fluid medium, and found that it produced a substance capable of killing many of the common bacteria that infect humans. Australian pathologist howard florey and British biochemist ernst Boris chain isolated and purified penicillin in the late 1930s, and by 1941 an injectable form of the drug was available for therapeutic use.
Penicillin's are beta lactam antibiotics and characterized by three fundamental structural requirements
The fused beta-lactam and thiazolidine ring structure.
free carboxylic acid group.
And one or more substituted acylamino side chain.
Penam nucleus: 7-oxo-l-thia-4-azabicyclo [3.2.0] heptane
Absolute configuration: 3-S, 5-R, 6-R.
Instrumental methods of characterization:
FTIR
MASS
C13-NMR
1H-NMR
FTIR: -
Penicillin G molecule and its IR spectra in D2 O and in DMSO. Spectra are characterized by the presence of three intense bands.
β- lactam CO stretching observe at 1761 cm-1 in D2O and 1762 cm-1 in DMSO solution.
Amide group is observe at 1640 cm-1 in D2O and 1674 cm-1 in DMSO solution.
Asymmetric stretching of carboxylate group is observe at 1601 cm-1 in D20 and 1615 cm-1 in DMSO solution.
A large red shift of amide , out of the frequency window, is observed upon proton exchange in DMSO.
Collision-Induced Dissociation (CID) technique
MASS:-
A high-resolution, hybrid tandem mass spectrometer was used to obtain CID spectra. The CID spectra were acquired by:
Mass selecting the precursor ions using the first mass spectrometer.
Injecting the ions into the first quadrupole (collision cell) where they undergo CID.
Mass-analyzing the fragment ions produced using the second quadrupole.
Argon was used as the collision gas, and the pressure in the collision cell was adjusted to attenuate the precursor ion intensity to 20-50% of the original intensity. The collision energy of the ions ranged from 160 to 180 eV. The mass spectra shown abundant fragmentations at m/z 160 and m/z 176 that were reported to arise from cleavage of the β-lactam ring.
protonated benzyl penicillin exhibits abundant fragment ions at m/z 160, m/z 176, m/z 217, m/z 128, and m/z 289. The most abundant CID fragment at m/z 160 and the molecular ion peak was observed at m/z 334.
C13-NMR: -
The four sp3 ring carbons give rise to resonances in the decreasing chemical shift order C-3, C-5, C-2 and C-6.
Chemical shift for C-2 is 64.9 ppm and the substituents attached with it are α-methyl 27.0 ppm and β-methyl 31.4 ppm. Chemical shift for C-3 is 73.6 ppm and 174.5 ppm for carboxylate functions (reflecting the smaller de-shielding influence of COOH over that of COO-). The chemic shift for C-5 is 67.2 ppm. The chemic shift for C-6 is 58.4 ppm.
The lactam group shows its chemical shift at 175.0 ppm
Amino group
Presented by Shikha Popali and Harshpal singh Wahi students from Gurunanak college of pharmacy, Nagpur in Department of pharmaceutical Chemistry. The explained topic is seful for every chemistry student and for others too
There are many ways that drug-resistant infections can be prevented: immunization, safe food preparation, handwashing, and using antibiotics as directed and only when necessary. In addition, preventing infections also prevents the spread of resistant bacteria.The main cause of antibiotic resistance is antibiotic use. When we use antibiotics, some bacteria die but resistant bacteria can survive and even multiply. The overuse of antibiotics makes resistant bacteria more common. The more we use antibiotics, the more chances bacteria have to become resistant to them.
Contents includes at least three strategies of synthesis for each of three, four, five and six membered heterocylic ring with one or two heteroatoms. One mechanism described out of the three strategies. Few name reactions are described and the other are simple synthetic methods. This presentation was prepared for the partial fulfillment of Master of Pharmacy. The content was taken from the various books, mentioned in slide with the title of references.
Introduction
Classification
Therapeutic values of peptidomimetics
Design of peptidomimetics by manipulation of amino acids
Modification of peptide backbone
Chemistry of prostaglandins, leukotrienes and thromboxanes
Penicillin, one of the first and still one of the most widely used antibiotic agents, is derived from the penicillium mold. In 1928 Scottish bacteriologist alexander fleming in a contaminated green mold penicillium notatum. He isolated the mold, grew it in a fluid medium, and found that it produced a substance capable of killing many of the common bacteria that infect humans. Australian pathologist howard florey and British biochemist ernst Boris chain isolated and purified penicillin in the late 1930s, and by 1941 an injectable form of the drug was available for therapeutic use.
