Drug discovery and development is a multi-step process that begins with identifying a disease target and ends with marketing an approved drug. Key steps include finding a lead compound through screening libraries or natural sources, optimizing the lead through structure-activity relationships to improve potency and safety, and conducting preclinical and clinical trials to prove a drug's efficacy and safety in humans. The overall goal is to take a biologically active lead and design analogs with improved target binding, pharmacokinetic properties, toxicity profile, and manufacturability.
THE PRODRUG DESIGNING FOR NEW SELECTION AND FORMULATION OF DRUG COMPATIBLE WITH API I.E. ACTIVE PHARMACUTICAL INGREDIENT, AND ITS EFFECT WHICH SHOULD BE 0. THE DRUG COMBINED WITH API AND AVILABLE IN MARKET AND DRUGS NEED TO BE COMBINE ARE ALSO DISCUSSED WITH ITS STRUCTURE AND SAR, AND COVERED AS PER THE SYLLABUS OF PCI.
THE PRODRUG DESIGNING FOR NEW SELECTION AND FORMULATION OF DRUG COMPATIBLE WITH API I.E. ACTIVE PHARMACUTICAL INGREDIENT, AND ITS EFFECT WHICH SHOULD BE 0. THE DRUG COMBINED WITH API AND AVILABLE IN MARKET AND DRUGS NEED TO BE COMBINE ARE ALSO DISCUSSED WITH ITS STRUCTURE AND SAR, AND COVERED AS PER THE SYLLABUS OF PCI.
THE DRUG DESIGN AND DEVELOPMENT BASED ON DRUG DISCOVERY ,HERE ITS NEED RATIONALE ARE EXPLAINED ALSO QSAR, MOLECULAR DOCKING ITS HISTORY NEED, STRUCTURE BASED DRUG DESIGN IN EASY WAY WE HAVE MENTIONED. THIS WILL MAKE READERS EASY TO COLLECT DATA AT A PLACE ALL OVER THIS IS FOR PHARMA STUDENTS, ACADEMICS, PROFESSIONL AND OST USEFUL FOR RESEARCHERS.
THANK YOU
HOPE YOU WILL LIKE AND SHARE
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.
DRUG DISCOVERY
Drug Discovery without a lead
LEAD DISCOVERY/IDENTIFICATION
LEAD MODIFICATION
CONCEPT OF PRODRUGS AND SOFT DRUGS
DRUG RECEPTOR INTERACTIONS
ADMET properties prediction using AI will accelerate the process of drug discovery.
This slide mostly focuses on using graph-based deep learning techniques to predict drug properties.
PRESENTED BY: HARSHPAL SINGH WAHI, SHIKHA D. POPALI
USEFUL FOR PHARMACY STUDENTS AND ACADEMICS, INDUSTRIALS FOR MOLECULE DEVELOPMENT, MODELING, DRUG DISCOVERY, COMPUTATIONAL TOOLS, MOLECULAR DOCKING ITS TYPES, FACTORS AFFECTING, DIFFERENT STAGES, QSAR ADVANTAGES, NEED
THE DRUG DESIGN AND DEVELOPMENT BASED ON DRUG DISCOVERY ,HERE ITS NEED RATIONALE ARE EXPLAINED ALSO QSAR, MOLECULAR DOCKING ITS HISTORY NEED, STRUCTURE BASED DRUG DESIGN IN EASY WAY WE HAVE MENTIONED. THIS WILL MAKE READERS EASY TO COLLECT DATA AT A PLACE ALL OVER THIS IS FOR PHARMA STUDENTS, ACADEMICS, PROFESSIONL AND OST USEFUL FOR RESEARCHERS.
THANK YOU
HOPE YOU WILL LIKE AND SHARE
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.
DRUG DISCOVERY
Drug Discovery without a lead
LEAD DISCOVERY/IDENTIFICATION
LEAD MODIFICATION
CONCEPT OF PRODRUGS AND SOFT DRUGS
DRUG RECEPTOR INTERACTIONS
ADMET properties prediction using AI will accelerate the process of drug discovery.
This slide mostly focuses on using graph-based deep learning techniques to predict drug properties.
PRESENTED BY: HARSHPAL SINGH WAHI, SHIKHA D. POPALI
USEFUL FOR PHARMACY STUDENTS AND ACADEMICS, INDUSTRIALS FOR MOLECULE DEVELOPMENT, MODELING, DRUG DISCOVERY, COMPUTATIONAL TOOLS, MOLECULAR DOCKING ITS TYPES, FACTORS AFFECTING, DIFFERENT STAGES, QSAR ADVANTAGES, NEED
Target identification, target validation, lead identification and lead
Optimization.
• Economics of drug discovery.
• Target Discovery and validation-Role of Genomics, Proteomics and
Bioinformatics.
