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M. Pharm. Pharmaceutical Chemistry Syllabus

Semester - I

Theory Papers:

3. Spectroscopic Identification of Organic Compounds
Practicals:

1. Advanced Organic Chemistry -1 Practicals 2. Advanced medicinal Chemistry -1 Practicals
Semester - II
Theory Papers:

4. Chromatographic Separation technology
Practicals:

1. Chemistry of Natural Products Practicals 2. Advanced Medicinal Chemistry - 2 Practicals Pharmaceutical Chemistry
Semester - I
Paper 1: Advanced Organic Chemistry - 1
1. Nucleophilic aliphatic substitution: SN1 and SN2 reactions; mechanism and
kinetics; structure and reactivity; stereochemistry; SN1 Vs SN2; role of solvent; substitution Vs elimination; necleophilic substitution - alkyl halides Vs alcohols; SN1 and rearrangement; stability of carbocations.
2. Electrophilic aromatic substitution: reactions; mechanism; proof for the
mechanism; sulfonation - a reversible reaction; theory of reactivity; theory or orientation; orientation and synthesis. 3. Elimination reactions: E1 and E2 mechanisms of alkyl halides and alcohols;
evidence; E1 Vs E2; elimination Vs substitution; 1,1 and 1,2- elimination; E1CB; Saytzeff's rule; Hofmann rule/elimination; stereochemistry of E2 reactions; elimination from alicyclic compounds. 4. Heterocylic chemistry: Structures of heterocylic compounds; aromatic and
nonaromatic heterocylces; nomenclature; ring sysnthesis; reaction types most frequently used in heterocylic ring sysnthesis; typical reactant combinations; cylcization reactions; displacement at saturated carbon, intramolecular nucleophilic addition to carbonyl groups, intramolecular addition of nucleophiles to other double bonds, cyclization on to triple bonds, radical cyclization, carbine and nitrene cyclization; electrocylic processes in heterocyclic ring synthesis; cycloaddition reactions; 1,3-dipolar cycloaddition, hetero-Diels-Alder reactions, (2+2) cycloaddition. 5. Heterocylic chemistry: reactivity of aromatic heterocycles; electrophilic addition
at nitrogen; electrophilic, nucleophilic and radical susbstitution at carbon; deprotonation of N-hydrogen; organometallic derivatives; palladium catalyzed reactions; oxidation and reduction of heterocyclic rings. 6. Five-membered ring compounds with one heteroatom:Pyrroles, Furans and
Thiophenes; Aromaticity; two synthetic methods for each class; reactions; electrophillic substitution; reactions with acids, carbenes, nitrenes; oxidizing and reducing agents; Diels-Alder reaction; photochemical reactions; alkylation of pyroles; metalation of furans; reactions of thiophenes with nucleophiles. Books Recommended:
1. Organic chemistry - Morrison and Boyd (with study gudie), 11th edition
2. Reaction Mechanisms - Peter Sykes
3. Heterocyclic Chemistry - Joule, Mills and Smith
4. Heterocyclic Chemistry - Thomas Gilchrist.
5. Heterocyclic Chemistry - Raj K. Bansal
6. Text Book of organic chemistry - Clayton, Greeves, Warren and Wothers.
Semester - II
Paper 2: Advanced Medicinal Chemistry - 1

