semester-wise structure for the m.pharm. in …. pharm.pdf · m.pharm. in pharmaceutical &...

Semester-wise structure for the

M.Pharm. in Pharmaceutical & Medicinal Chemistry (MPMC) programme

Semester I

No. Sub.

Code

Title of the

Course

Type of

Course

Credit

s

Contact

hours/week

ESE

(hour)

Weightage

(%)

CIE ESE

C/E/S L I.L P T P ST IA

1 MPMC

100

Communicati

on Skills

C 2 2 - - 2 - 30 20 50

2 MPMC

101

Biostatistics

and IPR

C 3 2 1 - 2 - 30 20 50

3 MPMC

102

Physical

Methods of

Analysis

C 3 2 1 - 2 - 30 20 50

4 MPMC

103 &

103P

Advanced

Organic

Chemistry I

C 3 + 3 2 1 4 2 4 30 20 50

5 MPMC

104 &

104P

Medicinal

Chemistry I

C 3 + 3 2 1 4 2 4 30 20 50

6 MPMC

151

Seminar 1 C 2 - 2 - 0.5 - - 20 80

7 MPMC

152

Lab Rotations S 2 2 - - - - - - -

Total Credits: Semester I 24 Credits

CIE Continuous Internal Evaluation; ESE End Semester Examination; ST Sessional Tests; IA

Internal Assessment, L Lectures, I.L. Integrated Learning involving Tutorials, Group

Discussions, Assignments, Field Work; P Practicals, Lab. work, Project, C Core, E Elective, S

Supportive.

In MPMC 152 Lab. Rotations, the student will rotate between different research laboratories

in his/her department and interact with the professor and the research students for a

period of total 30 hrs. At the end of the month the guide will be chosen based on mutual

consent of the student and professor. After selection of the research guide the student will

formulate his/her Seminar topic (MPMC 151).

Semester II

No. Sub.

Code

Title of the

Course

Type of

Course

Credit

s

Contact

hours/wee

k

ESE

(hour)

Weightage (%)

CIE ESE


1 MPMC

201

Advanced

Organic

Chemistry II

C 3 2 1 - 2 - 30 20 50

2 MPMC

202

Medicinal

Chemistry II

C 3 2 1 3 2 - 30 20 50

3 MPMC

210 &

210P

Basic

Molecular

Biology

C 3 + 3 2 1 4 2 4 30 20 50

4 MPMC

221 or

222 or

223 or

224

Elective-I E 3 2 1 - 2 - 30 20 50

5 MPMC

221 or

222 or

223 or

224

Elective-II E 3 2 1 - 2 - 30 20 50

6 MPMC

251

Research

Seminar 2 -

Literature

Review and

proposed

research plan

S 3 - 3 - 0.5 - - 20 80

7 MPMC

252

Minor

Research

Project

S 3 - 3 - - - - - -

Total Credits: Semester II –24

Semester III

No. Sub.

Code

Title of the

Course

Type of

Course

Credit

s

Contact

hours/wee

k

ESE

(hour)

Weightage (%)

CIE ESE


1 MPMC

300

Research

Methodology

C 3 2 1 - 2 - 30 20 50

The full time research work will commence from this Semester.

Total Credits: Semester III = 3 + 21 Research Credits = 24 Credits

Semester IV

This Semester is devoted totally to research which will culminate in the submission of a

thesis.

Total Credits: Semester IV = 24 Research Credits

Strong emphasis should be placed on the IPR value of the research work, beside

publications in peer reviewed journals of good impact factors. Students should be

encouraged to attend conferences, seminars where they will present their research work.

Detailed Syllabus

Theory Courses

Course No. MPMC 100 Title of the Course: Communication Skills Credits 2

Unit Course Content (Topics) Contact

Hours

Communication Skills

1.0 Grammar 6

1.1 Conditionals/Tenses, relative clauses, subject–verb agreement, passive voice

2.0 Written Communication 6

2.1 Discuss a topic of general interest, but related to science in about 300 words.

(Analyze, comment, argue, reflect, persuade, etc.) (can also be used for oral

presentations by the students, followed by discussion).

3.0 Oral Communication 3

3.1 Consulting a dictionary for correct pronunciation (familiarity with phonetics

symbols and stress-marks only)

3.2 (ii) Dialogue

4.0 Scientific Writing 6

4.1 Writing a Scientific Report on a project undertaken or an experiment

conducted (theory + practice)

5.0 Soft Skills

5.1 Gestures/ postures – Body language, gesture, posture. 2

5.2 Group discussion – Giving up of PREP, REP Technique, how body language

during group discussion.

2

5.3 Presentation skills: (i) How to make a Power Point presentation (ii) Body

language during presentation; Resume writing: Cover letter, Career

objectives, Resume writing (tailor made)

3

5.4 Mock Interview: Each student to face an interview and to demonstrate the

above taught skills.

2

Total 30

Course No MPMC 101. Title of the Course: Biostatistics and IPR Credits 3


Hours

Biostatistics

1.0 Collection and Organization of data 3

1.1 Graphical and pictorial presentation of data

1.2 Measures of central tendency and dispersion

1.3 Variance and standard deviation, relative error, coefficient of variation,

precision and accuracy

1.4 Sampling techniques: simple random sampling; stratification; estimation of

the mean and proportion.

2

2.0 Probability 6

2.1 Definition. Conditional probability and Bayes’ theorem. Probability

distributions: binomial, multinomial and Poisson distributions. Normal and

lognormal distributions. Use of normal distribution tables.

3.0 Regression 6

3.1 Linear regression and correlation, curvilinear regression, method of least

squares, curve fitting, Fiducial limits, probit and logit analysis

4.0 Parametric tests 6

4.1 Testing hypothesis, Types of error. Level of significance. Significance tests and

p-value

4.2 Tests of significance based on normal distribution, test of significance for

correlation coefficients, confidence interval for mean and regression

proportion.