Penicillin's are beta lactam antibiotics and characterized by three fundamental structural requirements
The fused beta-lactam and thiazolidine ring structure.
free carboxylic acid group.
And one or more substituted acylamino side chain.
Penam nucleus: 7-oxo-l-thia-4-azabicyclo [3.2.0] heptane
Absolute configuration: 3-S, 5-R, 6-R.
Instrumental methods of characterization:
FTIR
MASS
C13-NMR
1H-NMR
FTIR: -
Penicillin G molecule and its IR spectra in D2 O and in DMSO. Spectra are characterized by the presence of three intense bands.
β- lactam CO stretching observe at 1761 cm-1 in D2O and 1762 cm-1 in DMSO solution.
Amide group is observe at 1640 cm-1 in D2O and 1674 cm-1 in DMSO solution.
Asymmetric stretching of carboxylate group is observe at 1601 cm-1 in D20 and 1615 cm-1 in DMSO solution.
A large red shift of amide , out of the frequency window, is observed upon proton exchange in DMSO.
Collision-Induced Dissociation (CID) technique
MASS:-
A high-resolution, hybrid tandem mass spectrometer was used to obtain CID spectra. The CID spectra were acquired by:
Mass selecting the precursor ions using the first mass spectrometer.
Injecting the ions into the first quadrupole (collision cell) where they undergo CID.
Mass-analyzing the fragment ions produced using the second quadrupole.
Argon was used as the collision gas, and the pressure in the collision cell was adjusted to attenuate the precursor ion intensity to 20-50% of the original intensity. The collision energy of the ions ranged from 160 to 180 eV. The mass spectra shown abundant fragmentations at m/z 160 and m/z 176 that were reported to arise from cleavage of the β-lactam ring.
protonated benzyl penicillin exhibits abundant fragment ions at m/z 160, m/z 176, m/z 217, m/z 128, and m/z 289. The most abundant CID fragment at m/z 160 and the molecular ion peak was observed at m/z 334.
C13-NMR: -
The four sp3 ring carbons give rise to resonances in the decreasing chemical shift order C-3, C-5, C-2 and C-6.
Chemical shift for C-2 is 64.9 ppm and the substituents attached with it are α-methyl 27.0 ppm and β-methyl 31.4 ppm. Chemical shift for C-3 is 73.6 ppm and 174.5 ppm for carboxylate functions (reflecting the smaller de-shielding influence of COOH over that of COO-). The chemic shift for C-5 is 67.2 ppm. The chemic shift for C-6 is 58.4 ppm.
The lactam group shows its chemical shift at 175.0 ppm
Amino group
Presented by Shikha Popali and Harshpal singh Wahi students from Gurunanak college of pharmacy, Nagpur in Department of pharmaceutical Chemistry. The explained topic is seful for every chemistry student and for others too
There are many ways that drug-resistant infections can be prevented: immunization, safe food preparation, handwashing, and using antibiotics as directed and only when necessary. In addition, preventing infections also prevents the spread of resistant bacteria.The main cause of antibiotic resistance is antibiotic use. When we use antibiotics, some bacteria die but resistant bacteria can survive and even multiply. The overuse of antibiotics makes resistant bacteria more common. The more we use antibiotics, the more chances bacteria have to become resistant to them.
stereochemistry and drug action ; basic introduction about stereochemistry and stereoisomers ; pharmacokinetic and pharmacodynamics concept of stereochemistry ; easson Stedman hypothesis ; stereo selectivity criteria .
e-content of Stereochemistry for Pharmacy and Chemistry students.
contents includes Isomerism, Chirality, Stereoisomers, Enantiomer, Diastereomer, Cis And Trans Configuration ,L And D Configuration ,R And S Configuration and Importance of the chirality in drugs ,Intravenous anaesthetics , etc.
this presentation describes ways to enantiomeric product synthesis, hence introducing to chiral catalysts. the temperature effects are discussed with relation to soai autocatalysis. it shows introduction to stereocartography.
