The classical approach for prodrug design uses the non-specific strategy of covalently modifying the drug of interest by attaching hydrophilic functionalities
This document discusses biological drug targets and summarizes key points about receptors and drug-receptor interactions. It begins with an introduction to biological drug targets and explains that drugs produce their effects by binding to receptors and causing biochemical or physical changes. It then discusses the main types of receptors - ligand-gated ion channels, G-protein coupled receptors, kinase-linked receptors, and nuclear receptors. Theories of drug-receptor interaction are also summarized, including occupancy theory, rate theory, induced fit theory, and others. Finally, the document briefly introduces artificial enzymes as synthetic molecules that can mimic the functions of natural enzymes.
Relationship between hansch analysis and free wilson analysisKomalJAIN122
This document provides an overview of quantitative structure-activity relationship (QSAR) modeling techniques including Hansch analysis, Free-Wilson analysis, and Topliss schemes. It discusses how QSAR relates the biological activity of drugs to their physicochemical properties through equations. Specifically, it explains that Hansch equations relate activity to hydrophobicity, electronic effects, and steric factors. Examples of Hansch equations are provided. The Free-Wilson approach derives equations based on the presence or absence of substituents. Topliss schemes provide a methodical approach to substituent selection for optimization.
This document summarizes the main types of biological drug targets: receptors. It discusses four main classes of receptors: 1) G-protein coupled receptors, which bind ligands and activate G-proteins to interact with ion channels or enzymes, 2) ligand gated ion channel receptors, which open channels to allow ion passage upon ligand binding, 3) enzyme linked receptors with intracellular enzyme domains that are activated by ligand binding to induce intracellular signaling cascades, and 4) nuclear receptors within cells that directly bind DNA to regulate gene expression in response to ligands such as steroid hormones.
This document provides an overview of prodrug design and practical considerations. It defines prodrugs as chemically inert precursors that release the active pharmacological compound. Prodrugs are classified based on their carrier and linker groups. The rationale for prodrug design includes improving solubility, enhancing membrane permeability, reducing pre-systemic metabolism, and targeting delivery to specific sites. Practical considerations for prodrug design involve the use of ester, amide, phosphate and carbamate groups to link the drug. The document discusses several examples of prodrugs and their advantages over parent drugs.
Drug resistance occurs through several mechanisms: mutation, selective pressure, and gene transfer allow microbes to develop resistance. Strategies to combat resistance include international collaboration on surveillance and incentives for new drugs, national treatment guidelines and education programs, and community efforts like rational antibiotic use and hygiene. Genetic changes allow microbes to develop resistance through various mechanisms like mutation, selective pressure, and horizontal gene transfer between microbes.
This presentation discusses drug target identification and validation. It introduces drug targets as specific sites where drugs bind to exert their therapeutic effects. Target identification methods include genomics, proteomics, and bioinformatics. Targets are then validated using techniques like siRNAs and antisense oligonucleotides to demonstrate the functional role of targets in disease and ensure drug interactions produce the desired therapeutic response.
This document summarizes several organic reactions used in heterocyclic chemistry. It describes the Debus–Radziszewski reaction for imidazole synthesis, the Knorr reaction for pyrrole synthesis, the Pinner reaction for pyrimidine synthesis, the Combes reaction for quinoline synthesis, the Bernthsen reaction for acridine synthesis, the Smiles rearrangement, and the Traube reaction for purine synthesis. For each reaction, it provides the starting materials, product, mechanism, and some applications. The document is intended to present an overview of important heterocyclic reactions for students of pharmaceutical chemistry.
Role of chirality in stereoselective and specific theraputic agentKaranvir Rajput
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.
This document discusses biological drug targets and summarizes key points about receptors and drug-receptor interactions. It begins with an introduction to biological drug targets and explains that drugs produce their effects by binding to receptors and causing biochemical or physical changes. It then discusses the main types of receptors - ligand-gated ion channels, G-protein coupled receptors, kinase-linked receptors, and nuclear receptors. Theories of drug-receptor interaction are also summarized, including occupancy theory, rate theory, induced fit theory, and others. Finally, the document briefly introduces artificial enzymes as synthetic molecules that can mimic the functions of natural enzymes.
Relationship between hansch analysis and free wilson analysisKomalJAIN122
This document provides an overview of quantitative structure-activity relationship (QSAR) modeling techniques including Hansch analysis, Free-Wilson analysis, and Topliss schemes. It discusses how QSAR relates the biological activity of drugs to their physicochemical properties through equations. Specifically, it explains that Hansch equations relate activity to hydrophobicity, electronic effects, and steric factors. Examples of Hansch equations are provided. The Free-Wilson approach derives equations based on the presence or absence of substituents. Topliss schemes provide a methodical approach to substituent selection for optimization.
This document summarizes the main types of biological drug targets: receptors. It discusses four main classes of receptors: 1) G-protein coupled receptors, which bind ligands and activate G-proteins to interact with ion channels or enzymes, 2) ligand gated ion channel receptors, which open channels to allow ion passage upon ligand binding, 3) enzyme linked receptors with intracellular enzyme domains that are activated by ligand binding to induce intracellular signaling cascades, and 4) nuclear receptors within cells that directly bind DNA to regulate gene expression in response to ligands such as steroid hormones.
This document provides an overview of prodrug design and practical considerations. It defines prodrugs as chemically inert precursors that release the active pharmacological compound. Prodrugs are classified based on their carrier and linker groups. The rationale for prodrug design includes improving solubility, enhancing membrane permeability, reducing pre-systemic metabolism, and targeting delivery to specific sites. Practical considerations for prodrug design involve the use of ester, amide, phosphate and carbamate groups to link the drug. The document discusses several examples of prodrugs and their advantages over parent drugs.