• Role of Nucleic acid microarrays, Protein microarrays, Antisense
technologies, siRNAs, antisense oligonucleotides, Zinc finger proteins.
• Role of transgenic animals in target validation.
DRUG DISCOVERY & DEVELOPMENT PROCESS, it's a detail description about how drug is made available in market it's development and discovery of drug The Hole Study is given in This Topic.
Modern drug discovery process|| M pharm Pharmacology.pptxRohit chaurpagar
Modern drug discovery is a complex, multidisciplinary process that involves several stages and utilizes advanced technologies. The goal is to develop new therapeutic agents that can safely and effectively treat diseases. Here’s an overview of the key stages in the modern drug discovery process
Introduction to Research Work, Experimental Tools and Data Processings.pptxResearchsio
Introduction to Research Work, Experimental Tools, and Data Processings was a topic of a workshop conveyed by Dr. Proshanta Roy, (University of Camerino) for the members of Researchsio. In the workshop, members learn about the basic steps of conducting a research work, the tools to help them in their works and managing the basic data of their project. Researchsio has always been concerned about maintaining a standard pro
Competition genomic medicine presentationResearchsio
Prepared By Roman Sharkar and Mir Tasfiq Alam. Both of them are students of the B.Pharm Program in Bangladesh. They prepared this ppt file from their choice of interest which is Genomic Medicine. Hope this will handly to the others who are interested in this topic !!
Researchsio your dream needs your help (higher stduy abroad)Researchsio
Prepared by Saqline Mostaq, (Trainer, Researchsio
Ex-Patient Support Executive, Roche Bangladesh limited.pharm, University of Asia Pacific) who is currently studying at the University of Grenoble Alpes, France providing the basic concept of the relation between Presentation and Research.
Relationship between Presentation and ResearchResearchsio
Prepared by Saqline Mostaq, (Trainer, Researchsio
Ex-Patient Support Executive, Roche Bangladesh limited.pharm, University of Asia Pacific) who is currently studying at the University of Grenoble Alpes, France providing the basic concept of the relation between Presentation and Research.
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.
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
Palestine last event orientationfvgnh .pptxRaedMohamed3
An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
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.
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.
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
2. Introduction
Before the twentieth century, medicines consisted mainly of
herbs and potions, and it was not until the mid-nineteenth
century that the first serious efforts were made to isolate and
purify the active principles of those remedies. Since then,
many naturally occurring drugs have been obtained and their
structures have determined.
These natural products sparked off a major synthetic effort
where chemists made literally thousands of analogues in an
attempt to improve on what nature had provided.
3. Introduction
An overall pattern for drug discovery and drug development
evolved, but there was still a high element of trial and error
involved in the process.
In recent years, rapid advances in the biological sciences have
resulted in a much better understanding of how the body
functions at the cellular and the molecular level.
As a result, most research projects in the pharmaceutical
industry or university sector now begin by identifying a
suitable target in the body and designing a drug to interact with
that target.
4. Generally, we can identify the following stages in drug discovery,
design, and development:
Drug discovery: Finding a lead
• Choose a disease
• Choose a drug target
• Identify a bioassay
• Find a ‘lead compound’
• Isolate and purify the lead compound if necessary
• Determine the structure of the lead compound if required
5. Drug design:
• Identify structure–activity relationships (SARs)
• Identify the pharmacophore
• Improve target interactions (pharmacodynamics)
• Improve pharmacokinetic properties
Drug development:
• Patent the drug
• Carry out preclinical trials (drug metabolism, toxicology,
formulation and stability tests, pharmacology studies, etc.)
• Design a manufacturing process
(chemical and process development)
• Carry out clinical trials
• Register and market
7. 1. Choosing a disease
The first step of drug discovery is of course choosing a disease.
Pharmaceutical companies have to consider economic factors, as
well as medical ones. A huge investment has to be made in the
research and development of a new drug. Therefore, companies
must ensure that they get a good financial return for their
investment.
2. Choosing a drug target
Once a therapeutic area has been identified, the next stage is to
identify a suitable drug target (e.g. receptor, enzyme, nucleic acid,
etc.).
Target specificity: Selectivity is important for drugs acting on
targets within the body. Enzyme inhibitors should only inhibit the
target enzyme and not some other enzyme.
8. 3. Identify Bioassay
Choosing the right bioassay or test system is crucial to the
success of a drug research program. The test should be simple,
quick, and relevant, as there are usually a large number of
compounds to be analyzed.
Human testing is not possible at such an early stage, so the test
has to be done in vitro (i.e. on isolated cells, tissues, enzymes,
or receptors) or in vivo (on animals).
Thus, in vitro tests are usually carried out first to determine
whether a drug interacts with its target, and in vivo tests are
then carried out to test pharmacokinetic properties.