Enantiomers are a part and parcel of modern Drug discovery and development. Chiral drugs are largely replacing their earlier racemic as and when found suitable. It is my attempt to compile the basic concepts from various books, articles and online journals. Feel free to comment.
have reported the synthesis of a range of fluoroquinolone derivatives with 4-(carbopiperazin-1-yl)piperazinyl moieties at the C-7 position and the results indicated that a 7-[4-(4-(benzoyl)carbopiperazin-1-yl)]piperazinyl derivatives and two 7-[4-(4-(benzenesulfonyl)carbopiperazin-1-yl)]piperazinyl derivatives are showed more have synthesize novel 1,7-disubstituted-6-nitroquinolones. The new derivatives were tested against Mycobacterium tuberculosis and Mycobacterium avium complex (MAC) as well as against both Gram positive and Gram negative bacteria. Some derivatives were also found more potent
We all have good and bad thoughts from time to time and situation to situation. We are bombarded daily with spiraling thoughts(both negative and positive) creating all-consuming feel , making us difficult to manage with associated suffering. Good thoughts are like our Mob Signal (Positive thought) amidst noise(negative thought) in the atmosphere. Negative thoughts like noise outweigh positive thoughts. These thoughts often create unwanted confusion, trouble, stress and frustration in our mind as well as chaos in our physical world. Negative thoughts are also known as “distorted thinking”.
This is a presentation by Dada Robert in a Your Skill Boost masterclass organised by the Excellence Foundation for South Sudan (EFSS) on Saturday, the 25th and Sunday, the 26th of May 2024.
He discussed the concept of quality improvement, emphasizing its applicability to various aspects of life, including personal, project, and program improvements. He defined quality as doing the right thing at the right time in the right way to achieve the best possible results and discussed the concept of the "gap" between what we know and what we do, and how this gap represents the areas we need to improve. He explained the scientific approach to quality improvement, which involves systematic performance analysis, testing and learning, and implementing change ideas. He also highlighted the importance of client focus and a team approach to quality improvement.
The Indian economy is classified into different sectors to simplify the analysis and understanding of economic activities. For Class 10, it's essential to grasp the sectors of the Indian economy, understand their characteristics, and recognize their importance. This guide will provide detailed notes on the Sectors of the Indian Economy Class 10, using specific long-tail keywords to enhance comprehension.
For more information, visit-www.vavaclasses.com
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Students, digital devices and success - Andreas Schleicher - 27 May 2024..pptxEduSkills OECD
Andreas Schleicher presents at the OECD webinar ‘Digital devices in schools: detrimental distraction or secret to success?’ on 27 May 2024. The presentation was based on findings from PISA 2022 results and the webinar helped launch the PISA in Focus ‘Managing screen time: How to protect and equip students against distraction’ https://www.oecd-ilibrary.org/education/managing-screen-time_7c225af4-en and the OECD Education Policy Perspective ‘Students, digital devices and success’ can be found here - https://oe.cd/il/5yV
Ethnobotany and Ethnopharmacology:
Ethnobotany in herbal drug evaluation,
Impact of Ethnobotany in traditional medicine,
New development in herbals,
Bio-prospecting tools for drug discovery,
Role of Ethnopharmacology in drug evaluation,
Reverse Pharmacology.
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!
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.
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
Role of chirality in stereoselective and specific theraputic agent
1. PRESENTED BY
KARANVIR SINGH
M PHARM
(PHARMACEUTICAL CHEMISTRY)
ROLE OF CHIRALITY IN SELECTIVE AND SPECIFIC THERAPUTIC AGENTS
ISF COLLEGE OF PHARMACY
MOGA
2. ISOMERISM
Isomers by definition are the molecules of identical
atomic compositions (molecular formulas), but with
different bonding arrangements of atoms or orientation
of their atoms in space.The phenomenon is known as
Isomerism.
4. CONSTITUTIONAL ISOMERISM
These are also called structural or positional isomers are molecules with the
same atomic composition but different bonding arrangements between atoms.
Simple example of constitutional isomerism is given examples of catechol,
resorcinol, and hydroquinone all of these compounds having the same atomic
composition (C6H602), but different bonding arrangements of atoms. These are thus
distinct chemical entities with different chemical and physical properties.
5. STEREOISOMERISM
Same molecular formula and chemical structure but a different
configuration (i.e. different three dimensional spatial
arrangement of their atoms)
Two types:
1. Optical isomers
2. Geometrical isomers
6. OPTICAL ISOMERISM
Enantiomers: A pair of stereoisomers that are non- superimposable mirror
images of each other.