Drug resistance occurs through several mechanisms: mutation, selective pressure, and gene transfer allow microbes to develop resistance. Strategies to combat resistance include international collaboration on surveillance and incentives for new drugs, national treatment guidelines and education programs, and community efforts like rational antibiotic use and hygiene. Genetic changes allow microbes to develop resistance through various mechanisms like mutation, selective pressure, and horizontal gene transfer between microbes.
This presentation discusses drug target identification and validation. It introduces drug targets as specific sites where drugs bind to exert their therapeutic effects. Target identification methods include genomics, proteomics, and bioinformatics. Targets are then validated using techniques like siRNAs and antisense oligonucleotides to demonstrate the functional role of targets in disease and ensure drug interactions produce the desired therapeutic response.
This document summarizes several organic reactions used in heterocyclic chemistry. It describes the Debus–Radziszewski reaction for imidazole synthesis, the Knorr reaction for pyrrole synthesis, the Pinner reaction for pyrimidine synthesis, the Combes reaction for quinoline synthesis, the Bernthsen reaction for acridine synthesis, the Smiles rearrangement, and the Traube reaction for purine synthesis. For each reaction, it provides the starting materials, product, mechanism, and some applications. The document is intended to present an overview of important heterocyclic reactions for students of pharmaceutical chemistry.
Role of chirality in stereoselective and specific theraputic agentKaranvir Rajput
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.
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
Introduction
Classification
Therapeutic values of peptidomimetics
Design of peptidomimetics by manipulation of amino acids
Modification of peptide backbone
Chemistry of prostaglandins, leukotrienes and thromboxanes
This document provides an overview of prodrug design. It defines a prodrug as an inactive derivative of a drug molecule that undergoes biotransformation to release the active drug. Prodrugs are classified based on their structure and include carrier-linked, bipartite, tripartite, mutual, and bioprecursor prodrugs. The document discusses various rationales for prodrug design such as improving solubility, absorption, patient acceptability, and site-specific drug delivery. Common functional groups used in prodrugs include esters, amides, phosphates, and carbamates. The document also covers practical considerations and approaches for overcoming limitations like pre-systemic metabolism and blood-brain barrier penetration.
01.Rational Design of Enzyme inhibition.pptxPurushothamKN1
The document discusses rational design of enzyme inhibitors. It begins with an introduction to enzymes, including their protein nature and role in catalyzing biochemical reactions. It then covers enzyme kinetics and classifications of inhibitors. Reversible inhibitors include competitive inhibitors that resemble the substrate and non-competitive inhibitors that bind elsewhere. Irreversible inhibitors covalently bind the active site. The document emphasizes designing inhibitors through understanding enzyme structure and reaction mechanisms.
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
Oligonucleotide therapy involves using short strands of nucleic acids to alter gene expression and treat diseases. There are several techniques, including antisense oligonucleotides that bind to mRNA to inhibit translation, siRNA that induces mRNA degradation, and aptamers that bind to target proteins. Successful oligonucleotide therapy requires the oligonucleotide to be designed to target the desired gene, delivered to cells, accumulate intracellularly, and localize to active sites without compartmentalization to exert its activity. Major applications include oncology, cardiovascular and central nervous system disorders, and treating viruses, inflammation, and genetic diseases.
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.
This document discusses peptidomimetics, which are molecules that mimic peptides but do not contain peptide bonds. Peptidomimetics have increased bioavailability and duration of action compared to peptides. There are four types of peptidomimetics: Type I mimic peptide backbones, Type II are small molecules that bind peptide receptors, Type III have novel scaffolds that position essential groups, and Type IV are non-peptide molecules. Peptidomimetics have various therapeutic applications including antimicrobial, anticancer, antiviral, and antioxidant activities. They can be designed by replacing parts of peptides with non-peptide moieties or by hypothesizing the bioactive peptide form. Manipulating amino acids or their side chains allows creating
This document summarizes information about several antifungal drugs, including their molecular formulas, properties, synthesis methods, and uses. It discusses Ketoconazole, Terconazole, Metronidazole, and Miconazole. For each drug, it provides the molecular formula, describes the synthesis starting from various reactants and reaction steps, and lists clinical uses such as treating fungal infections, jock itch, and vaginal thrush. The document aims to provide information on the preparation and applications of important antifungal heterocyclic compounds.
This document discusses several reagents used in organic synthesis:
1) Wittig reagent is used to synthesize alkenes from ketones and aldehydes via the Wittig reaction. It is prepared from triphenylphosphine and alkyl halides.
2) Diazopropane is used for cyclopropanation of alkenes and is prepared by oxidation of acetohydrazone.
3) BOP reagent is commonly used for peptide coupling and esterification due to its ability to form reactive hydroxybenzotriazolyl intermediates. It involves generation of a carboxylate anion which attacks the phosphorus center.
In this slide I covered the detailed about hansch analysis, Free-Wilson analysis, and Mixed approach. I also gave a detailed application for each points.
The document discusses key concepts regarding enantiomers including:
1. Enantiomers are chiral molecules that are non-superimposable mirror images of one another that rotate plane-polarized light in opposite directions.
2. Diastereomers have more than one asymmetric carbon center and are physically different.
3. Differences in interactions between enantiomers and biological systems can lead to differences in pharmacological effects.
4. Stereoselectivity can occur during the absorption, distribution, metabolism, and excretion of chiral drugs due to interactions with transporters, proteins, and enzymes.