5.0 Nonparametric tests 3

5.1 Nonparametric procedures: Chi square goodness of fit test, sign test, Mann-

Whitney test; Wilcoxon signed rank test.

6.0 Experimental designs 6

6.1 Randomization, completely randomized, randomized block and Latin square

designs, factorial design, cross over and parallel designs

6.2 Students should learn use of Minitab / R Software for data summary,

correlation, regression analysis, test of hypothesis and experimental design

Total of Biostatistics 32

IPR and Patents

7.0 Introduction to intellectual property rights: types of IP, patents, trademarks,

copyright and related rights, industrial design, traditional knowledge,

geographical indications, protection of new GMOs. International framework

for the protection of IP. IP as a factor in industry, relevance of IP to

biotechnology, and few case studies. Introduction to the history of GATT,

WTO, WIPO, and TRIPS.

7.1 Concept of prior art: invention in context of prior art, patent databases,

searching international databases, country wise patent searches (USPTO, EPO,

India etc.). Analysis and report formation.

7.2 Basics of Patents: types of patents, Indian Patent Act 1970, recent

amendments, filing of a patent application, precautions before patenting,

disclosure/non-disclosure. WIPO treaties, Budapest treaty, PCT and

implications, procedure for filing a PCT application

7.3 Patent filing and infringement: types of patent applications, provisional and

complete specifications, PCT and conventional patent applications,

international patenting requirements, procedure and costs, financial

assistance for patenting – introduction to existing schemes, publication of

patents – gazette of India, status in Europe and USA. Patenting by research

students, lecturers and scientists – university/organisation, rules in India and

abroad, credit sharing by workers, financial incentives.

Patent infringement – meaning, scope, litigation, case studies and examples.

Total of IPR and Patents 13

Total 45

Books

1. Pharmaceutical Statistics – Practical and Clinical Applications, Bolton S., Marcel Dekker,

Inc. N. Y. USA

2. Biostatistics: A Foundation for Analysis in Health Sciences, Wayne W Daniel, John Wiley &

Sons, Inc.

3. Introduction to Statistical Analysis, Dixon W. J. and Massey F. J., McGraw Hill, N.Y., USA.

4. Statistical Methods, Snedecor G. W. and Cochran W. G., Iowa State University Press,

Ames, Iowa.

Course No MPMC 102. Title of the Course: Physical Method of Analysis Credits 3


Hours

1.0 UV 4

1.1 Woodward-Fieser rules, UV spectra of aromatic and heterocyclic compounds,

optical rotatory dispersion and circular dichroism

2.0 IR and Raman Spectroscopy 6

2.1 FT technique, group frequencies, vibrational coupling, NIR spectroscopy,

scattering phenomena, Raman Spectroscopy, a brief of factors affecting

absorption frequencies

3.0 NMR and ESR 11

3.1 CW vs Pulse Experiments

3.2 Factors influencing chemical shift, coupling constant, types of couplings,

decoupling studies, shift reagents, spin-lattice and spin-spin relaxation,

nuclear Overhauser effect, spectral editing. Interpretation of NMR spectras.

CMR and factors affecting CMR shifts

3.2 Two-dimensional NMR

3.2 Proton-proton correlation through coupling, proton-heteronuclear

correlation, proton-proton correlation through space and chemical exchange,

carbon-carbon correlation

3.3 Theory and experimental techniques of ESR, hyperfine splitting, ESR

parameters

2

4.0 Mass Spectrometry 8

4.1 EI, CI, DI, MALDI, SELDI, SI and ESI

4.2 Mass analysis – TOF analysers, quadrupole mass filters, ion cyclotron

resonance, tandem mass spectrometers, HRMS

4.3 General Principles of fragmentation, energetic of dissociation, odd- and even-

electron ions, Stevenson’s rules, rearrangement vs simple cleavage, proximate

vs remote fragmentation, distonic ions, charge localization, characteristic

fragment ions and neutral fragments

4.4 Chemical analysis, molecular weight determination, molecular structure

determination, molecular formula determination

4.5 Isotopic analysis, quantitative analysis, mixture analysis

4.6 Chromatography-mass spectrometry, tandem mass spectrometry (MS-MS),

thermochemical determinations

5.0 X-Ray Diffraction 4

5.1 Introduction

5.2 Crystal Planes and miller indices

5.3 Bragg’s law of diffraction

5.4 Reciprocal Lattices

5.5 Powder method: Debye-Scherrer method, The powder diffractometer,

Indexing the powder patterns, use of X-ray powder patterns

5.0 Problems involving structure determination based on UV, IR, NMR and MS 10

Total 45

Books

1. Spectroscopy, Pavia D. L., Lapman G. M., Kritz G. S., Vyvyan J. R., Brooks/Cole Indian

Reprint.

2. Modern NMR Techniques for Chemistry Research, Derome A. E., Pergamon Press.

3. Spectroscopic Methods in Organic Chemistry, Williams D. H., Fleming I., Tata McGraw Hill.

4. Spectrometric Identification of Organic Compounds, Silverstein R. M., Bassler G. C.,

Morrill T. C., John Wiley.

Course No MPMC 103. Title of the Course: Advanced Organic Chemistry I Credits 3


Hours

1.0 Advanced Stereochemistry 24

1.1 Coverage of the basic concepts in stereochemistry – optical activity,

specific rotation, racemates and resolution of racemates, the Cahn-

Ingold-Prelog sequence rule, meso compounds, pseudo asymmetric

centres, pro-R, pro-S, axes of symmetry, Fischers D and L notation, cis-

trans isomerism, exo-endo, syn-anti nomenclature. Stereoselective and

stereospecific reactions. Conformational isomerism in acyclic systems.