• presence of a chiral centre.
• Physiochemical properties ( solubility, melting and boiling point ionization
constant) are identical.
• Four different groups/atoms are attached at 4 corner of regular tetrahedron,
than the molecule is asymmetric and exist in 2 new forms
8. Diastereomers
• Stereoisomers that are not mirror images of each other and are not
enantiomeric.
• Physiochemical properties are different.
• Separation is easy
9. GEOMETRIC ISOMERS
Geometric Isomer - is as a result of free rotation impossibility of molecule parts around double-bonded
C=C.
1. Cis Isomers
2. Trans Isomers
10. DISCOVERY OF OPTICALACTIVITY
• In 1850, French Physicist Jean-Baptise Biot observed that solutions of some organic
compounds like sugar and camphor have the ability to rotate plane polarized light
• Up till then the basis of this phenomenon was not yet known
11. CHIRALITY
• “Chirality” is the property possessed by a molecule with such spatial arrangement of atoms that it cannot
superimpose on its mirror image. The object and mirror image pair of molecules has the same
constituents and structural formula.
• Chiral centre / asymmetric carbon – A carbon atom attached to four different substituents.
12.
13. Optical activity
With chiral compounds, the plane of the polarized light is rotated through an
angle . A compound that rotatespolarized light is said to be optically active
14. Racemic mixture:
• It is an equimolar mixture of both Enantiomers and is thus optically inactive.
• Most chiral drugs are administered as racemicmixtures
Optical isomers of Sulindac
15. Naming convention
Based on optical activity
• Compounds that rotate the plane of polarized light to the right (clockwise) are called
dextrorotary d(+)IUPAC convention
• Compounds that rotate the plane of polarized light to the left (counterclockwise) are
called levorotary. l(-)IUPAC convention
• Racemic mixture: d,l or +,-
16. Why is Stereochemistry and Chirality Important?
We’ve now learned the basics of stereochemistry - chirality, isomers, enantiomers, and optical
activity. Which leaves the question – why is this so important? And how does it relate to human
health?
• The simple answer was alluded to earlier in this report, which is - humans are chiral beings. From
the top or our heads to the tip of our toes practically every molecule in the human body is chiral , for
example, Receptors, enzymes, antibodies, and hormones.
• The enantiomers of a chiral drug may display different biological and pharmacological behaviors in
chiral living systems.
• Thereby creating a chiral environment in which all the body’s biochemical interactions take place.
This is important because the biochemical response to a particular molecule often depends on how
that molecule fits a particular site on a receptor molecule. As only the left-handed glove will fit the left
hand, so too will a left- handed receptor require a particular enantiomer (left-handed) for a correctfit.
17. This can be easily understood with the example of a drug-receptor model depicted in. In
possession of different spatial configurations, one active isomer may bind precisely to the
target sites (α, β, γ), while an inactive isomer may have an unfavorable binding or bind to
other unintended targets. Pharmacological effects of enantiomeric drugs may be
categorized as follows
18. Easson and Stedman model
L.H Easson and E. Steadman(1993)
hypothised that stereospecificity of optical
isomers in biological action is due to one
isomer being able to achieve a three point
attachment with its receptor molecule
19. • The point illustrated by adrenaline (with its nitrogen quaternised),the(-)isomer of
which is more active (with three Sites in contact with the receptor) than the (+)-
isomer which has only two point attachment with the same receptor due to change
in configuration at the β-carbon. It has been shown that deoxy-adrenaline which
lacks the alcoholic hydroxy group has about the same pressor effect as (+)-
adrenaline
20. Importanceofchiralityindrugs
• This stereoisomerism results in different physical and chemical properties of
the compound. If this compound happens to be drug then it results in different
pharmacokinetic and pharmacodynamic properties
• The importance of chiral drugs in the drug development space cannot be
understated. In pharmaceutical industries, 56% of the drugs currently in use
are chiral molecules and 88% of the last ones are marketed as racemates (or
racemic mixtures), consisting of an equimolar mixture of two enantiomers.
21. • In 1960 in Europe, racemic thalidomide was given to pregnant
females to cure morning sickness.
• This led to deformations in babies and neurotoxiceffects.
• These were due to S-thalidomide.
• R-thalidomide contained the desired therapeutic activity
Thalidomide-disastrous biological activity of the wrong
enantiomer
24. carvedilol sotalol
1. Both enantiomers act on the same biological target(s), but one isomer has
higher binding affinity than the other.