5. Case studies provide specific examples of how stereoselectivity influences the pharmacokinetics of drug enantiomers
Study of natural products as leads for new pharmaceuticalsRinshana Fathima
This document summarizes research on natural products as leads for cardiovascular drugs. It discusses how lovastatin, a fungal metabolite, was introduced in 1987 for treating hypercholesterolemia by inhibiting HMG-CoA reductase. The mechanism, isolation process, and structural features important for statin activity are described. Modifications to lovastatin led to the development of simvastatin, pravastatin, fluvastatin, cerivastatin, and atorvastatin, establishing the statin drug class for lowering cholesterol.
Global and local restrictions Peptidomimetics ASHOK GAUTAM
Peptidomimetics are small protein-like chains designed to mimic peptides but with greater stability and specificity. They are created either by modifying existing peptides or designing new structures that mimic peptides. Peptidomimetics incorporate conformational constraints locally or globally to restrict flexibility and exclude potential conformations, allowing for more targeted interaction with biological targets. Conformational constraints are needed to improve properties like stability, activity, and selectivity for applications like drug development and targeted cancer therapies. Common constraints include cyclization, disulfide bonds, and restricted amino acids.
This document discusses strategies for synthesizing three, four, five, and six-membered heterocyclic rings. It outlines three strategies for each ring size, including the Gabriel ring closure and Hassner synthesis for aziridines, pyrolysis of cyclopropyl azides and photocycloaddition for azetines, the Paal-Knorr and Hantzsch syntheses for pyrroles, and the Hantzsch synthesis and reactions with maleic anhydride for pyridines and pyridazines. A variety of heterocyclic compounds are derived from carbocyclic precursors by replacing carbon atoms with heteroatoms like nitrogen, oxygen, or sulfur.
The document discusses basic concepts and applications of prodrug design. It defines prodrugs as biologically inert derivatives of drug molecules that undergo enzymatic and/or chemical conversion in vivo to release the pharmacologically active parent drug. The objectives of prodrug design include improving pharmaceutical and pharmacokinetic properties as well as decreasing toxicity. Applications of prodrugs include masking taste/odor, reducing irritation, enhancing solubility/stability, improving bioavailability, preventing presystemic metabolism, prolonging duration of action, reducing toxicity, and enabling site-specific drug delivery such as in chemotherapy through directed enzyme prodrug therapy.
Prodrug strategy involves modifying drug molecules to improve their physicochemical or pharmacokinetic properties for better delivery. A prodrug is a biologically inactive derivative of a drug that is metabolized in the body to release the active drug molecule. Prodrugs can improve solubility, permeability, stability and reduce toxicity of a drug. Common prodrug modifications include esters, amides and bioprecursors. Prodrugs are designed to enhance bioavailability, prevent pre-systemic metabolism, prolong duration of action and enable site-specific drug delivery. Examples of prodrug applications include masking taste and odor, reducing injection site pain, and targeting anticancer drugs to tumor cells.
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
Introduction
Classification
Therapeutic values of peptidomimetics
Design of peptidomimetics by manipulation of amino acids
Modification of peptide backbone
Chemistry of prostaglandins, leukotrienes and thromboxanes
This document provides an overview of prodrug design. It defines a prodrug as an inactive derivative of a drug molecule that undergoes biotransformation to release the active drug. Prodrugs are classified based on their structure and include carrier-linked, bipartite, tripartite, mutual, and bioprecursor prodrugs. The document discusses various rationales for prodrug design such as improving solubility, absorption, patient acceptability, and site-specific drug delivery. Common functional groups used in prodrugs include esters, amides, phosphates, and carbamates. The document also covers practical considerations and approaches for overcoming limitations like pre-systemic metabolism and blood-brain barrier penetration.
01.Rational Design of Enzyme inhibition.pptxPurushothamKN1
The document discusses rational design of enzyme inhibitors. It begins with an introduction to enzymes, including their protein nature and role in catalyzing biochemical reactions. It then covers enzyme kinetics and classifications of inhibitors. Reversible inhibitors include competitive inhibitors that resemble the substrate and non-competitive inhibitors that bind elsewhere. Irreversible inhibitors covalently bind the active site. The document emphasizes designing inhibitors through understanding enzyme structure and reaction mechanisms.
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
Oligonucleotide therapy involves using short strands of nucleic acids to alter gene expression and treat diseases. There are several techniques, including antisense oligonucleotides that bind to mRNA to inhibit translation, siRNA that induces mRNA degradation, and aptamers that bind to target proteins. Successful oligonucleotide therapy requires the oligonucleotide to be designed to target the desired gene, delivered to cells, accumulate intracellularly, and localize to active sites without compartmentalization to exert its activity. Major applications include oncology, cardiovascular and central nervous system disorders, and treating viruses, inflammation, and genetic diseases.
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.
This document discusses peptidomimetics, which are molecules that mimic peptides but do not contain peptide bonds. Peptidomimetics have increased bioavailability and duration of action compared to peptides. There are four types of peptidomimetics: Type I mimic peptide backbones, Type II are small molecules that bind peptide receptors, Type III have novel scaffolds that position essential groups, and Type IV are non-peptide molecules. Peptidomimetics have various therapeutic applications including antimicrobial, anticancer, antiviral, and antioxidant activities. They can be designed by replacing parts of peptides with non-peptide moieties or by hypothesizing the bioactive peptide form. Manipulating amino acids or their side chains allows creating
This document summarizes information about several antifungal drugs, including their molecular formulas, properties, synthesis methods, and uses. It discusses Ketoconazole, Terconazole, Metronidazole, and Miconazole. For each drug, it provides the molecular formula, describes the synthesis starting from various reactants and reaction steps, and lists clinical uses such as treating fungal infections, jock itch, and vaginal thrush. The document aims to provide information on the preparation and applications of important antifungal heterocyclic compounds.
This document discusses several reagents used in organic synthesis:
1) Wittig reagent is used to synthesize alkenes from ketones and aldehydes via the Wittig reaction. It is prepared from triphenylphosphine and alkyl halides.