Shape of six membered rings and effect of substituents and reactivity.

1.2 Chirality in systems lacking a stereogenic carbon atom

1.2.1 Point chirality – tertiary amines and phosphines

1.2.2 Axial chirality – allenes, biphenyls and binaphthyls

1.2.3 Helical structures – polynucleotides, polyamino acids, biaryls and

allenes

1.3 Methods for estimating ratios of stereoisomers in a mixture, separation

and identification of the individual components by NMR spectroscopy,

X-ray crystallography.

1.4 Nucleophilic attack on acyclic carbonyl compounds – Cram’s rule,

Felkin-Ahn rule. Locking effects in nucleophilic reactions at carbonyl

groups

1.5 Stereochemistry of important reactions leading to formation of alkenes

– Wittig and related reactions

1.6 Pericyclic Reactions: Electrocyclic, cylcoaddition, sigmatropic reactions.

Woodward Hoffmann rules, FMO approach, Hückels approach.

Stereochemical implications in pericyclic reactions.

2.0 Green Chemistry 5

2.1 History, need and the goals of green chemistry

2.2 Basic principles of green chemistry, illustrated with examples to discuss

issues of prevention of waste or minimize by-products, atom economy,

prevent and minimize formation of hazardous or toxic products, design

of safer chemical equivalents, selection of appropriate solvents, media,

separation agents, improve economy and efficiency of reactions by use

of microwaves, ultrasound etc., and use of renewable starting

materials.

3.0 Photochemistry 7

3.1 Interaction of radiation with matter, types of excitations, fate of excited

molecules, quantum yield, transfer of excitation energy

3.2 Determination of the rate constants of photochemical reactions, effect

of the intensity of light on the rate of photochemical reactions

3.3 Some photochemical reactions involving alkenes, carbonyl compounds

and aromatic compounds

4.0 Combinatorial Chemistry 9

4.1 Introduction, advantages and planning combinatorial synthesis

4.2 Solid phase and solution phase synthesis

4.3 Supports, linkers, and tags

4.4 Deconvolution and iteration

4.5 Parallel synthesis, multistep – convergent and sequential synthesis,

multicomponent reactions

Total 45

Books

1. Stereochemistry of carbon compounds, Eliel E, Wilen S H, Manden L N, Wiley.

2. Stereochemistry of Organic Compounds, Nasipuri D, Wiley Eastern.

3. Advanced Organic Chemistry, Carey FA and Sundberg RJ, Part A and B, Springer

4. Introduction to Green Chemistry, Ryan M. A., Tinnesand M., American Chemical Society

(Washington).

5. Combinatorial Chemistry; Synthesis and Application, Eds., Wilson S. R. Czarnik A. W.,

Wiley: New York.

6. Organic Chemistry, Clayden J, Greeves N, Warren S, Wothers P, Oxford University Press.

7. Stereoselective Synthesis, Atkinson R S, John Wiley & Sons.

8. Molecular Photochemistry, Turro N J, Publisher W A Benjamin.

9. Pericyclic Reactions, Mukherjee S M, McMillan Press.

Practical Courses

Course No MPMC 103P. Title of the Course: Advanced Organic Chemistry I Credits 3


Hours

1.1 Friedel crafts alkylation: t-butyl alcohol to t-butylchloride to t-butylbenzene

1.3 Friedel crafts acylation: phthalic anhydride to o-benzoylbenzoicacid to

anthraquinone

2.1 Wolff Kischner reduction: acetophenone to ethylbenzene

2.2 LAH reduction: cyclohexanone to cyclohexanol

2.3 Oxidation reduction: p-nitrotolune to p-nitrobenzoic acid to p-aminobenzoic acid

3.1 Hydroquinone to quinone to triacetoxybenzene

3.2 Hydroquinone to hydroquinone diacetate to 2,5-dihydroxyacetophenone

4.1 Napthalene to nitronapthalene to 4-nitronapthylamine

5.1 Mannich reaction of acetophenone

6.1 Anthranilic acid to o-chlorobenzoic acid to N-phenylanthranilic acid to acridone

7.0 Synthesis of heterocycles:

7.1 Aniline to quinoline

7.2 Urea to barbituric acid

7.3 Resorcinol to 7-hydroxy-4-methyl coumarin

7.4 Cyclohexanone to 1,2,3,4-tetrahydrocarbazole

7.5 o-phenylenediamine to benzimidazol

7.6 o-phenylenediamine to benzotriazole

7.7 Benzil to diphenylquinazoline

7.8 Acetylacetone to 3,5-dimethypyrazole

8.0 Grignard reaction, enamine synthesis and its acylation, NaBH4 reduction,

hydroboration oxidation, Green synthesis could also be easily incorporated in

the practical program

Total 60

Fifteen syntheses to be done during the Semester which will comprise 5 single stage

synthesis, 5 two stage synthesis and 5 hetereocycles.

Course No MPMC 104. Title of the Course: Medicinal Chemistry I

Credits 3


Hours

1.0 Drug Discovery 5

1.1 Historical perspective

1.2 Lead Discovery

1.3 Lead Modification – identification of the pharmacophore, functional

group modification, privileged structures and drug-like molecules,

modifications to increase potency and the therapeutic index,

modifications to increase oral bioavailability

2.0 Receptors 10

2.1 Basic ligand concepts – agonist, antagonist, partial agonist, inverse

agonist, efficiency and potency

2.2 Interactions (Forces) involved in drug-receptor complexes

2.3 Receptor theories – occupancy theory, rate theory and activation

theory

2.4 Receptor classification – the four superfamilies

2.5 Receptor binding assays- measurement of Kd, Bmax and IC50

2.6 Topographical and stereochemical considerations in drug –receptor

interactions

3.0 Prodrugs and Drug Delivery Systems 8

3.1 Enzyme activation of drugs, utility of prodrugs – aqueous solubility,

absorption and distribution, site specificity, instability, toxicity, poor

patient acceptability, formulation problems.