9. Bioassay Techniques
High-throughput Screening (HTS):
Robotics and the miniaturization of in vitro tests on genetically modified cells has
led to a process called high-throughput screening (HTS), which is particularly
effective in identifying potential new lead compounds.
This involves the automated testing of large numbers of compounds versus a large
number of targets; typically, several thousand compounds can be tested at once in
30–50 biochemical tests.
10. Other techniques:
Screening by NMR
More recently, nuclear magnetic resonance (NMR)
spectroscopy has been used to detect whether a compound binds
to a protein target.
Affinity Screening
Surface Plasmon Resonance
Scintillation Proximity Assay
Isothermal Titration Calorimetry
Virtual Screening
11. 4. Finding a Lead Compound
Once a target and a testing system have been chosen, the next
stage is to find a lead compound—a compound which shows
the desired pharmacological activity.
The level of activity may not be very great and there may be
undesirable side effects, but the lead compound provides a start
for the drug design and development process.
12. There are various ways in which a lead compound might be discovered:
Screening of Natural Products
The Plant Kingdom
Microorganisms
Marine Sources
Animal Sources
Venoms and Toxins
Medical Folklore
Screening of Synthetic Compound “Libraries”
Existing Drugs
“Me Too” and “Me Better” Drugs
Enhancing a Side Effect
Starting from Natural Ligand or Modulator
Natural Ligands for Receptors
Natural Substrate for Enzymes
Enzyme Products as Lead Compounds
Natural Products as Lead Compounds
Combinatorial and Parallel Synthesis
Computer-aided Drug Design of Lead Compound
13. 5. Isolation and Purification
If the lead compound (or active principle ) is present in a
mixture of compounds from a natural source or a
combinatorial synthesis, it has to be isolated and purified.
The ease with which the active principle can be isolated and
purified depends very much on the structure, stability, and
quantity of the compound.
14. 6. Structure Determination
In the past, structures had to be degraded to simpler
compounds, which were further degraded to recognizable
fragments. From these scraps of evidence, a possible structure
was proposed, but the only sure way of proving the proposal
was to synthesize the structure and to compare.
Today, structure determination is a relatively straightforward
process. Methods used to determine structure includes X-ray
crystallography, NMR spectroscopy, mass spectroscopy, etc.
16. Drug Design - Introduction:
Once the lead compound has been discovered, it can be used
as the starting point for drug design.
There are various aims in drug design. The eventual drug
should have a good selectivity and level of activity for its
target, and have minimal side effects. It should be easily
synthesized and chemically stable. And finally, it should be
non-toxic and have acceptable pharmacokinetic properties.
17. Purpose of Drug Design
1.To improve the selectivity of the drug
The main purpose of the drug is to get the therapeutic effect
with lesser toxicity. In some cases, it has been observed that the
effective dose of the drug does not only show therapeutic
activity but also some toxicity. So sometimes it is important to
improve the selectivity of drug to reduce the toxicity or adverse
reaction.
For example, selective β1- blockers are safer for patients with
lung disease than nonselective β-blockers.
18. 2. To alter the ADME of the drug
Absorption:
Oral route of administration is always a convenient route.
But sometimes it is not possible for a drug to be given in
oral route because of poor absorption or lack of stability in
GIT.
19. Distribution:
Molecular modification can help to alter the distribution of the
drug.
For example, thiopental is developed from pentobarbital by
replacing one oxygen atom with sulfur.
Metabolism:
We can control the action of the drug by increasing or decreasing
the metabolism rate to shorten or prolong action of the drug
respectively.
For example, the development of procainamide from procaine.
Elimination:
Elimination can be a good factor to consider for molecular
modification. A drug should have an acceptable elimination rate.
If the drug is too polar, it is likely to be eliminated rapidly.
20. 3. To achieve more desired (drug-like) properties and less
toxicity
One of the main purposes of drug designing is to achieve more
desirable properties like potency, less toxicity, and specificity.
4. Modification to reduce cost
Modification of the lead compound is often done to make the
drug more affordable.
For example, the synthetic diethylstilbestrol offers more
affordability compared to the natural estrogenic hormones.
21. Identify structure–activity relationships (SARs):
Once the structure of a lead compound is known, the medicinal
chemist moves on to study its structure–activity relationships
(SAR). The aim is to identify those parts of the molecule that
are important to biological activity and those that are not.
In order to study the structure activity relationship of a lead
compound, we first have to identify which functional groups of
the lead that takes part in the binding interactions with the
target. In traditional approach, we develop analogs of the lead
compound by changing/modifying different functional groups
of the drug and test the activity of each of these analogs.
22. Identification of Pharmacophore:
Once it is established which groups are important for a
drug’s activity, it is possible to move on to the next stage—
the identification of the pharmacophore.
The pharmacophore summarizes the important binding
groups that are required for activity, and their relative
positions in space with respect to each other.