2) Diazopropane is used for cyclopropanation of alkenes and is prepared by oxidation of acetohydrazone.
3) BOP reagent is commonly used for peptide coupling and esterification due to its ability to form reactive hydroxybenzotriazolyl intermediates. It involves generation of a carboxylate anion which attacks the phosphorus center.
In this slide I covered the detailed about hansch analysis, Free-Wilson analysis, and Mixed approach. I also gave a detailed application for each points.
The document discusses key concepts regarding enantiomers including:
1. Enantiomers are chiral molecules that are non-superimposable mirror images of one another that rotate plane-polarized light in opposite directions.
2. Diastereomers have more than one asymmetric carbon center and are physically different.
3. Differences in interactions between enantiomers and biological systems can lead to differences in pharmacological effects.
4. Stereoselectivity can occur during the absorption, distribution, metabolism, and excretion of chiral drugs due to interactions with transporters, proteins, and enzymes.
5. Case studies provide specific examples of how stereoselectivity influences the pharmacokinetics of drug enantiomers
Study of natural products as leads for new pharmaceuticalsRinshana Fathima
This document summarizes research on natural products as leads for cardiovascular drugs. It discusses how lovastatin, a fungal metabolite, was introduced in 1987 for treating hypercholesterolemia by inhibiting HMG-CoA reductase. The mechanism, isolation process, and structural features important for statin activity are described. Modifications to lovastatin led to the development of simvastatin, pravastatin, fluvastatin, cerivastatin, and atorvastatin, establishing the statin drug class for lowering cholesterol.
Global and local restrictions Peptidomimetics ASHOK GAUTAM
Peptidomimetics are small protein-like chains designed to mimic peptides but with greater stability and specificity. They are created either by modifying existing peptides or designing new structures that mimic peptides. Peptidomimetics incorporate conformational constraints locally or globally to restrict flexibility and exclude potential conformations, allowing for more targeted interaction with biological targets. Conformational constraints are needed to improve properties like stability, activity, and selectivity for applications like drug development and targeted cancer therapies. Common constraints include cyclization, disulfide bonds, and restricted amino acids.
This document discusses strategies for synthesizing three, four, five, and six-membered heterocyclic rings. It outlines three strategies for each ring size, including the Gabriel ring closure and Hassner synthesis for aziridines, pyrolysis of cyclopropyl azides and photocycloaddition for azetines, the Paal-Knorr and Hantzsch syntheses for pyrroles, and the Hantzsch synthesis and reactions with maleic anhydride for pyridines and pyridazines. A variety of heterocyclic compounds are derived from carbocyclic precursors by replacing carbon atoms with heteroatoms like nitrogen, oxygen, or sulfur.
The document discusses basic concepts and applications of prodrug design. It defines prodrugs as biologically inert derivatives of drug molecules that undergo enzymatic and/or chemical conversion in vivo to release the pharmacologically active parent drug. The objectives of prodrug design include improving pharmaceutical and pharmacokinetic properties as well as decreasing toxicity. Applications of prodrugs include masking taste/odor, reducing irritation, enhancing solubility/stability, improving bioavailability, preventing presystemic metabolism, prolonging duration of action, reducing toxicity, and enabling site-specific drug delivery such as in chemotherapy through directed enzyme prodrug therapy.
Prodrug strategy involves modifying drug molecules to improve their physicochemical or pharmacokinetic properties for better delivery. A prodrug is a biologically inactive derivative of a drug that is metabolized in the body to release the active drug molecule. Prodrugs can improve solubility, permeability, stability and reduce toxicity of a drug. Common prodrug modifications include esters, amides and bioprecursors. Prodrugs are designed to enhance bioavailability, prevent pre-systemic metabolism, prolong duration of action and enable site-specific drug delivery. Examples of prodrug applications include masking taste and odor, reducing injection site pain, and targeting anticancer drugs to tumor cells.
The document discusses pro-drugs, which are inactive precursors designed to improve the delivery of active drug molecules. It describes how pro-drugs can be used to mask tastes/odors, modify formulations, enhance solubility, reduce side effects like GI irritation, and target drug delivery. Pro-drugs are metabolized in the body to release the active drug. Types include carrier-linked prodrugs, bioprecursor prodrugs, and mutual prodrugs, which release two active drugs. Applications include taste masking, solubility enhancement, and site-specific delivery to improve drug therapies.
The document discusses the concept of prodrugs. It defines prodrugs as therapeutically inactive compounds that are metabolized into active drug metabolites. The objectives of prodrug design are to overcome barriers like poor solubility, stability, absorption and toxicity. An ideal prodrug is pharmacologically inert, transforms rapidly into the active form at the target site, and produces non-toxic metabolic fragments. Prodrugs are classified based on their structure and site of conversion. The applications of prodrugs include improving drug properties and delivery.
The document discusses prodrug design and its applications. Prodrugs are biologically inert derivatives of drug molecules that undergo conversion in vivo to release the active parent drug. The objectives of prodrug design are to improve pharmaceutical and pharmacokinetic properties like solubility, stability, absorption and bioavailability. Prodrugs can be classified based on the carrier group attached and site of bioactivation. Applications include masking taste/odor, reducing irritation, enhancing solubility, stability and bioavailability to improve drug delivery. In summary, prodrug design is a strategy to overcome undesirable drug properties and improve therapeutic effectiveness.