1. Genesis of new drugs:
i) A brief review of the following topics: sources of new drugs; leads from natural
products; molecular modifications; random screening; high throught put screening;
insilico screening; structural features and pharmacological acivity; prodrugs; soft drugs;
isosterism.
ii) A brief account of drug discovery by recombinant DNA technology.
2. Drug Design:
i) QSAR in drug design:
a) Phisical properties related to potency.
b) Calculation, measurements and significance of various parameter used in QSAR -
(Lipophilicity, steric, Electronic effects). c) applications of Hansch Analysis
ii) Computers in drug design: Introduction; computer graphics and molecular
visualization; computational chemistry overview, force fielf methods; geometry
optimization; conformational searching; molecular dynamics simulations; quantum
mechanics; structure based drug design and Pharmacophore perception, predictive
ADME.
3. A study of:
i) β-adrenergic blockers ii) ACE inhibitors iii) synthesis of propranolol, hydralazine,
minoxidil, captopril, lisinopril
4. A Study of
i) H1-antagonists ii) H2-antagonists iii) Gastric-proton pump inhibitors iv) Synthesis of
levocitrizine, ranitidine, omeprazole
5. A study of:
i) Analgesics (non-opioid) and antipyretics
ii) Non-steroidal anti-inflammatory agents
iii) sysnthesis of paracetamol, ibuprofen, aceclfenac
6. A study of:
i) Anti-cancer agents ii) anti Viral agents iii) Immunosupressants and immunostimulatns
iv) Synthesis of chlorambucil, methotrexate, stauvudine
NOTE: "A study of" includes an account of their origin and development, classification,
structures, mechanism of action, SAR, uses and toxicity.
Books Recommended:
1. Wilson and Gisvold's text book of pharmaceutical organic medicinal chemistry 2. Foye's principles of medicinal chemistry 3. Burger's medicinal chemistry and drug discovery 4. Organic chemistry of synthetic drugs - Lednier Paper 3: Spectroscopic identification of organic compounds

A brief account of the basic principles involved & instrumentation, and a detailed study of applications of the following spectroscopic techniques in the determination of structure of the following classes of compounds with the help of simple examples: i) Alkanes ii) Cycloalkanes iii) Alkenes iv) Aldehydes and ketones v) Alcohols vi) Carboxylic acids vii) Phenols viii) Amines ix) Simple Heterocyclic Compounds 1. UV & IR spectroscopy 2. 1H NMR (proton NMR) 3. 13C NMR 4. Mass spectrometry 5. A brief account of the two dimensional NMR techniques like DEPT, COSY, 6. Problems and their solution - simple problems dealing with structure 1. The aim of this course is to train the student in the spectroscopic identification of organic compounds. Therefore, the emphasis while teaching the subject should be on the applications of the techniques. 2. The theory behind 2D-NMR techniques shall not be taught 3. The use of 2D-NMR techniques to confirm the structural features/assignments of the compounds alone will be emphasized, preferably by giving simple examples. 4. Unit-6: Problems given in Morrison & Boyd and Silverstein & Basler to be
Books Recommended:

1. Organic chemistry - Morrison & Boyd-11th edition along with the study guide. 2. Spectroscopic methods of identification of organic compounds - Silverstein and 3. Organic spectroscopy - William kemp 4. Instrumental methods of analysis - John Dyer. 5. Structure elucidation by modern NMR, a work book - Duddeck, Detrich and Toth 6. Solving problems with NMR spectroscopy-Atta-Ur-Rahman and Muhammad Paper 4: Screening methods in Pharmacology

Principles and techniques involved in the Pharmacological screening of:
1. Analgesic, anti-inflammatory, antipyretic and antiulcer drugs.
2. Antidiabetic and cardiotonic, antiarrhythmic and antihypertensive drugs.
3. Hepatoprotective and immunomodulatory drugs.
4. a) Screening for free radical scavenging and anti-oxidant activities.
b) Enzyme inhibition studies - Inhibition of COX-1, COX-2 and 5-LOX 5. a) Screening of cytotoxicity
b) Screening for antimicrobial activity
c) Acute toxicity studies
6. Statistical analysis of data, methods of precision, accuracy, fiducial limits,
regression analysis, standard error, tests for significance - chisquare test, students
T test, ANOVA. Important of tests of significance in pharmaceutical/biological
experiments.
Books recommended:

1. Screening methods in pharmacology - Robert A. Turner. 2. Drug Evaluation - Vogel. 3. Evaluation of Drug Activities - Lawrence and Bachrach. 4. Methods in Pharmacology - Swarbrick. 5. Pharmacopoeias. Semester - 1
Paper 1: Advanced Organic Chemistry - 1 Practicals

