1) Combinatorial chemistry allows for the simultaneous synthesis of multiple compounds using a set of building blocks. This approach can generate thousands of compounds quickly and efficiently.
2) Traditional synthesis is slow, producing one compound at a time. Combinatorial chemistry addresses this through parallel and split-and-mix techniques, generating library of compounds on solid resin beads or in solution.
3) The library is then screened to identify compounds with desired biological activity, accelerating drug discovery. Encoding methods like positional or chemical tagging are used to identify the active compounds within complex mixtures.
ENZYME INHIBITION THE MOST IMPORTANT TOPIC FOR BIOLOGY AS WELL AS CHEMISTRY PEOPLES. WE HAVE HERE COVERED FOR THE PHARMA STUDENTS THIS WILL MAKE THEM EASY AS WE ARE COLLECTED ALL THE DATA A SINGLE PLACE WICH COVERS ALL THE COTENTS.
stereochemistry and drug action ; basic introduction about stereochemistry and stereoisomers ; pharmacokinetic and pharmacodynamics concept of stereochemistry ; easson Stedman hypothesis ; stereo selectivity criteria .
ENZYME INHIBITION THE MOST IMPORTANT TOPIC FOR BIOLOGY AS WELL AS CHEMISTRY PEOPLES. WE HAVE HERE COVERED FOR THE PHARMA STUDENTS THIS WILL MAKE THEM EASY AS WE ARE COLLECTED ALL THE DATA A SINGLE PLACE WICH COVERS ALL THE COTENTS.
stereochemistry and drug action ; basic introduction about stereochemistry and stereoisomers ; pharmacokinetic and pharmacodynamics concept of stereochemistry ; easson Stedman hypothesis ; stereo selectivity criteria .
Combinatorial chemistry by Sunil Yadav SD Bihani College sri gangangar sunilkamal1045
The Combinatorial Chemistry is a scientific method in which a very large number of chemical entities are synthesized by condensing a small number of chemical compounds together in all combinations defined by a small set of chemical reactions.
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.
Chronopharmacology is the branch of science which deals with the pharmacological action of a drug in relation to biological rhythm.
(Chronos: time; Pharmacon: drug; Logos: study)
It is concerned with the effects of drugs upon the timing of biological events and rhythms.
It is important to enhance the therapeutic efficacy, optimization of drug effects, minimization of adverse effects by using timing medications in relation to biological rhythm.
History:
Jean-Jaques d’Ortous de Mairan: Described circardian rhythm in plants in the 18th century.
Franz Halberg : coined the term ‘Circardian’ in 20th century (about 24 hr or about a day)
Franz Halberg : Founder of Chronobiology.
Biological Rhythm:
Biological rhythm: It is the determined rhythmic biological process or function within a defined time period.
TYPES OF RHYTHM
Circadian (last for 24 hr) – Sleep wake cycle
Infradian (> 24 hr) – Menstrual cycle
Ultradian (< 24 hr) – Neuronal firing time
Biological Clock:
An internal biological clock located in mammals, in the suprachiasmatic nucleus of the hypothalamus (SCN), delivering its message of time throughout the body.
It is responsible for circadian rhythms and annual/seasonal rhythm.
The SCN uses its connections with the autonomic nervous system for spreading its time-of-day message, either by setting the sensitivity of endocrine glands (thyroid, adrenal, ovary) or by directly controlling an endocrine output of pineal gland (i.e. melatonin synthesis)
Application:
Chronotherapy found useful in
Asthma therapy, Strokes, Sleep disorders, GI tract disorders, Allergies, Oncology etc
Recent Advances:
Casein Kinase 1 (CK-1) inhibitor: Potential new drug
Reset the circadian clock enzymes.
Uses: Jet lag, sleep disorder, bipolar disorder
Animal trials completed.
Clinical trials are awaited.
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
It is the presentation for Combinatorial Chemistry. this presentation should be helpful for B. Pharm students. It includes introduction, types, applications, advantages and disadvantages.
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.
Combinatorial chemistry and high throughputscreeningSaikiranKulkarni
Combinatorial chemistry is a collection of techniques which allow for the synthesis of multiple compounds at the same time.
Combinatorial chemistry is one of the important new methodologies developed by researchers in the pharmaceutical industry to reduce the time and costs associated with producing effective and competitive new drugs, By accelerating the process of chemical synthesis, this method is having a profound effect on all branches of chemistry, but especially on drug discovery.