3.2 Carrier-linked prodrugs – carrier linkages for various functional groups,

carrier-linked bipartite prodrugs, macromolecular drug carrier systems,

tripartite prodrugs, mutualprodrugs, bioprecursor prodrugs (hydrolytic

activation, elimination activation, oxidative activation, reductive

activation, nucleotide activation, phosphorylation activation, sulfation

activation and decarboxylation activation).

4.0 Enzymes 8

4.1 Introduction to enzymes, binding site, specificity of enzyme catalyzed

reactions and rate acceleration, MichaelisMenten kinetics and methods

for plotting enzyme kinetic data

4.2 Mechanisms of enzyme catalysis – covalent catalysis, acid-base

catalysis, electrostatic catalysis, some examples of the mechanisms of

enzyme catalysis

4.3 Coenzyme catalysis – pyridoxal 5’-phosphate (racemases,

decarboxylases, aminotransferases), nictoinamide and flavin (two-

electron mechanism, carbanion followed by two one-electron transfers,

one-electron mechanism and hydride mechanism), folic acid and

thiamine (one carbon transfer reactions).

4.4 Enzyme therapy

5.0 Discovery, development and mechanistic aspects of selected classes

such as antibiotics, anticancer, antiviral, CVS, CNS, and GIT disorders

14

Total 45

Books

1. The Organic Chemistry of Drug Design and Drug Action, Silverman R. B., Academic Press.

2. Textbook of Drug Design and Discovery, Eds. Krogsgaard-Larsen P., Liljefors T., Madsen U.,

Taylor & Francis.

3. Drug Discovery – A History, Sneader W., Wiley.

4. Medicinal Chemistry: An Introduction, Thomas G, Wiley.

5. Drug Discovery – A History, Sneader W, John Wiley & Sons, Ltd.

Course No MPMC 104P. Title of the Course: Medicinal Chemistry I Credits 3


Hours

1.0 Measurement of logP of a poorly water soluble and a highly water soluble drug

2.0 Determination of the pKa of a drug (weak acid and weak base) by

potentiometric titration and by UV/visible spectroscopy

3.0 Determination of Km and Vmax for the esterase catalyzed hydrolysis of p-

nitrophenyl acetate by plasma esterases. Can also include inhibition of the

reaction by paraoxon and determination of IC50

4.0 Estimation of two drugs by simultaneous equation method and by absorbance

ratio method.

5.0 Synthesis of some drugs for e.g. thiazide and hydrothiazide derivatives

involving multistep reactions.(Students should learn to monitor the reaction by

TLC, separate the main product from impurities by column chromatography

and learn use of IR and 1H and

13C NMR to check the structures of the

intermediates and the final compounds). Comparison of microwave versus

conventional synthesis for two different reactions with respect to time

requirements and overall yield comparison

6.0 Resolution of racemic mixtures of acidic and basic compounds by formation of

diastereomers, e.g. RS-warfarin using (-) brucine

7.0 Synthesis of prodrugs of some common drugs and study of their decomposition

(kinetics) to the parent drug

8.0 Separation of drug and metabolites from plasma/urine. e.g. if volunteers are

given coumarin and 0-3 hrs urine is collected, it will have both coumarin and 7-

hydroxy coumarin (metabolite is present as glucuronide and has to be acid-

hydrolysed before HPLC injection)

9.0 Isolation of microsomes from liver tissue by calcium aggregation method.

Determination of protein content by Biuret method/Lowry method (BSA as

standard), determination of CYP content using CO binding by method of Omura

and Sato. Determination of catalytic competence using p-nitrophenol to p-

nitrocatechol reaction in presence of NADPH by RP-HPLC. Can also include

inhibition of the reaction by antipyrine or SKF-525 or chlorzoxazone.

10.0 Isolation of glutathione S-transferase fraction from liver tissue. Determination

of protein content (as above) and assay for 2,4-dichoronitrobenzene-

glutathione conjugate formation in the presence of reduced glutathione by

following change in absorbance with respect to time. Can also study inhibition

of reaction by ethacrynic acid or styrene oxide

11.0 Isolation of crude fraction of xanthine oxidase from rat liver. (involves heat

precipitation, solvent fractionation and ammonium sulfate precipitation) and

monitoring xanthine to uric acid formation by UV

Total 60

Any two from 9.0 to 11.0 to be conducted in a given Semester

Course No MPMC 151 Title of the Course: Seminar 1 Credits 2

The student in consultation with his/her research guide will choose a topic related to his/her

area of research and will deliver a Seminar at a date and time fixed by the department, that

should be attended by all students in the department, the research guide, the HOD and

other faculty of the Department. The Seminar will be of 25 minutes duration, followed by a

discussion. The student will be evaluated by all faculty members under the following

parameters: coverage of literature, presentation skills, defence and the seminar report (the

report should be handed in by the student the next day after the delivery of the seminar

and a copy of the seminar should be housed in the library). The final marks will be the

average of the marks given by the faculty.

In MPMC 152 Lab. Rotations, the student will rotate between different research

laboratories in his/her department and interact with the professor and the research

students for a period of total 30 hrs. At the end of the month the guide will be chosen

based on mutual consent of the student and professor. After selection of the research

guide the student will formulate his/her Seminar topic (MPMC 151).