• For example, carvedilol is marketed as a racemate for the treatment of hypertension
and congestive heart failure. It is a nonselective β- and α-adrenergic receptor
blocking agent. Nonselective β blocking activity resides mainly in the (S )-carvedilol,
and the α-blocking effect is shared by both (R)- and (S )-enantiomers.
• Sotalol is a racemic β-adrenergic blocker. The (R)-enantiomer possesses the
majority of the β-blocking activity, and the (R)- and (S )- enantiomers of sotalol share
an equivalent degree of class III antiarrhythmic potency.
25. 2. Both enantiomers act on the same biological target, but exert opposed
pharmacological activities:
• For example, (–)-dobutamine demonstrated an agonistic activities against α-
adrenoceptors, whereas its antipode (+)- dobutamine is an antagonist against the
same receptors. The latter also acts as an β1-adrenoceptor agonist with a tenfold
higher potency than the (–) isomer and is used to treat cardiogenic shock.
• The individual enantiomers of the 1,4-dihydropyridine analog Bayk8644 have
opposing effects on L-type calcium channels, with the (S )-enantiomer being an
activator and the (R)-enantiomer an antagonist
(-)-dobutamine Bayk8644
26. 3. Both enantiomers may act similarly, but they do not have a synergistic effect:
• Two enantiomers of ∆-3-tetrahydrocannabinol (S)or(R) were assayed in humans for
psychoactivity. The 1S enantiomer had definite psychic actions, qualitatively similar to
those of ∆-1-tetrahydrocannabinol,but quantitatively less potent (1:3 to 1:6).
• Adding two enantiomers together did not increase the effect, confirming that activity was
solely in one enantiomer and that there was no synergistic effect between the two
isomers
∆-3-tetrahydrocannabinol (S) and (R)
27. 4. Both enantiomers have independent therapeutic effects through action on
different targets:
• The classical example of this behavior is quinine and quinidine. Quinine, which
was originally obtained from the bark of cinchona trees, has been used for the
treatment of malaria for centuries.
• Quinidine, on the other hand, is used as a class 1A antiarrhythmic agent and
acts by increasing action potential duration.
quinine and quinidine
28. 5. One or both enantiomers have the desired effect; at the same time, only
one enantiomer can cause unwanted side effects:
Racemic dropropizine has long been used in human therapy as an antitussive
agent. Recent studies have revealed that (S )-dropropizine possesses the same
antitussive activity as the racemic mixture, but has much lower selective activity on
the CNS. Therefore, particular clinical significance is attached to drugs of which
one enantiomer may contribute side or toxic effects
dropropizine
29. 6. The inactive enantiomer might antagonize the side effects of the active
antipode:
• In such cases, taking into account both efficacy and safety aspects, the racemate
seems to be superior to either enantiomer alone. For example, the opioid analgesic
tramadol is a used as a racemate and is not associated with the classical side
effects of opiate drugs, such as respiratory depression, constipation, or sedation.
• The (+)-enantiomer is a selective agonist for μ receptors with preferential inhibition
of serotonin reuptake and enhances serotonin efflux in the brain, whereas the (–)-
enantiomer mainly inhibits noradrenaline reuptake. The incidence of side effects,
particularly opioid-mediated effects, was higher with the (+)-enantiomer than with ±
tramadol or the (–)-enantiomer. Therefore, the racemate of tramadol is superior to
the enantiomers for the treatment of severe postoperative pain.
31. 7. One isomer is active and the other isomer is responsible for toxicity
• D-penicillamine(S) is an antiarthritic drug while enantiomer L-penicillamine (R) is
extremely toxic
• (S,S)-Ethambutol is an antitubercular while (R,R)-ethambutol has ocular toxicity
32. 8.The two isomer of the same molecule differ not only with respect to
pharmacological or biological activities but may differ in taste or colour
• (R)-Carvone has caraway odour while (S)-carvone has spearmint odour.
• D- and L-asparagine where the former has sweet taste while the latter has
tasteless.
35. 1.Etomidate
• Etomidate is a intravenous anaesthetic drug.
• Administered as a single isomer: R-isomer.
• Site of action: GABAa receptor.
• R-isomer is 15 times more potent than the S-isomer.
• S-isomer lacks hypnotic activity.