Combinatorial chemistry by Sunil Yadav SD Bihani College sri gangangar sunilkamal1045
The Combinatorial Chemistry is a scientific method in which a very large number of chemical entities are synthesized by condensing a small number of chemical compounds together in all combinations defined by a small set of chemical reactions.
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.
Chronopharmacology is the branch of science which deals with the pharmacological action of a drug in relation to biological rhythm.
(Chronos: time; Pharmacon: drug; Logos: study)
It is concerned with the effects of drugs upon the timing of biological events and rhythms.
It is important to enhance the therapeutic efficacy, optimization of drug effects, minimization of adverse effects by using timing medications in relation to biological rhythm.
History:
Jean-Jaques d’Ortous de Mairan: Described circardian rhythm in plants in the 18th century.
Franz Halberg : coined the term ‘Circardian’ in 20th century (about 24 hr or about a day)
Franz Halberg : Founder of Chronobiology.
Biological Rhythm:
Biological rhythm: It is the determined rhythmic biological process or function within a defined time period.
TYPES OF RHYTHM
Circadian (last for 24 hr) – Sleep wake cycle
Infradian (> 24 hr) – Menstrual cycle
Ultradian (< 24 hr) – Neuronal firing time
Biological Clock:
An internal biological clock located in mammals, in the suprachiasmatic nucleus of the hypothalamus (SCN), delivering its message of time throughout the body.
It is responsible for circadian rhythms and annual/seasonal rhythm.
The SCN uses its connections with the autonomic nervous system for spreading its time-of-day message, either by setting the sensitivity of endocrine glands (thyroid, adrenal, ovary) or by directly controlling an endocrine output of pineal gland (i.e. melatonin synthesis)
Application:
Chronotherapy found useful in
Asthma therapy, Strokes, Sleep disorders, GI tract disorders, Allergies, Oncology etc
Recent Advances:
Casein Kinase 1 (CK-1) inhibitor: Potential new drug
Reset the circadian clock enzymes.
Uses: Jet lag, sleep disorder, bipolar disorder
Animal trials completed.
Clinical trials are awaited.
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
It is the presentation for Combinatorial Chemistry. this presentation should be helpful for B. Pharm students. It includes introduction, types, applications, advantages and disadvantages.
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.
Combinatorial chemistry and high throughputscreeningSaikiranKulkarni
Combinatorial chemistry is a collection of techniques which allow for the synthesis of multiple compounds at the same time.
Combinatorial chemistry is one of the important new methodologies developed by researchers in the pharmaceutical industry to reduce the time and costs associated with producing effective and competitive new drugs, By accelerating the process of chemical synthesis, this method is having a profound effect on all branches of chemistry, but especially on drug discovery.
Important for D. Pharmacy, B. Pharmacy and M. Pharmacy.
A brief introduction to the basic of pilot plant scale up and its objectives, significance, applications and importance
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.
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.
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.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
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.
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.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
Francesca Gottschalk - How can education support child empowerment.pptx
Combinatorial Chemistry Sunil Yadav
1. PREPARED BY: GUIDED BY:
SUNIL YADAV Prof. Mahesh Kumar Kataria
M.Pharm HOD Department of Pharmaceutics.
Seth G. L. Bihani S. D. College of Technical Education
Institute of Pharmaceutical Sciences & Drug Research, Sri Ganganagar, Rajasthan 1
2. Combinatorial chemistry
Combinatorial chemistry (Combichem) is a collection of techniques which
allow for the synthesis of multiple compounds at the same time.
Conventional Reaction: A + B AB
Combinatorial Chemistry: A1- n + B1- n A1- n B1- n
This powerful new technology has begun to help pharmaceutical
companies to find new drug candidates quickly, save significant money in
preclinical development costs and ultimately change their fundamental
approach to drug discovery.
2
3. Need for Combichem
Problems with Traditional/Conventional Synthesis:
1 chemist 1 molecule
Can only make one molecule at a time.
Each synthesis very time consuming.
Multistep synthesis have loss at each step.
Purification of products very time-consuming between steps.
Yields can be low and produces very few molecules at a time for testing.
Slower lead generation.
Hundreds of molecules in a month are generated.
High risk of failure.
3
4. Need for Combichem
Benefits with Combinatorial Synthesis:
1 chemist multiple molecules
Can make multiple molecules at a time.
The time & cost associated with the generation & analysis of each
individual molecule is significantly less when compared to the time & cost
of an individual synthesis.
Yields can be high and produces many molecules at a time for testing.
Faster lead generation.
Thousands of molecules in a month are generated.