This document provides an overview of prodrug design. It defines a prodrug as an inert derivative of a drug molecule that undergoes biotransformation to release the active parent drug. Prodrugs can be classified based on their structure and include carrier-linked, bipartite, tripartite, mutual, and bioprecursor prodrugs. The rationale for prodrug design includes improving solubility, absorption, bioavailability, site-specific delivery, and overcoming issues like poor stability, toxicity and patient acceptability. Practical considerations for developing prodrugs with esters, amides, phosphates and carbamates are discussed. The document outlines various approaches of prodrug design to optimize the pharmacokinetic and pharmac
The document discusses prodrugs, which are inactive compounds that are metabolized into active drug metabolites. It provides background on the history of prodrugs, the prodrug concept, objectives of prodrug design, properties of ideal prodrugs, classifications of prodrugs, and limitations and applications of prodrugs. Specifically, it describes how prodrugs can overcome barriers like poor solubility, stability issues, low absorption, and toxicity to improve drug delivery and pharmacokinetics. Prodrugs are classified based on their structure and site of conversion to the active drug. Common examples of early prodrugs included aspirin and chloramphenicol derivatives.
Prodrugs are inactive derivatives of active drug molecules that undergo biotransformation in the body to release the active drug. They are designed to improve drug solubility, stability, absorption, distribution, and reduce toxicity and side effects. Prodrugs can be classified as carrier-linked or bioprecursor types. The carrier-linked type attaches the active drug to an inert carrier molecule through a metabolically labile bond. Bioprecursor prodrugs rely on metabolic activation like oxidation or phosphorylation to release the active drug. Key steps in prodrug design involve identifying delivery problems and selecting a carrier to impart the desired properties while releasing the active drug in the target area. Common applications of prodrugs include targeting the brain
Basic concepts of Prodrug & their application in pharmacy fieldsSHUVAM SAR
Definition of prodrugs along with their uses in pharmacy have been discusses here in brief. Also includes the basic objectives of their formulation with examples.
Understanding the role of pharmacology in prosthodontics is imperative because this is one of the most neglected parts of research even though there are a large number of dental patients suffering from systemic diseases which have to be taken care of before the commencement of dental treatment.
Another main reason is that the prosthodontist may have to deal with a medical emergency arising on the dental chair.
The document discusses macrolide antibiotics such as erythromycin, clarithromycin, and azithromycin. It also discusses the antimalarial chloroquine and its mechanism of action, inhibiting heme polymerization in plasmodium parasites. The prodrug concept and applications are explained, including improving drug properties like taste, solubility, and bioavailability.
An excipient is generally a pharmacologically inactive substance used as a carrier for the active ingredients of a medication
EXCIPIENTS USED IN LIQUID DOSAGE FORMS:
Solvents/co-solvents ,
Buffering agents,
Preservatives,
Anti-oxidants,
Humectants,
Wetting agents,
Anti-foaming agents,
Thickening agents,
Sweetening agents,
Flavouring agents,
EXCIPIENTS USED IN TABLETS:
Binders
Coatings
Disintegrants
Fillers
Flavours
Colours
Lubricants
Glidants
Preservatives
Sweeteners
The document discusses the concept of prodrugs. It defines a prodrug as a pharmacologically inactive compound that is metabolized into an active drug. The goals of prodrug design include overcoming problems like instability, poor solubility, toxicity and inadequate absorption. Ideal prodrugs are metabolized into active drugs at the target site and have non-toxic carrier molecules. Prodrugs can improve properties like solubility, lipophilicity, targeting, and duration of action to optimize drug delivery. Examples provided are valacyclovir, famciclovir and capecitabine.
The document discusses prodrugs, which are chemically modified inactive precursors of drug molecules that are converted in vivo to release the active drug. Prodrugs can improve pharmaceutical and pharmacokinetic properties like solubility, stability, absorption and bioavailability. They are classified based on the attachment of an inert carrier group (carrier-linked), the presence of two moieties (bipartite), a linker between drug and carrier (tripartite), or two active drugs coupled together (mutual). Prodrugs aim to overcome issues like poor solubility, taste, irritation and increase absorption for improved drug delivery.
The document discusses prodrugs, which are pharmacologically inactive derivatives of active drugs designed to improve drug properties like solubility, absorption, and site-specific delivery. It covers basic prodrug concepts and classifications like carrier-linked prodrugs and bioprecursors. Approaches for prodrug design include using carriers, linkers, and multi-drug systems. Applications of prodrugs include improving patient acceptability by modifying taste, odor or irritation, enhancing solubility and dissolution for better absorption, and enabling site-specific or sustained drug delivery. The document provides examples of prodrug linkages and enzymes involved in their hydrolysis.
Prodrug basic concepts and application of Prodrug Design.pptxpankajnepal764
This document discusses prodrugs, which are inactive precursors to pharmacologically active drugs. Prodrugs are designed to improve drug properties like solubility, stability, taste, and bioavailability. Prodrugs undergo biotransformation in the body to release the active drug. They are classified as carrier-linked or bioprecursors based on their structure and activation method. Common applications of prodrugs include improving taste and odor, enhancing bioavailability, increasing stability and solubility, reducing toxicity, and allowing site-specific drug delivery. Prodrugs can also prolong the duration of drug action.
A prodrug is an inactive pharmacological compound that is metabolized into an active drug within the body. Prodrugs improve drug properties like membrane permeability, absorption, distribution, solubility, metabolism, toxicity and elimination. Common prodrug types include carrier-linked prodrugs where an active drug is linked to a carrier group that is enzymatically removed, and bioprecursors that are metabolized into the active drug. Prodrugs can prolong a drug's duration of action by slowing its release and conversion into the active form in tissues and blood. While prodrugs provide benefits like reduced toxicity and improved drug delivery, their design must avoid forming unexpected toxic metabolites during activation.