Theory Courses for Semester II

Course No MPMC 201. Title of the Course:Advanced Organic Chemistry II Credits 3


Hours

1.0 Catalysis & Organometallics in Organic Synthesis 16

1.1 Types of catalysis, heterogeneous and homogenous catalysis,

advantages and disadvantages, catalytic cycles

1.2 Heterogeneous catalysis – preparation, characterization, kinetics,

supported catalysts, catalyst deactivation and regeneration, some

examples of heterogeneous catalysis used in synthesis of drugs.

1.3 Homogenous catalysis, hydrogenation, hydroformylation,

hydrocyanation, Wilkinson catalysts, chiral ligands and chiral induction,

Ziegler-Natta catalysts, some examples of homogenous catalysis used in

synthesis of drugs

1.4 Phase transfer catalysis - theory and applications

1.5 Introduction, Classification of organometallic compounds based on

hapticity and polarity of the M-C bond. Nomenclature and general

characters. Synthesis, stability and decomposition pathways.

1.6 Transition metal π-complexes with unsaturated organic molecules,

carbon monoxide, alkenes, alkynes, allyl, dienes, cyclopentadienyl,

arene complexes, preparation, properties, nature of bonding and

structural features, important reactions relating to nucleophilic attack

on ligands and to organic synthesis. Basic organometallic reactions

covering oxidative reactions, migratory reactions, insertions, extrusion,

additions, eliminations – their mechanisms and stereochemistry.

2.0 Synthon Approach and Applications 8

2.1 Retrosynthesis and its advantages, rules for dissection of molecules,

meaning of the term, disconnection, FGI, FGA and synthons, guidelines

for the order of events

2.2 C-X disconnections; C-C disconnections – alcohols and carbonyl

compounds; 1,2-, 1,3-, 1,4-, 1,5-, 1,6-difunctionalized compounds

2.3 Strategies for synthesis of three, four, five and six-membered rings

2.4 Strategies for synthesis of aromatic and saturated heterocycles

3.0 Protective Groups in Organic synthesis 4

3.1 Protective groups for hydroxyl, amino, carbonyl, carboxyl and thiol

functionalities

3.2 Synthetic equivalent groups

3.3 Protection and deprotection concepts

3.4 Selected applications

4.0 Asymmetric Synthesis 8

4.1 Introduction and need; chiral synthesis using chiral pool, chiral

auxiliaries, chiral catalysts

4.2 Enzymes, chiral solvents and whole organisms

4.3 Analytical methods of determining purity of stereoisomers

4.4 Applications in industry

5.0 Total synthesis of some drug molecules and natural products (like

reserpine, prostaglandins, taxol, estrone, epothiolone etc) as discussed

by Nicolaou and Sorensen in their books “Classics in Total Synthesis”.

9

Total 45

Books

1. The Organometallic Chemistry of the Transition Metals, Crabtree R. H., John Wiley

2. Transition Metals in Synthesis of Complex Organic Molecules, Hegedus L., University

Science Books.

3. Homogenous Transition Metal Catalysis, Masters C., Chapman & Hall.

4. Principles and Practice of Heterogenous Catalysis, Thomas J. M., Thomas M. J., John Wiley

5. Principles of Asymmetric Synthesis, Gawley R. E., Aubrey J, Elsevier.

10. Greene’s Protective Groups in Organic Synthesis, Wuts, P. G. M., Green T. W., Wiley

11. Organic Synthesis – The Disconnection Approach, Stuart, W., Wiley.

12. Classics in Total Synthesis, Nicolaou K C and Sorensen E J, Wiley-VCH.

13. The logic of chemical synthesis, Corey E J and Cheng X-M, John Wiley and Sons.

Course No: MPMC 202. Title of the Course : Medicinal Chemistry II Credits 3


Hours

1.0 Enzyme Inhibition 12

1.1 Coverage of basic aspects of enzyme kinetics, catalysis, transition-state

theory.

1.2 Drug Resistance through alterations of drug uptake, overproduction of

enzyme, alterations of the enzyme active site, overproduction of the

substrate or new pathways for formation of the product

1.3 Drug synergism, concepts and mechanisms.

1.4 Reversible enzyme inhibitors – competitive inhibition, non-competitive

inhibition, uncompetitive inhibition with suitable examples. Detection

of type of inhibition by suitable plotting methods. Concepts of IC50 and

Ki.

1.5 Slow-tight binding inhibitors, covalent enzyme inhibitors and

mechanism-based inhibitors with suitable examples. Concept of Kinact

and Ki for irreversible inhibitors

2.0 QSAR 14

2.1 Historical Aspects

2.2 Electronic Effects- the Hammett equation, lipophilic effects,

experimental measurement of lipophilicity, logP and logD, effect of

ionization on logP, calculation of logP and logD, Steric effects- the Taft

equation

2.3 Hansch Analysis, Free-Wilson method, Topliss operational scheme

2.4 Basics of regression analysis - linear and multilinear regression,

introduction to PCA, PCR, PLS, ANN and GFA. Correlation coefficients

(r2 and r

2pred), F-test, standard error, validation methods like cross-

validation by calculation of q2, boot-strap analysis and randomization.

Application domain for predictions using a QSAR model.

2.5 Design of training and test sets using factorial design

3.0 Peptides and Peptidomimetics 6

3.1 Coverage of peptide structure, biosynthesis of peptides and solid-

phase/solution synthesis of peptides.

3.2 Design of peptidomimetics by manipulation of the amino acids,

modification of the peptide backbone, incorporating conformational

constraints locally or globally, α-helix, β-sheet, β-and γ-turn mimetics

3.3 Examples of peptidomimetics for some enzymes and receptors like ACE,

CCK, bradykinin

4.0 Antisense therapeutic agents 6

4.1 History and principles

4.2 Design of antisense oligonucleotides and small interfering RNAs

(siRNAs) with some examples

5.0 Molecular Biology, Genetic engineering and Biotechnology in

production of biologicals as drugs.