37. • S-ketamine is 2-4 times more potent than R-ketamine
• as an anaesthetic and analgesic agent.
R-ketamine: Emergence reactions like hallucinations, vivid dreams and agitation
• Ketamine is highly lipid soluble and acts rapidly
• The primary site of action of ketamine is in the cortex and subcortical areas
Ketamine acts mainly by inhibiting the NMDA type of excitatory amino acid
receptors in brain and not interacting with GABA A receptor
• Metabolism of S-ketamine by liver microsomes is 20% greater than R-ketamine
and 10% greater than the racemate - faster clearance of the drug.
38. 3.BUPIVACAINE
Long acting local anaesthetic marketed as 50:50 racemic mixture.
• Reports of death due to
• Bupivacaine induced CNS toxicity and cardiotoxicity on accidental
intravenous injection and
• Difficult resuscitation following cardiotoxicity.
Safer alternatives:
Levobupivacaine
The s(-) enantiomer of bupivacaine is equally potent but
less cardiotoxic and less prone to cause seizures than racemic bupivacaine.
It is being used as single enantiomer in some countries
39. Ropivacaine
• it act as local analgesic agent.
• r(+) and s(-) enantiomers of local anesthetics have been demonstrated to have
different affinity for different ion channels of sodium, potassium, and calcium.
• the s(-)enantiomer have low central nervous system (CNS) and cardiac toxicity
(cardiotoxicity) as compared with the r(+)enantiomer.
• ropivacaine causes reversible inhibition of sodium ion influx, and thereby blocks
impulse conduction in nerve fibers. this action is potentiated by dose-
dependent inhibition of potassium channels. ropivacaine is less lipophilic than
bupivacaine and is less likely to penetrate large myelinated motor fibers;
therefore, it has selective action on the pain-transmitting a β and c nerves
rather than aβ fibers, which are involved in motor function
40. 4. ISOFLURANE
• Some studies have found S(+)-isoflurane to be 50% more potent than R(-)-
isoflurane while other studies have found no significant difference.
• Both enantiomers are equally soluble in the lipid bilayers.
• S-isoflurane induced about 50% longer sleep times than R-isoflurane.
• Isoflurane likely binds to GABA, glutamate and glycine receptors, but
has different effects on each receptor
41.
42. 5.Atracurium
• Intermediate duration non-depolarizing neuromuscular blocker.
• Causes histamine release, transient hypotension, tachycardia, facial or
truncal flushing.
• Continuous infusion in critical patients can lead to laudanosine
accumulation, which is epileptogenic.
• Its structure contains 4 chiral centres and is a mixture of 10 optical and geometric
isomers.
43. Cis-atracurium
• It is R-R’ optical isomer representing 15% of the
mixture
• It is more safe
• Causes less histamine release
• Not been reported to cause bronchospasm
44. CETIRIZINE
• Cetirizine, an effective H1‐receptor antagonist, is a racemate mixture of two enantiomers:
levocetirizine (R enantiomer) and dextrocetirizine (S enantiomer)
• antihistaminic effects were not seen with dextrocetirizine
• Levocetirizine have less sedative effect than dextrocetirizine
45. WARFARINE
• Warfarin is administered as racemate.
• Warfarin (WAR) is widely used as an oral anticoagulant and functions as a vitamin K antagonist by
inhibiting the synthesis of vitamin K reductase and vitamin K epoxide reductase, thus decreasing
the ability of blood to form clot
• The (S)-WAR is 2–5 times more potent anticoagulant, and is metabolized much quicker (~1.5 times
faster) than the (R)-WAR
46. PENICILLIN
• The penicillin molecule contain three chiral carbon atoms at C-3, C-5 and C-6
• All natural and synthetic penicillin's have the same absolute configuration about these
three centres
• The 6th carbon atom bearing the acetyl amino group has the L-configuration, where as
the carbon to which the carboxyl group was attached has the D-configuration.
• Thus the acetyl amino group and carboxyl group are trans to each other, with the former
α and latter in the β orientation relative to penam ring.
• The absolute stereochemistry of the penicillin was designated as 3S:5R:6R.
• The atoms composing the 6- amino penicillanic acid are biosynthetically derived from
two amino acid , L-cysteine and D- valine
47. Isomer of ampicillin
D- isomer of ampicillin is 2-8 times more potent than l-isomer
• penicillin-v ampicillin
•