Pharmacosomes are lipid-based vesicular drug delivery systems where drugs are covalently bound to lipids. They can incorporate both hydrophilic and lipophilic drugs and deliver them in a targeted manner. Pharmacosomes have advantages like high drug loading, direct delivery to the site of action, and reduced toxicity. They are formulated using techniques like solvent evaporation, ether injection, and lyophilization. Pharmacosomes show potential for improving drug absorption, transport, and therapeutic effects. Evaluation methods include assessing solubility, drug content, surface morphology, thermal behavior, and in vitro drug release.
Computer-aided design (CAD) is the use of computers (or workstations) to aid in the creation, modification, analysis, or optimization of a design: 3 This software is used to increase the productivity of the designer, improve the quality of design, improve communications through documentation, and to create a database for manufacturing: 4 Designs made through CAD software are helpful in protecting products and inventions when used in patent applications. CAD output is often in the form of electronic files for print, machining, or other manufacturing operations. The terms computer-aided drafting (CAD) and computer-aided design and drafting (CADD) are also used
Acute respiratory infection (ARI) is an infection that interferes with normal breathing by affecting the upper or lower respiratory tract. Common causative organisms include rhinoviruses, respiratory syncytial virus, influenza virus, and parainfluenza virus. Symptoms include congestion, runny nose, cough, sore throat, body aches, and fatigue. ARIs are transmitted through airborne droplets from coughing or sneezing. Prevention methods include breastfeeding, avoiding indoor air pollution, and immunizing against measles, HIB, pneumococcal disease, and other pathogens. WHO is working to improve diagnosis and management of ARIs.
Acute respiratory infections (ARIs) are classified as upper respiratory tract infections (URIs) or lower respiratory tract infections (LRIs). The upper respiratory tract consists of the airways from the nostrils to the vocal cords in the larynx, including the paranasal sinuses and the middle ear.
CALIBRATION PROTOCOL AS PER USFDA GUIDELINES.pptxManimegalaiG3
A calibration procedure is a controlled document that provides a validated method for evaluating and verifying the essential performance characteristics, specifications, or tolerances for a model of measuring or testing equipment.
ICH guidelines are a set of guidances to ensure safe, effective and high-quality medicines are developed and registered efficiently. These guidelines have been adopted by regulatory authorities throughout the world.
Nucleophilic substitution reactions are a class of reactions in which an electron rich nucleophile attacks a positively charged electrophile to replace a leaving group. For alginate reactions, the most reactive nucleophile is the C6 carboxylate group
The document discusses protecting groups for amino groups and amino acids. It first introduces the concept of protecting groups by explaining that they make it possible to selectively react a less reactive functional group in the presence of a more reactive group. It notes that protecting groups block reactivity by converting the functional group to an inert form. The document then lists desirable qualities for choosing a suitable protecting group, including being cheap, stable to reaction conditions, and easy to remove. It proceeds to discuss carbamate and amide protecting groups specifically for amino groups.
NMR Spectroscopy is abbreviated as Nuclear Magnetic Resonance spectroscopy. Nuclear magnetic resonance (NMR) spectroscopy is the study of molecules by recording the interaction of radiofrequency (Rf) electromagnetic radiations with the nuclei of molecules placed in a strong magnetic field.
Infrared (IR) spectroscopy is an absorption method widely used in both qualitative and quantitative analyses. The infrared region of the spectrum includes electromagnetic radiation that can alter the vibrational and rotational states of covalent bonds in organic molecules.The IR spectrum of an organic compound is a unique physical property and can be used to identify unknowns by interpretation of characteristic absorbances and comparison with spectral libraries. IR spectroscopy is also used in quantitative techniques because of its sensitivity and selectivity. It can be used to quantitate analytes in complex mixtures and is used extensively in detection of industrial pollutants in the environment.
How to Add Chatter in the odoo 17 ERP ModuleCeline George
In Odoo, the chatter is like a chat tool that helps you work together on records. You can leave notes and track things, making it easier to talk with your team and partners. Inside chatter, all communication history, activity, and changes will be displayed.
A Strategic Approach: GenAI in EducationPeter 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.
Assessment and Planning in Educational technology.pptxKavitha Krishnan
In an education system, it is understood that assessment is only for the students, but on the other hand, the Assessment of teachers is also an important aspect of the education system that ensures teachers are providing high-quality instruction to students. The assessment process can be used to provide feedback and support for professional development, to inform decisions about teacher retention or promotion, or to evaluate teacher effectiveness for accountability purposes.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
বাংলাদেশের অর্থনৈতিক সমীক্ষা ২০২৪ [Bangladesh Economic Review 2024 Bangla.pdf] কম্পিউটার , ট্যাব ও স্মার্ট ফোন ভার্সন সহ সম্পূর্ণ বাংলা ই-বুক বা pdf বই " সুচিপত্র ...বুকমার্ক মেনু 🔖 ও হাইপার লিংক মেনু 📝👆 যুক্ত ..
আমাদের সবার জন্য খুব খুব গুরুত্বপূর্ণ একটি বই ..বিসিএস, ব্যাংক, ইউনিভার্সিটি ভর্তি ও যে কোন প্রতিযোগিতা মূলক পরীক্ষার জন্য এর খুব ইম্পরট্যান্ট একটি বিষয় ...তাছাড়া বাংলাদেশের সাম্প্রতিক যে কোন ডাটা বা তথ্য এই বইতে পাবেন ...
তাই একজন নাগরিক হিসাবে এই তথ্য গুলো আপনার জানা প্রয়োজন ...।
বিসিএস ও ব্যাংক এর লিখিত পরীক্ষা ...+এছাড়া মাধ্যমিক ও উচ্চমাধ্যমিকের স্টুডেন্টদের জন্য অনেক কাজে আসবে ...
A workshop hosted by the South African Journal of Science aimed at postgraduate students and early career researchers with little or no experience in writing and publishing journal articles.