7

Total 45

Books

1. The Organic Chemistry of Drug Design and Drug Action, Silverman R. B., Academic Press.

2. Textbook of Drug Design and Discovery, Eds. Krogsgaard-Larsen P., Liljefors T., Madsen U.,

Taylor & Francis.

3. Medicinal Chemistry: An Introduction, Thomas G, Wiley.

4. Peptide and Protein Design for Biopharmaceutical Applications, Ed Jensen K. J., Ch. 3

Aspects of Peptidomimetics by Maes V.,Tourwé D., John Wiley & Sons, Ltd, Chichester,

UK.

5. Comprehensive Medicinal Chemistry, Series Ed., Hansch C., Pergamon Press.

6. Burgers Medicinal Chemistry, Drug Discovery and Development, Wiley.

Course No. MPMC 210 Title of the Course: Basic Molecular Biology Credits 3


Hours

1.0 The beginnings of molecular biology 1

2.0 DNA Structure and Role of DNA 12

2.1 Organization of the genome, building from nucleotides to chromatin

2.2 The genetic code and its relationship to protein structure

2.3 DNA replication, Telomere maintenance, mechanisms of DNA repair, DNA

recombination

3.0 The versatility of RNA 16

3.1 Transcription and translation in prokaryotes; Transcription and translation in

eukaryotes

3.2 Epigenetics and monoallelic gene expression

3.3 RNA processing and post-transcriptional gene regulation

3.4 Mechanisms of translation

4.0 Genetically modified organisms: Use in basic and applied research 14

4.1 Recombinant DNA technology, molecular cloning, & some tools for analyzing

gene expression

4.2 Genome analysis: DNA typing; Genomics and beyond; Medical molecular

biology: applications in Cancer and Gene therapy; Genes and behaviour

5.0 Plant tissue culture and animal cell culture 2

Total 45

Books

1. Genes IX, Ed Benjamin Lewin. Oxford University Press.

2. Molecular Cell Biology, Lodish H, Berk A, Zipursky S L, Matsudaira P., Baltimore D, Darnell J,

Publisher W. H. Freeman.

3. Molecular Biology of the Cell, Alberts Publisher Garland Science.

4. Watson, J. D. Tania A. Baker, Stephen P. Bell, Alexander Gann, Michael Levine, Richard

Losick, Molecular Biology of the Gene, Benjamin Cummings; 6th Edition, 2007.

5. Molecular Biology in Medicinal Chemistry, Dingemann Th, Steinhilber D and Folkers G,

Wiley-VCH, Germany

6. Basic Principles of Gene Manipulation, Primrose SB, Twyman RM and Old RW, Blackwell.

7. Molecular Biology and biotechnology, Walker JM and Rapley R, Royal Society of Chemistry

Practical Courses

Course No. MPMC 210P Title of the Course: Basic Molecular Biology Credits 3


Hours

1.0 Experiments with cells – homogenization of the tissue, centrifugation,

marker enzyme assays, microscopy and microphotography of cells

2.0 Quantitative assays - enzyme assays, RIA, ELISA, assays for DNA, RNA &

proteins

3.0 Fractionation of proteins – salting out, , electrophoretic separation, gel

filtration, affinity based chromatography, ion-exchange, HPLC, SDS-

PAGE.

4.0 Enzymology – purification of enzyme & study of enzyme kinetics

5.0 Experiments on DNA –genomic and plasmid DNA isolation, cloning,

restriction enzyme digestion, ligation, transformation, electrophoresis,

PCR, real-time PCR.

6.0 Southern blotting, Western blotting and Northern blotting

7.0 Absorption & fluorescence spectroscopy

8.0 Plant tissue culture

9.0 Animal cell culture

Total 60

Books

1. Molecular Cloning- A Laboratory Manual. J. Sambrook, E.F. Fritsch and T. Maniatis.

Cold Spring, Harbor Laboratory Press.

2. Wilson, K. and Walker, J., Principles and Techniques of Practical Biochemistry and

Molecular Biology, 7th Edition, Cambridge Univ. Press, 2010

3. Christian, G. D., Analytical Chemistry, John Wiley & Sons (Asia) Pvt. Ltd., 2004

4. R. Ian Freshney, Culture of Animal Cells: A Manual of Basic Technique and Specialized

Applications, John Wiley and Sons, 2010.

5. C. Neal Stewart, Jr., Plant Biotechnology and Genetics: Principles, Techniques and

Applications, 2008

Elective Subjects

Course No: MPMC 221 Title of the Course: Drug Metabolism Credits 3


Hours

1.0 Introduction to xenobiotic/drug metabolism and its relation to other defence

systems (Physical barriers, excretion, immune system).

4

1.1 Types of reactions (I and II), consequences of drug metabolism (DM)

[inactivation, bioactivation, prodrugs], organs of DM, localization of drug

metabolizing enzymes, factors affecting drug metabolism.

2.0 Cytochrome P450s: Introduction to the family of enzymes, their classification

and nomenclature.

14

2.1 CYP450 catalytic cycle, different types of reactions catalyzed by CYP450s and

the mechanisms of catalysis.

2.2 Human CYP450s involved in DM, their distribution and properties, typical

substrates, specific probe substrates, specific inhibitors, induction of CYPs and

specific inducers

3.0 Discussion of glucuronosyltransferases, sulfotransferases, glutathione S-

transferases, N-acetyl transferases, and FMO [on lines similar to that specified

for CYPs as listed above].