Some of the following experiments to be taught.
1. Basic Techniques:
a) Calibration of thermometer and finding melting point, mixed melting point and boiling
point.
b) Purification and drying of organic solvents
c) Crystallization
d) Distillation, Fractional Distillation, Distillation under reduced pressure
2. Separation and identification of organic compounds from binary mixtures: Solid-
solid, solid-liquid and liquid-liquid - atleast one mixture of each category to be done.
3. Synthesis of some of the following heterocyclic compounds:
a) Quinoline b) benzimidazole/derivative c) flavone/chromone d) indole/derivative e)
phenothiazine f) oxazole/oxazolone g) benzoxazole h) 3,5 dimethylisoxazole
4. Some of the following reactions:
1. Beckmann rearrangement 2) Fries rearrangement 3) Acetylation, methylation
4) Metal/acid reductions 5) Oppenauer oxidation 6) Friedel-Craafts alkylation &
Acylation 7) Nitration using different reagents
Books Recommended:

Practical Organic Chemistry - Vogel.
Paper 2: Advanced Medicinal Chemistry -1 Practicals

1. Synthesis, purification and identification some of the following drugs. 2. a) Sulfanilmide b) Uracil c) Phenytoin d) Ibuprofen e) para-Amino salicylic acid (PAS) f) Paracetamol g) Atenolol (h) proranolol. 3. Screening for the following activities a) CNS - Rota rod experiment Catatonia testing b) Experiments on isolated tissues - Testing for anti-histaminic and anti- a) Spectra to be recorded for some compounds and analyzed. b) Analysis of pre-recorded spectra. Semester - II
Paper 1: Advances Organic Chemistry - 2

1. Strategies in organic synthesis: Introduction; target selection; disconnection
approach; functional group intervoncersions; synthons; reagents; retrosyntheis, chemioselectivity, regioselectivity; linear synthesis and concergent sysnthesis.
2. Strategies in organic sysnthesis: one group disconnections; two group
disconnections; strategic bonds; disconnection of strategic bonds in carbocyclic and heterocyclic rings; biomimetic approach; retro mass spectral fragmentation - case studies of (+) Disparlure, retronecine and longifoline. 3. Chiral drug synthesis: Introduction to chiral drugs; importance of
stereochemistry in drug action; concepts of eutomer; distomer and eudesmic ratio, stereospecific and stereoselective synthesis; synthesis of chiral drugs like ibuprofen, propranolol, ramipril, levofloxacin. 4. Modern synthetic methods:
a)Green Synthesis: Inttroduction; Green reagents; green catalysts; ionic solvents; phase transfer catalysis in green synthesis; application of phase transfer catalysts in green synthesis of heterocyclic compounds: Williamson's synthesis, Wittig reaction. b) Microwave assisted synthesis: Introduction; microwave reactions in water (Hofmann elimination, hydrolysis and oxidation); microwave reactions in organic solvents; solid state reactions; advantages of microwave technique. 5. Six-membered heterocyclic ring compounds with one heteroatom: Pyridines:
nomenclature; physical and spectroscopic properties; tautomerism; synthetic methods; chemical reactions - with acids, electrophilic and nucleophilic substitution, Diels-Alder reactions, quaternization, reaction with oxidizing and reducing agents; hetaryne formation; ring opening reactions; reactions with free radicals; photochemical reactions; the Claisen rearrangement; derivatives of pyridine - alkyl and aryl pryidinesl halopyridines, aminopyridines, pyridine N-oxide, hydroxypyridines, pyridine aldhydes and ketones.
6. Synthesis of Heterocyclic compounds: Two methods of synthesis of the
following heterocylic compounds or their derivatives; a) quinolines b) isoquinolines c) indoles d) pridazines e) pyrimidines f) pyrazines g) thiazoles h) thiazines h) imidazoles i) benzimidazoles j) oxazoles
Books recommended:
• Organic synthesis-new techniques - VK Ahluwalia & Renu Agarwal • Top Drugs and Top Synthetic routes - John Saunder • Theory and Practice of Green Chemistry - Paul T Anastas and John C.Warner. • New Trends in Green Chemistry - VK Ahluwalia & M Kidwai • Chiro Technology - Roger A. Sheldon • Heterocylcic Chemistry - Raj K Bansal • Heterocyclic Chemistry - Thomas L. Gilchrist • Heterocyclic Chemistry - JA Joule, K Mills & GF Smith • Organic Chemistry of Synthetic drugs - Lednicer.
Semester - II