How to Fix the Import Error in the Odoo 17Celine George
An import error occurs when a program fails to import a module or library, disrupting its execution. In languages like Python, this issue arises when the specified module cannot be found or accessed, hindering the program's functionality. Resolving import errors is crucial for maintaining smooth software operation and uninterrupted development processes.
Thinking of getting a dog? Be aware that breeds like Pit Bulls, Rottweilers, and German Shepherds can be loyal and dangerous. Proper training and socialization are crucial to preventing aggressive behaviors. Ensure safety by understanding their needs and always supervising interactions. Stay safe, and enjoy your furry friends!
This presentation was provided by Steph Pollock of The American Psychological Association’s Journals Program, and Damita Snow, of The American Society of Civil Engineers (ASCE), for the initial session of NISO's 2024 Training Series "DEIA in the Scholarly Landscape." Session One: 'Setting Expectations: a DEIA Primer,' was held June 6, 2024.
Physiology and chemistry of skin and pigmentation, hairs, scalp, lips and nail, Cleansing cream, Lotions, Face powders, Face packs, Lipsticks, Bath products, soaps and baby product,
Preparation and standardization of the following : Tonic, Bleaches, Dentifrices and Mouth washes & Tooth Pastes, Cosmetics for Nails.
it describes the bony anatomy including the femoral head , acetabulum, labrum . also discusses the capsule , ligaments . muscle that act on the hip joint and the range of motion are outlined. factors affecting hip joint stability and weight transmission through the joint are summarized.
This presentation includes basic of PCOS their pathology and treatment and also Ayurveda correlation of PCOS and Ayurvedic line of treatment mentioned in classics.
2. INTRODUCTION
• A Prodrug is pharmacologically inactive compound that is converted into
active drug by a metabolic biotransformation .
• Prodrug enhanced the usefulness of various therapeutic agents by altering
the physicochemical properties, pharmacokinetics and biopharmaceutical
properties.
• It might alter the tissue distribution , efficacy and toxicity of parent drug.
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4. REASONS FOR PRODRUG APPROACH
• Improved aqueous solubility
• Improved absorption and distribution
• Site specificity
• Improved stability of drugs
• For prolonged release
• To reduce toxicity
• In poor patient acceptability
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5. BASIC CONCEPT
• Prodrugs are pharmacologically inactive derivatives of active drugs that
are design to maximize the amount of active drug that reaches its site of
action, through manipulation of physicochemical , biopharmaceutical
and pharmacokinetic properties of drug.
• They are converted into active drug within the body through enzymatic
or non-enzymatic reaction.
Promoiety-Drug
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6. CARRIER LINKED PRODRUGS
• It is a complex that comprises an active drug which is temporarily
attached to some carrier with covalent linkage the carrier group can be
detached enzymatically.
• After administration to the body, the prodrug undergoes
biotransformation and converted to active compound.
a) Bipartite prodrug
b)Tripartite prodrug
c) Mutual prodrug
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7. BIPARTITE PRODRUG
• It is a prodrug composed of one carrier attached to the drug.( Drug+
Carrier)
• These are greatly modified lipophilicity due to the attached carrier . The
active released by hydrolytic cleavage either chemically or enzymatically.
For eg., Tolmetin – glycine prodrug (NSAIDs)
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8. TRIPARTITE PRODRUG
• In a tripartite prodrug, the carrier is not connected directly to the drug,
but rather to a linker which is attached to the drug.
• This allows for different kinds of functional to be incorporated for varying
stabilities and it also displaces the drug farther from the hydrolysis site,
which decrease the steric interference by the carrier.
• The drug – linker connection however, must be designed so that it cleaves
spontaneously after the carrier has been detached.
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10. MUTUAL PRODRUGS
• It consist of two pharmacologically active agents coupled together so that
each act as a promoiety for the other agent.
• It is a bipartite or tripartite prodrug in which the carrier is a synergistic
drug with the drug to which it is needed.
For eg., Benorilate (Mutual prodrug of aspirin and paracetamol)
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11. BIOPRECURSORS PRODRUG
• Bioprecursors results from the molecular modifications of the compound.
• There is no need of promoiety in bioprecursors. Carrier linked podrugs
rely largely hydrolysis reaction for their effectiveness, whereas
Bioprecursors prodrugs mostly utilize their oxidative or reductive
activation reaction.
a) Reductive Bioactivation
b)Oxidative activation
c) Oxidative deamination
d)N-oxidation
e) Azo reductive activation
f) Sulfoxide reduction
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12. REDUCTIVE BIOACTIVATION
• Omeprazole , effectively inhibits gastric secretion by inhibiting the gastric
H+ K+ ATPase. This enzyme is responsible for gastric acid secretion and
located in the secretory membranes of parietal cells.
• Invivo Omeprazole is transformed into the active inhibitor, a cyclic
sulfonamide, which forms disulfide bridge with thiol group of the enzyme
and thus inactivates enzyme
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14. OXIDATIVE ACTIVATION
• Bioprecursor prodrug is activated by O-dealkylation is the analgesic and
antipyretic agents Phenacetin , which is activity to its conversion by O-
dealkylation metabolism to Acetaminophen.
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15. OXIDATIVE DEAMINATION
• Cyclophosphamide is an alkylating agent it needs oxidative deamination
for active metabolite.
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16. N- OXIDATION
• Pralidoxime is an antidote for poisoning by organophosphorus
compound which is believed to be activated by N- oxidation.
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17. AZO REDUCTIVE ACTIVATION
• Sulfasalazine used in the treatment of inflammatory bowel disease is
reductively cleaved by anaerobic bacteria in the lower bowel to 5- amino
salicylic acid and sulfapyridine.