14

4.0 Introduction to methods for studying DM. Discussion of in vitro and in vivo

tools, along with their advantages and limitations {recombinant enzymes,

subcellular fractions, hepatocytes, liver slices, perfused liver and whole animal

studies}.

5

5.0 Discussion of types of DM studies – metabolic stability, cross species

comparisons, metabolite profiling and identification, reaction phenotyping,

CYP inhibition and CYP induction studies.

6

6.0 Introduction to in silico drug metabolite predictions and associated

algorithms.

2

Total 45

Books

1. Comprehensive Medicinal Chemistry, Series Ed., Hansch C., Pergamon Press.

2. Wilson and Gisvold’s, Textbook of Organic Medicinal and Pharmaceutical Chemistry, Lippincott-

Raven

3. Foye’s Principles of Medicinal Chemistry, Lippincott Williams and Wilkins.

4. Drug Metabolizing Enzymes-Cytochrome P450 and Other Drug Metabolizing Enzymes in Drug

Discovery and Development, Lee JS, Obach SR and Fisher MB, Marcel Dekker, Fontis India, 2003

5. Pharmaceutical Profiling in Drug Discovery for Lead Selection, Borchardt RT, Kerns EH, Lipinski CA,

Thakker DR and Wang B, AAPS Press, 2004

6. Drug Metabolism – Current Concepts, Ionescu C and Caira MR, Springer International Edition

7. Handbook of Drug Metabolism, Woolf TF, Marcel Dekker, 1999.

Course No: MPMC 222 Title of the Course: Pharmacokinetics Credits 3


Hours

1.0 Introduction to pharmacokinetics and its utility in drug design and dosage regimen

design. Definitions of absorption, distribution, metabolism, excretion, elimination.

Different approaches for determination of pharmacokinetics of drugs – non-

compartmental, physiological, and compartmental modeling. Assumptions involved in

the evolution of single and multi-compartment models.

6

2.0 Discussion (including mathematical description and equations) of the pharmacokinetics

of drugs showing one compartment pharmacokinetics following intravenous bolus

dosing[blood/plasma/urine sampling]

20


of drugs showing one compartment pharmacokinetics following intravenous multiple

bolus dosing[blood/plasma]


of drugs showing one compartment pharmacokinetics following intravenous constant

infusion dosing [blood/plasma].


of drugs showing one compartment pharmacokinetics following extravascular bolus

dosing [blood/plasma]. Discussion of the concepts of bioavailability (absolute and

relative) and bioequivalence.


of drugs showing one compartment pharmacokinetics following extravascular multiple

bolus dosing [ blood/plasma].

2.5 Discussion of approaches to solve problems related to the analysis of pharmacokinetic

study data obtained after different types of dosing. Discussion of approaches to

problem solving involving data from bioavailability and bioequivalence studies.

Discussion of approaches to dosage regimen design

3.0 Discussion of the processes of absorption, distribution and elimination with respect to

how these processes impact the values of rate constants for

absorption/distribution/elimination and the values of bioavailability, volume of

distribution and clearance.

10

4.0 Introduction to drug transporters and their impact on the pharmacokinetics of drugs

and pharmacokinetic drug-drug interactions.

4

5.0 Brief introduction to the concept of dose- and time-dependent pharmacokinetics [non-

linear pharmacokinetics] and their impact on drug development and clinical use.

5

Total 45

Books

1. Clinical Pharmacokinetics and Pharmacodynamics-Concepts and Applications, Rowland M

and Tozer TN, Walters Kluwer – Lippincott Williams and Wilkins.

2. Applied Biopharmaeutics and Pharmacokinetics, Shargel L and Yu ABC, Appleton and

Lange, International Edition

3. Handbook of Basic Pharmacokinetics including clinical applications, Ritschel WA and

Kearns GL, APhA,

4. Basic Pharmacokinetics, Jambhekar SS and Breen PJ, Pharmaceutical Press.

5. Biopharmaceutics and Pharmacokinetics, Venkateshwarlu V, Pharma Book Syndicate

Course No. MPMC 223 Title of the Course: Rational Drug Design Credits 3


Hours

1.0 Molecular Mechanics and the forcefield. General form of a generic

force field, force field parametrization.

5

2.0 Energy minimization 5

2.1 Steepest descents, conjugate gradients, Newton Raphson method,

advantages and limitations of each method

3.0 Conformational analysis 10

3.1 Systematic search, Monte Carlo simulations, Molecular dynamics

simulations, distance geometry, strengths and limitations of each

method

4.0 Docking 6

4.1 Docking by energy minimization, superimposition, molecular dynamics,

Metropolis Monte Carlo, genetic algorithms, build-up approach.

Different types of scoring function, e.gs of successful application of

docking.

5.0 de novo ligand design 6

5.1 Classes of de novo ligand design – active site analysis methods, whole-

molecule methods, connection methods, random connection and

disconnection methods, e.gs of successful application of denovo ligand

design

5.2 Fragment based drug design

6.0 Pharmacophore modelling 6

6.1 Techniques of developing a pharmacophore map covering both ligand

based and receptor based approaches, incorporating additional

geometric features into a 3D pharmacophore, use of a pharmacophore

model in drug design, successful e.g. of pharmacophore maps in drug

design.

7.0 Virtual Screening based on similarity, docking, pharmacophore maps

and filters for drug-likeness and ADME

3

8.0 3D-QSAR 4

8.1 CoMFA and CoMSIA. Mention of other 3D-QSAR techniques and

introduction to the 4th

, 5th

and 6th

dimension in QSAR.

Total 45

Books

1. Molecular Modelling – Principles and Applications, Leach A. R., Prentice Hall.

2. Practical Application of Computer-Aided Drug Design, Ed. Charifson P., Marcel

Dekker Inc.