23. Drug optimization: Strategies in drug design
Once the important binding groups and pharmacophore of
the lead compound have been identified, it is possible to
synthesize analogues that contain the same
pharmacophore.
But why is this necessary? If the lead compound has useful
biological activity, why bother making analogues?
The answer is that very few lead compounds are ideal.
Most are likely to have low activity, poor selectivity, and
significant side effects.
They may also be difficult to synthesize, so there is an
advantage in finding analogues with improved properties.
24. This can be done by:
1. Variation of substituents ( alkyl, aromatic)
2. Extension of the structure
3. Chain extension/contraction
4. Ring expansion/contraction
5. Ring variation
6. Ring fusions
7. Isosteres and bioisosteres
8. Simplification of the structure
9. Rigidification of the structure
10. Conformation Blockers
11. Structure based drug design (Computer based drug design)
12. Drug design by NMR spectroscopy
13. Designing drugs to interact with more than one target
25. Optimizing hydrophilic/hydrophobic properties
The relative hydrophilic/hydrophobic properties of a drug are
crucial in influencing its solubility, absorption, distribution,
metabolism, and excretion (ADME).
Drugs which are too polar or too hydrophilic do not cross the
cell membranes of the gut wall easily. One way round this is to
inject them, but they cannot be used against intracellular targets
as they will not cross cell membranes. They are also likely to
have polar functional groups which will make them prone to
plasma protein binding, metabolic phase II conjugation
reactions, and rapid excretion.
26. Very hydrophobic drugs fare no better. If they are administered
orally, they are
likely to be dissolved in fat globules in the gut and will be poorly
absorbed. If they are injected, they are poorly soluble in blood and
are likely to be taken up by fat tissue, resulting in low circulating
levels.
It has also been observed that toxic metabolites are more likely to
be formed from hydrophobic drugs.
27. Strategies to optimize hydrophilic/hydrophobic properties
of the drug
1. Masking polar functional groups to decrease polarity
2. Adding or removing polar functional groups to vary polarity
3. Varying hydrophobic substituents to vary polarity
4. Variation of N-alkyl substituents to vary pKa
5. Variation of aromatic substituents to vary pKa
6. Bioisosteres for polar groups
28. Drug development:
• Patent the drug
• Carry out preclinical trials (drug metabolism, toxicology,
formulation and stability tests, pharmacology studies, etc.)
• Design a manufacturing process
(chemical and process development)
• Carry out clinical trials
• Register and market
29. Formulation Studies:
Involve developing a preparation of the drug which is both
stable and acceptable to the patient. ( Tablet, capsule, IV)
Pre-formulation involves characterization of a drugs physical,
chemical & mechanical properties in order to choose what
other ingredients should be used in the preparation.
Formulation studies then must consider such factors like
particle size, salt form, crystal polymorphism, pH and
solubility, as all of these can influence bioavailability.
Pharmacology Studies:
- Drugs mechanism of action
- Dose response relationship & drugs duration of action.
30. Clinical Trials:
Phase 1: Takes about a year, involves 200-300 healthy
volunteer. Drugs safety, pharmacokinetics and dose levels.
Phase 2: Last 2 years. Carried on patients to establish weather
the drug has the therapeutic property claimed and to study
pharmacokinetic property and short term safety and to define
best doses regimen.
Phase 3: Take about three years. Carried out same as phase 2
and different parts of the world with double blind process. (
comparing the activity of drug with placebo)
Phase4: The drug is marketed and prescribed, and still
monitored for any rare and unexpected side effects.
33. Prepared By: Team Discipulus Magister
A Team Of Researchsio
Masruk Alam
Southeast University,
Pharmacy Dept.
Member,
Researchsio
Riaz Mahmood
Southeast University,
Pharmacy Dept.
Member & Ambasaador
Researchsio
Editor's Notes
In choosing a disease, researchers has to focus on diseases that are important in the developed world because this is the market best able to afford new drugs.
SARS-CoV-2, virus has an envelope around it which consists of a lipid bilayer - membrane, envelope, and spike structural proteins are anchored in it. The viral spike protein first binds with the ACE2 receptor of the host cell, and the virus can then enter the cell. A host cell’s protease TMPRSS2 is essential for entry of SARS-CoV-2 into the host cell. Inside host cell, the RNA-dependent-RNA-polymerase which makes copies of the viral RNA.
Serendipity and the Prepared Mind . Computerized Searching of Structural Database. Fragment-based Lead Discovery
For example, protein or polypeptide drugs break down in GIT, and therefore are not orally active. Modification of the drug molecule is sometimes required to improve the absorption from GIT.
procaine was known to have useful anti-arrhythmic properties, but it is an ester which can be easily hydrolyzed in plasma or liver. By simply substituting the ester structure with the amide structure, we can get the procainamide which exhibits prolonged action in body.