Low risk of failure.
Multiple molecules synthesized at a time.
4
5. Definition of Combichem
Combinatorial chemistry may be defined as the systematic and repetitive,
covalent connection of a set of different “building blocks” of varying
structures to each other to yield a large array of diverse molecular entities.
Combinatorial chemistry encompasses many strategies and processes for
the rapid synthesis of large, organized collections of compounds called
libraries. The collection is then tested for the biological activity. Finally the
active compound is identified and made in quantity as a single compound.
Thus the combinatorial chemistry approach has two phases:
1. Making a library.
2. Finding the active compound
5
6. History of Combichem
Although combinatorial chemistry has only really been taken up by the
industries since the 1990s, its roots can be seen as far back as the 1960s
when a researcher at Rockefeller University, Bruce Merrifield, developed a
way to make peptides by solid-phase synthesis.
Bruce Merrifield won the Nobel prize in chemistry in 1984 for his work on
solid-phase synthesis. During this time, automated peptide synthesizer
technology was in its infancy, and the preparation of individual peptides
was a challenge.
6
7. History of Combichem
The field in its modern dimensions only began to take shape in the 1980s,
when in 1984, research scientist H. Mario Geysen his coworker developed
a technique for synthesizing peptides on pin-shaped solid supports and in
1985, Richard Houghten developed a technique for creating peptide
libraries in tiny mesh "tea bags" by solid-phase parallel synthesis.
Another early pioneer was Dr. Árpád Furka (considered to be one of the
fathers of combinatorial synthesis) who introduced the commonly used
split-and-pool method in 1988, which is used to prepare millions of new
peptides in only a couple of days and also for synthesizing organic
libraries.
7
8. Principle of Combichem
To prepare a large number of different compounds at the same time Instead
of synthesizing compounds in a conventional one at a time manner and
then to identify the most promising compound for further development by
high throughput screening (HTS).
In combinatorial synthesis different compounds are generated
simultaneously under identical reaction conditions in a systematic manner,
so that ideally the products of all possible combinations of a given set of
starting materials (termed building blocks) will be obtained at once. The
collection of these finally synthesized compounds is referred to as a
combinatorial library. The library is then screened for useful properties and
the active compounds are identified.
8
9. Principle of Combichem
Example:
A + B AB (A) Conventional approach
A1 - n + B1 - n A1 – n B1 – n or (B) Combinatorial approach
A1 B1 A1B1 A1B2 A1Bn
A2 B2 A2B1 A2B2 A2Bn
An Bn AnB1 AnB2 AnBn
(A) In a conventional synthesis one starting material A reacts with one reagent
B resulting in one product AB.
(B) In a combinatorial synthesis different building blocks of type A (A1-An)
are treated simultaneously with different building blocks of type B (B1-Bn)
according to combinatorial principles, each starting material A reacts
separately with all reagents B resulting in a combinatorial library A1-nB1-n.
9
10. Types of Combichem
Combinatorial chemistry is of two types:
SOLID PHASE COMBINATORIAL CHEMISTRY
(Compound library synthesized on solid phase such as resin bead)
SOLUTION PHASE COMBINATORIAL CHEMISTRY
(Compound library synthesized in solvent in the reaction flask)
10
11. Solid phase Combichem
STEPS:
Attach the starting molecule to an inert solid/resin bead.
Addition of excess of reagents to the solution.
Separation of products (attached to resin beads) by simple filteration.
Cleavage & isolation of products from the beads.
REQUIREMENTS:
Solid support (Resin beads)
An anchor or linker.
A bond linking the substrate to the linker.
A means of cleaving the product from the linker at the end.
Protecting groups
11
12. Solid phase Combichem
EXAMPLES OF SOLID SUPPORTS:
Partially cross-linked polystyrene beads: Polystyrene is cross linked
with divinyl benzene, hydrophobic in nature, causes problems in peptide
synthesis due to peptide folding.
Sheppard’s polyamide resin - more polar.
Tentagel resin - similar environment to ether
Beads, pins and functionalised glass surfaces
CHARACTERISTICS OF SOLID SUPPORT:
Beads must be able to swell in the solvent used, and remain stable.
Most reactions occur in the bead interior.
12
Resin bead Swelling
Linkers
Starting material,
reagents and solvent
13. Solid phase Combichem
ANCHOR OR LINKER:
A molecular moiety which is covalently attached to the solid support,
and which contains a reactive functional group.
Allows attachment of the first reactant.