3. 3D QSAR in Drug Design: Theory, Methods and Applications, Ed. Kubinyi H., Ledien

ESCOM.

4. Molecular Modeling and Simulation -An Interdisciplinary Guide, Schlick T., Springer.

Course No. MPMC 224 Title of the Course: Advanced Biochemistry Credits 3


Hours

1.0 Proteins 15

1.1 Structure – primary, secondary, tertiary, quaternary; motifs, structural

and functional domains, protein families and macromolecular

assemblies

1.2 Mechanisms for regulating protein function: Protein-protein

interactions, interaction with ligands; Ca2+

and GTP as modulators,

cyclic phosphorylation and dephosphorylation, proteolytic cleavage.

1.3 Purification and characterisation of proteins: electrophoresis,

ultracentrifugation and liquid chromatography, use of biological assays,

use of radioisotopes; MS, X-ray crystallography, NMR and homology

modelling to determine structures; amino acid analysis; cleavage of

peptides; protein sequencing.

1.4 Protein biosynthesis: translation machinery in prokaryotic and

eukaryotic systems; comparison of similarities and differences, drug

affecting protein biosynthesis and protein function

2.0 DNA and nucleic acids 15

2.1 DNA, RNA structure, nomenclature, double helix, conformations, higher

order packing and architecture of DNA, transcription and replication of

DNA – mechanisms in prokaryotic and eukaryotic systems, DNA repair

mechanisms, drug affecting nucleotide biosynthesis, RNA and DNA

biosynthesis and RNA and DNA function

3.0 Carbohydrates 8

3.1 Mono, di and polysaccharides and their nomenclature,

stereochemistry, types of linkages; conjugates of carbohydrates with

other molecules – glycoproteins, glycolipids, proteoglycans,

lipopolysaccharides and their biological roles

4.0 Lipids 7

4.1 Classification, nomenclature, stereochemistry, storage lipids,

membrane lipids, lipids as secondary messengers and cofactors,

biological role of lipids, drug affecting lipid metabolism.

Total 45

Books

1. Principles of Biochemistry, Lehninger, Nelson D.L., C.B.S Publishers, New Delhi.

2. Biochemistry, Stryer L, W. H. Freyment& Co., New York.

3. Molecular Cell Biology, Lodish H, Darneu J, Scientific American Books, N.Y.

4. Biochemistry- The chemical reactions of living cells, Vol 1 &2, Metzler DE, Elsevier

Academic Press.

5. Biochemistry, Berg JM, Tymoczko JL and Stryer L, WH Freeman and Company and

Sumanas Inc.

6. Biomacromolecules- Introduction to structure, function and informatics, Stan Tsai C,

Wiley-Liss

7. Protein: Structure and Molecular properties, Thomas E Creighton, W. H. Freeman.

8. Physical Biochemistry- Principles and applications, Sheehan D, Wiley-Blackwell

Course No: MPMC 251 Title of the Course: Research Seminar 2 -Literature Review and

proposed research plan Credits: 3

The students will do a literature survey for the research work that is to be carried out in

Semesters III and IV and present a Seminar which should cover aspects of literature report,

plan of research work, methodology timelines, and expected outcome of the work before a

committee that will constitute the Research Work, Head of the Department and the other

faculty of the Dept. of Pharmaceutical and Medicinal Chemistry.

Course No: MPMC 252 Title of the Course: Minor Research Project Credits: 3

The students will do a Minor Research Project in an area of their choice and will not be

restricted to the Department. He/She will be evaluated by their respective Minor Research

Project Guide for satisfactory completion of the Minor Research Project.

Semester III

Course No MPMC 300. Title of the Course: Research Methodology Credits 3


Hours

1.0 Objectives and purposes of research, type of research (educational,

clinical, experimental, basic , applied, patent oriented research)

2

2.0 Literature Survey 3

2.1 Use of the library, books and journals, Medline, Internet, obtaining

patents and reprints of articles

3.0 Selecting a problem and preparing a research proposal for different

types of research mentioned in Unit 1.0

4

4.0 Methods and tools used in Research 10

4.1 Qualitative and quantitative studies, simple data organization,

descriptive data analysis, limitations and sources of errors, inquiries in

form of questionnaires, opinions or by interview, statistical analysis of

data including variance, standard deviation, standard error, mean,

student’s “t” test and Anova, correlation of data and its interpretation,

computer data analysis.

5.0 Documentation 5

5.1 Techniques and importance of documentation, uses of computer

packages in documentation

6.0 Scientific writing and reporting 5

6.1 Different types of research papers, title and author names, abstract,

key words, methodology,

7.0 Scientific Presentation 5

7.1 Importance, types, different skills, content, format of model,

introduction and ending, skills for oral presentation and types of visual

aids, questionnaire

8.0 Protection of Patents and trademarks, designs and copyrights 4

8.1 The patent system in India, present status of Intellectual Property

Rights (IPR), product patent, process patent, requirements and

preparation of patent proposals, registration of patents in foreign

countries

9.0 Cost Analysis of the project 5

9.1 Cost incurred on raw materials, cost incurred on procedure, cost

incurred on instrumentation, cost incurred on preclinical and/or clinical

studies, commercialization of patents

10.0 Industry-Institute Interaction, industry projects – feasibility studies 2

Total 45

Books

1. Research in Education, Best J. W., Khan J. V., Prentice Hall of India Pvt. Ltd.

2. Presentation Skills, Hatton, M., Indian Society for Technical Education.

3. Thesis and Assignment Writing, Jonathan A., Berry H D., Wiley Eastern Ltd.,

Bangalore.

4. Writing a Technical Paper, Menzel D. H., McGraw Hill Book Co., Inc.

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