Paper 2: Advanced Medicinal Chemistry - 2

1. Psychopharmacological agents: Biochemical basis of mental disorders;
abnormal protein factors; endogenous amines and related substances; faulty energy metabolism; genetic disorders and nutritional disorders; phenothiazines - chemistry; synthesis. Screening methods; pharmacological actions; SAR; mechanism of action; uses; toxicity; ring analogues of phenothiazines; fluorobutyrophenones; Development of atypical antipsychotics cloyepire synthesis of chlorpromazine, prochlorperazine, fluphenazine, haloperidol.
2. Anxiolytics, sedatives and hypnotics: Benzodiazepines and related compounds;
barbiturates; other classes; mechanism of acition, SAR; uses and toxicity Synthesis of Chlordiazepoxide, diazepam, alprazolam, Phenobarbital, meprobamate. 3. Antidepressants: MAO inhibitors; tricylic antidepressants; SAR; mechanism of
action; uses; toxicity other classes like: selective serotonin reuptake inhibitors, selective 5-HT and NE reuptake inhibitors; selective serotoninergic reuptake inhibitors and 5-HT2A antagonists; 5-HT1A agonists and partial agonists and α2-antagonists. Syntheis of tranycypromine, amitriptyline, fluoxetine, buspirone. 4. Antiepileptics & CNS stimulants:
a) Antiepileptics: Screening methods; classification of epilepsies; symptoms; drugs used; classification; structural feactuers common to drugs; SAR; mechanism of action; toxicity and uses; synthesis of diphenylhydantion, carbamazepine, sodium valproate. b) CMS stimulants: an account of the drugs with CNS stimulant activity; 5. Diuretics: anatomy and physiology of nephron; classification of diuretics based
on site of action; carbonic anhydrase inhibitors; thiazide and thiazide like diuretics; loop and potassium sparing diuretics; miscellanous diuretics emerging developments in the use of diuretics to treat hypertension and congestive heart failure.
6. A Study of: a) Anthihyperlipidemic agents
b) phosphodiesterase inhibitors c) Quinolone antibacterial agents. Books Recommended:
1. Wilson and Gisvold's text book of pharmaceutical organic medicinal chemistry.
2. Foye's principles of medicinal chemistry.
3. Burger's text book of medicinal chemistry
4. Organic chemistry of synthetic drugs - Lednicer.

Paper 3: Chemistry of Natural Products:

1. Alkaloids :
a) Alkaloids of opium: Structure of morphine; peripheral groups; SAR;
relative potencies; development of morphine analogues; opioid receptors endorphins and enkephalins; antitussives; anti-diarrhoeals; morphine antagonists; b) Alkaloids of ergot: historical background; classification; structures; semi-
synthetic derivatives; therapeutic uses; toxicity. c) Source, structure, mechanism of action, use and toxicity of: quinine,
quinidine, atropine, hyoscyamine, hyoscine, reserpine, papaverine. 2. Anticancer agents of natural origin:
a) Alkaloids of Vinca rosea: Vincristine & Vinblastine - Structures and
SAR; Semisynthetic derivatives; Mechanism of Action; Uses and Toxicity. b) Sources and structures of podophyllotoxin, taxol and camptothecin; semisynthetic derivatives; mechanism of action; uses and toxicity. c) Anticancer antibiotics: Source; structures; description of the structural
features; mechanism of action; SAR and uses of the following antibiotics; dactinomycin; daunorubicin; doxorubicin; their daunomycinol; adriamycinol; their semi-synthetic derivatives- 4'-deoxy and 4' epidoxorubicins; noglamycin and menogaril; mithramycin; mitomycins; streptozocin. d) Anticancer agents from marine organisms - bryostatin, dolastatin etc. 3. Steroids:
a) Nomenclature; stereochemistry; numbering; new insights on steroid receptors; chemical and physical properties of steroids; changes to modify pharmacokinetic properties of steroids. b) Sources and structures of cholesterol, ergosterol, stigmasterol and diosgenin. History of development of steroid industry. Marker's synthesis. c) Steroidal anti-inflammatory agents; structures; SAR; uses and toxicity. 4. Steroidal Hormonal Drugs:
a) Steroidal antifertility agents: estrogens; pregnane progestins; development of 19-norandrostanes; structures; mechanism of actions; regimen; toxicity. b) Anabolic Steroids: rationale for development; structures; uses; limitations. c) Steroids in the treatment of cancers; estrogens; antiestrogens; aromatase inhibitors; progestins; progestin antagonists; androgens and anabolic steroids; antiandrogens; 5 α-reductase inhibitors; gonadotropin inhibitors, glucocorticoids. 5. Cephalosporins: Historical background; classification; structures; numbering the
ring system; nomenclature; degradation; spectrum of activity; SAR; β-lactamase resistance; antipseudomonal cephalosporins; mechanism of action; uses; toxicity; development of new cephalosporins - recent advances; prodrugs in cephalosporins; pencillins Vs cephalsosporins - a comparative account of the structural features and biological activity; β-lactamase inhibitors; mechanism of β-lactamase inhibition; monobactams.
6. Structure elucidation: of the following compounds by spectroscopic techniques
like UV, IR, MS, NMR (1H, 13C), including 2D-NMR.
Note: In teaching unit - 6 the exact shift values need not be given. It is sufficient if the
student is taught how many peaks appear for the compound in the NMR and
approximately, in which region, how the 2D-NMR spectra like DEPT look like; which
protons interact to give the COSY; and how the long range spectra will help to confirm
the structure.
Books Recommended:

1. Wilson and Gisvold's text book of pharmaceutical organic medicinal chemistry. 2. Foye's principles of medicinal chemistry. 3. Burger's medicinal chemistry and drug discovery. Paper 4: Chromatographic separation technology

Theory and instrumentation of the following techniques for the separation of organic
compounds.
1. TLC and HPTLC 2. Coloumns chromatography (open) and its modifications like flash, vacuum liquid and medium pressure chromatographies, Gel Permeation technique. 3. HPLC 4. GLC 5. Electrophoresis (Gel and Paper) 6. A brief account of: a) Paper chromatography b) Super Critical chromatography c) Chiral Separations d) Circular counter current chromatography (CCCC) e) Ion Exchange methods a) The various column materials used in these techniques. b) The detectors in the case of techniques like HPLC, HPTLC and GLC. c) The relative advantages and limitations of the techniques. 1. Instrumental methods of analysis - Willard, Merritt, Dean and Settle. 2. Instrumental methods of chemical analysis - Gurudeep R. Chatwal and Sham K. 3. TLC - Egon Stahl. 4. TLC - Kirchner. Semester - II
Paper 1: Chemisty of Natural Products - Practicals

1. Isolation and purification of some of the following natural products. a) Piperine from black pepper b) Strychnine and Brucine from Strychnos nuxvomica seeds c) Caffeine from Tea Powder d) Curcumin from Turmeric e) Bixin from Bixa orellana seeds f) Diosgenin from Diascoria tubers g) Sennosides from Senna leaves h) Embelin from Emblica ribes fruits 2. The use of column, flash and vacuum liquid chrmatographies for isolating some of the above mentioned phytoconstituents. 3. Identification of alkaloids in mixture by TLC. 4. Preparative TLC for separation and isolation 5. Identification of phytoconstituents like alkaloids, steroids, flavanoids etc in plant 6. Separation (of sugars/amino acids) by paper chromatography. 7. Separation of compounds by HPLC 8. Analysis of recorded spectra of some simple organic compounds. 9. Tests to detect alkaloids, steroids, flavanoids and their glycosides.
Books Recommended:
1. Natural products, a laboratory guide - Rephael Ikan. 2. Laboratory hand book for the fraction of natural extracts - Peter J. Houghton &
Paper 2: Advanced Medicinal Chemistry - 2 Practicals

1. Synthesis, purification and identification of some of the following drugs;
a) Dapsone b) Benzocaine c) Hydralazine d) Imipramine e) Sufadiazine 2. Synthesis using microwave oven: one experiment to be conducted 3. Screening for the following activities: a) Analgesic activity b) Anti inflammatory activity c) Acute toxicity studies d) Antibacterial and antifungal activity e) Free radical scavenging and a) Spectra to be recorded for some compounds and analyzed. b) Analysis of pre-recorded spectra 5. Impurity profiling for one or two samples.

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