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18. SULFOXIDE REDUCTION
• The antiarthritis drug sulindac is an indene isostere of the drug
Indomethacin. Invivo it undergoes sulfoxide reduction to form an active
metabolite sulindac sulfide.
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19. PRODRUGS OF FUNCTIONAL GROUP
CARBOXYLIC ACID AND ALCOHOL
• Prodrugs of carboxylic acid & alcohol functionalities can be prepared
by conversion to esters. The esters can be easily hydrolysed by
esterase enzymes present in plasma and other tissues to give active
drug.
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20. AMINES
• Due to the high stability and lack of amidase enzyme necessary for
hydrolysis, the conversion of amines to amide as a prodrug is not been
used for most of the drugs.
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21. AZO LINKAGE
• Prodrugs of amines are occasionally prepared by incorporating them into
an azo linkage. By the action of azo reductase the amino compounds are
released.
For eg.,
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22. CARBONYL GROUP
For eg., Hexamine releases Formaldehyde in the Urine(acidic pH) which act
as an antibacterial agent.
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23. PRODRUGS TO IMPROVE PATIENT
ACCEPTABILITY
• Painful injections and unpleasant taste or odour are the most common
reasons for the lack of patient acceptance of a drug.
For eg., Ethyl Mercaptan is a foul smelling liquid used in the treatment of
leprosy. This is converted to phthalate ester, a diethyl dithioisophthalate that
has higher boiling point and is odourless.
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24. PRODRUG FOR IMPROVED ABSORPTION AND
DISTRIBUTION
• The skin is designed to maintain the body fluids and prevent absorption
of xenobiotics into the general circulation. Consequently , drugs applied
to the skin are poorly absorbed.
• Even steroids have low dermal permeability if they contain OH groups
that can interact with the skin or binding site in the keratin.
• Corticosteroids for the topical treatment of inflammatory , allergic and
pruritis skin conditions can be made more suitable for topical absorption
by esterification.
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25. • Fluocinonide is a prodrug of Flucinolone acetonide used for inflammtory
and pruritic manifestation . Once absorbed through the skin an esterase
release the drug.
Fluocinolone acetonide R =H (active)
Fluocinonide R= COCH3 (prodrug)
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26. PRODRUG FOR SITE SPECIFICITY
• Blood Brain Barrier a unique lipid like protective barrier that prevents
hydrophilic compounds from entering the brain unless they are actively
transported.
• An increasing the brain concentration of the inhibitory neurotransmitter
GABA results in anticonvulsant activity.
• However, GABA is too polar to cross the BBB so it is not an effective
anticonvulsant drug.
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27. • Progabide is an effective lipophilic analog of GABA that crosses the BBB,
releases GABA inside the brain and exhibit anticonvulsant activity.
GABA (unable to cross BBB)
Progabide (prodrug)
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28. PRODRUG FOR PROLONG ACTIVITY
• The prodrug by its improved characteristics get closer to the receptor site
for a longer period of time and conversion to the parent drug takes place
at the site of action.
• It reduces the number and frequency of dose
• It eliminates night time administration of drugs
• Minimize patient non compliance.
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29. • Haloperidol is a potent tranquilizer and its peak plasma observed
between 2-6 hrs after administration .The ester prodrug haloperidol
decanoate is injected i.m. as a solution in sesame oil and its antipsychotic
activity last for about 1 month.
Haloperidol decanoate (prodrug) Haloperidol (active)
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30. DRUG SOLUBILITY
• Hydrophilic or water soluble drugs are needed when parenteral or
ophthalmic formulation .
• Drug with hydroxyl functional group can be converted to their
hydrophilic form through the use of half ester such as hemi- glutarate or
hemi phthalate , the other half of this acid carries sodium, potassium or
amine salts and render this moiety more soluble.
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31. methyl prednisolone methyl presdnisolone
succinate ester
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32. RATIONALE OF PRODRUG DESIGN
• The prodrug design includes an infixed position that can be altered to improve
in membrane permeability, solubility and ADME properties.
• Different prodrugs used for cancer therapies and other related therapies
include,
• Antibody directed enzyme prodrug therapy
• Gene directed enzyme prodrug therapy
• Polymer directed enzyme prodrug therapy
• Virus directed enzyme prodrug therapy
• Lectin directed enzyme prodrug therapy
• Clostridiol directed enzyme prodrug therapy
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33. • ANTIBODY DIRECTED ENZYME PRODRUG THERAPY
In the targeted therapy , the antibody enzyme conjugate will help in
selective binding of enzyme to the tumor cell and then the prodrug
converts into the active drug by the targeted enzyme , thus only affecting
the tumor and leaving back the normal cells.
• GENE DIRECTED ENZYME PRODRUG THERAPY
It is a suicide gene therapy in which the enzyme required for prodrug
conversion is produced within the target cell , using a gene delivered to it
by gene therapy
• VIRUS DIRECTED ENZYME PRODRUG THERAPY
It is an emerging strategy against cancer to the use of virus . It can be
potentially used to enhance the therapeutic potential of oncolytic virus.
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34. • POLYMER DIRECTED ENZYME ACTIVATED PRODRUG
THERAPY
It is a novel two step antitumor approach using a combination of a
polymeric prodrug and polymeric enzyme conjugated to generate cytotoxic
drug selectivey at the tumor site.
• LECTIN DIRECTED ENZYME ACTIVATED PRODRUG
THERAPY
It is designed to exploit endogenous carbohydrate - lectin binding by
combining it with biocatalysis through the construction of novel
glycosylated enzymes and prodrugs.
• CLOSTRIDIA - DIRECTED ENZYME PRODRUG
THERAPY
The use of clostridia to convert prodrugs into active drug agents. It
expoits the tumor using anaerobic bacteria resident in the tumor to convert
the prodrug to the active form
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