The link must be stable to the reaction conditions in the synthesis but
easily cleaved to release the final compound.
Different linkers are available depending on the functional group to be
attached and the desired functional group on the product.
Resins are named to define the linker e.g.
Merrifield resin
Wang resin
Rink amide resin
Photolabile anchors
Traceless anchors
13
14. Solid phase Combichem
PROTECTING GROUPS:
A protecting group is reversibly attached to the functional group to
convert it to a less reactive form.
When the protection is no longer needed, the protecting group is cleaved
and the original functionality is restored.
protecting group to be stable under the expected reaction conditions and
to be cleavable - if possible-at mild reaction conditions.
Some of the protecting groups most widely used in peptide synthesis
are:
Benzyl carbonyl (Z) group
t-butoxy carbonyl (Boc) group
9-fluorenyl methoxy carbonyl (Fmoc) group
14
15. Solid phase Combichem
ADVANTAGES OF SOLID PHASE SYNTHESIS:
Specific reactants can be bound to specific beads.
Beads can be mixed and reacted in the same reaction vessel.
Products formed are distinctive for each bead and physically
distinct.
Excess reagents can be used to drive reactions to completion.
Excess reagents and by products are easily removed.
Reaction intermediates are attached to bead and do not need to be
isolated and purified.
Individual beads can be separated to isolate individual products.
Polymeric support can be regenerated and reused after cleaving
the product.
Automation is possible
15
16. Solid phase Combichem
DISADVANTAGES OF SOLID PHASE SYNTHESIS:
Not all syntheses can be done solid phase.
Some molecules don’t attach well to beads
Some chemistry just doesn’t work in this fashion
Removal of product from bead, can be damaging to product if not
careful
Typically, kinetics not the same.
Reaction rates can be slower
Difficult to monitor the progress of reaction when the substrate and
product are attached to the solid phase.
Assessment of the purity of the resin attached intermediates is also
difficult.
Purifying the final product after cleavage from the resin also proves to
be a challenge.
16
17. Solution phase Combichem
All chemical reactions are conducted simultaneously, preferably in well-
ordered sets (arrays) of reaction vessels in solution.
Soluble polymer are used as support for the product.
Limitation
when numbers of reagents are taken together in a solution
it can result in several side reactions and
Lead to polymerization giving a tarry mass.
Rectification
A new approach is developed in which all chemical structure
combinations are prepared separately, in parallel on a giving building
block using an automated robotic apparatus.
17
18. Combinatorial techniques
There are mainly two combinatorial techniques:
SPLIT & MIX SYNTHESIS/PORTIONING-MIXING SYNTHESIS
(One bead-one compound library)
PARALLEL SYNTHESIS
(One vessel-one Compound library)
18
19. Split and mix synthesis
Good to generate large libraries.
Resin beads are split into
different vessels.
Then reacted, shuffled, and
split again.
1000 compund library prepared
from 10 building blocks in each
step 30 reaction steps.
19
20. Split and mix synthesis
ADVANTAGES OF SPLIT & MIX SYNTHESIS:
Only few reaction vessels are required.
Large libraries (up to 105 compounds) can be quickly generated.
DISADVANTAGES OF SPLIT & MIX SYNTHESIS:
Large amount of resin beads are required.
The amount of synthesized product is small.
Complex mixtures are formed.
Deconvolution or tagging required.
20
21. Parallel synthesis
Each compound is synthesized
in specific reaction vessel.
Each starting material is
reacted with each building
block separately.
Then product is split into
portions, reacted with different
buildind block separately again.
21
22. Parallel synthesis
ADVANTAGES OF PARALLEL SYNTHESIS:
It creates compounds individually & in its own vessels.
Identity of products are already known.
Each compound is substantially pure in its location.
DISADVANTAGES OF PARALLEL SYNTHESIS:
Applicable only for medium libraries.
Large amount of vessels required.
Large number of reactions to be performed.
22
23. Screening methods
Screening is the process of determining whether compounds in a
chemical library have a desired chemical or biological activity, without
necessarily identifying the precise chemical nature of the compound(s)
being screened.
METHODS OF SCREENING OF COMBICHEM LIBRARIES:
Test mixture in solution
Test individual compounds in solution
Test compounds on the bead
23
24. Encoding methods
The process of identification of active compound in a mixture of
compounds is known as Encoding.
METHODS OF ENCODING OF COMBICHEM LIBRARIES:
Positional encoding (iterative resynthesis and rescreening)
Chemical encoding (Tagging)
Electronic encoding
24