ࡱ> 24/01q`  bjbjqPqP 4::n%4448l=2"eee8::::::$oh^%@e^{ճճճ8ճ8ճճX | 1RN4F 4 0="uu u @e9Nճ (eee^^qdeee=d[0c10c JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY ANANTAPUR Course Structure and Syllabus for M. Pharm- Pharmaceutical Chemistry for affiliated and constituent Pharmacy Colleges 2009-10 I YEAR I SEMESTER SubjectHours/ WeekModern Pharmaceutical Analysis4Bio-Statistics, Intellectual Property Rights& Regulatory Affairs 4Advanced Pharmaceutical Organic Chemistry 14Advanced Medicinal Chemistry I 4Modern Pharmaceutical Analysis Practical 16Advanced Pharmaceutical Chemistry Practical- I 6Mini-project- I3 I YEAR II SEMESTER SubjectHours/ WeekDrug Design 4Advanced Pharmaceutical Organic Chemistry II 4Advanced Medicinal Chemistry II4Advanced Chemistry of Natural Products4Advanced Medicinal Chemistry Practical6Advanced Natural Products Chemistry Practical 6Mini-project- II3 II YEAR (III & IV Semesters) SUBJECTSSeminarProject work JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY ANANTAPUR M.Pharm Pharmaceutical Chemistry I year I semester MODERN PHARMACEUTICAL ANALYSIS 1. UV-VISIBLE SPECTROSCOPY: Brief review of electromagnetic spectrum, UV-Visual range, energy, wavelength and color relationships. Interaction of electromagnetic radiation (UV-visible) with matter and its effects. Chromophores and their interactions with E.M.R. Absorption spectra of organic compounds and complexes illustrating the phenomenon and its utilization in qualitative and quantitative studies of drugs. Shifts and their interpretation (including solvent effects). Empirical correlation of structure with absorption phenomena (Woodwards rules etc) Quantitative estimations, Modern instrumentation. a) INFRARED SPECTROSCOPY: Nature of Infra-red radiation. Interaction of I.R radiation with I.R molecules and effects on bonds. Molecular Infrared Spectra. Brief outline of classical I.R instrumentation and practical details of obtaining spectra, including sample preparation for spectroscopy, quantitative interpretation of I.R spectroscopy including FT-IR, ATR. b) OPTICAL ROTATORY DISPERSION: Fundamental principles of ORD, cotton effect curves, their characteristics and interpretation. Octant rule and its application with examples. Circular dichroism and its relation to ORD. NMR SPECTROSCOPY: Fundamental principles of NMR (Magnetic properties of nuclei, applied field and precession; absorption and transition; frequency). Chemical shifts concept: Isotopic nuclei, Reference standards: Proton magnetic spectra, their characteristics, presentation terms used in describing spectra and their interpretation (Signal No., Position, Intensity). Brief outline of instrumental arrangements and some practical details. Signal multiplicity phenomenon in high resolution PMR. Spin-spin coupling. Application of Signal split and coupling constant data to interpretation of spectra. De-coupling and shift reagent methods. Brief outline of principles of FT-NMR with reference to 13CNMR. Spin-spin and spin-lattice relaxation phenomenon. Free induction decay (FID) proton noise de-coupling signal, average time domain and frequency domain signals nuclear overhauser enhancement 13CNMR spectra, their presentation; characteristics, interpretation, examples and applications. Brief indication of application of magnetic resonance spectral data of other nuclei by modern NMR instruments. Introduction to 2-D NMR techniques. MASS SPECTROSCOPY: Basic principles and brief outline of instrumentation. Ion formation and types; molecular ion, Meta stable ions, fragmentation processes. Fragmentation patterns and fragmentation characteristics in relation to parent structure and functional groups. Relative abundances of isotopes and their contribution to characteristic peaks. Mass spectrum, its characteristics, presentation and interpretation. Chemical ionization Mass Spectroscopy. GC-MS, other recent advances in MS. Fast atom bombardment mass spectrometry. LC-MS, LC MS-MS. CHROMATOGRAPHIC TECHNIQUES: Classification of chromatographic methods based on mechanism of separation. Column chromatography, column materials, merits and demerits. Paper chromatography; techniques and applications. Thin Layer Chromatography, comparison to paper chromatography and HPLC, adsorbents for TLC. Preparation techniques, mobile phase selection, reversed phase TLC, High performance TLC detection methods, quantitative methods in TLC. Programmed multiple development techniques. GAS CHROMATOGRAPHY: Instrumentation packed and open tubular column, Column efficiency parameters, the Vandeemeter equation, Resolution, liquid stationary phase, derivatization methods of GC including acylation, perfloro acylation, alkylation and esterification. Detectors: FID, ECD, TCD, NPDA. Critical comparison of sensitivity, selectivity and field of applications of these detectors. Examples of GC applications in pharmaceutical analysis. LIQUID CHROMATOGRAPHY: Comparison of GC and HPLC, instrumentation in HPLC, analytical, preparative and microbore columns, normal and reversed phase packing materials, reverse phase HPLC, Column selection, Mobile phase selection, Efficiency parameters, resolution, detectors in HPLC refractive index, photometric and electrochemical. Comparison of sensitivity, selectivity and field of applications of these detectors. HPTLC-instrumentation and applications. ELECTROPHORESIS: Moving boundary electrophoresis, Zone electrophoresis, Iontophoresis, PAGE, Isotacophoresis and applications in pharmacy. X-ray Diffraction methods: introduction, generation of X-rays, elementary crystallography, Miller Indices, X-rays diffraction, Braggs law, X-ray powder diffraction, X-ray powder diffractometer, obtaining and interpretation of X-ray powder diffraction data. Principle, instrumentation and application of the following: Differential Scanning Colorimetry (DSC), DTA &TGA in analysis of pharmaceuticals. REFERENCES: Instrumental methods of chemical analysis by chatwal. K, anand, 5th edition. Vogels text book of quantitative chemical analysis by G.H.Jeffery, J.Bassett, J.Mendhan, R.C.Denny. Instrumental methods of analysis by Willard, Merit, Dean, Settle. Organnic spectroscopy by Y.R.Sharma. Spectrometric identification of organic compounds by silverstein, Webster. Spectroscopy by B.K.Sharma Fundamentals of analytical chemistry by Skoog Instrumental methods of analysis by Skoog. Text book of pharmaceutical analysis by S.Ravishankar. Organic spectroscopy by William kemp Spectroscopic methods in Organic chemistry by Dudley William and Ian Flemming, Tata Mc Graw Hill. JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY ANANTAPUR M.Pharm Pharmaceutical Chemistry I year I semester BIO-STATISTICS, INTELLECTUAL PROPERTY RIGHTS & REGULATORY AFFAIRS I. BIO-STATISTICS An introduction to statistics and biostatistics-collection and organization of data, graphical, pictorial presentation of data, measures of central tendency and dispersion, sampling techniques, sample size, Coefficient of variation, mean error, relative error, precision and accuracy . Tests of significance: Testing hypotheses Principles and applications of Z, t, Fratio and chi-square tests in pharmaceutical and medical research. Non-parametric tests: sign test, Wilcoxon signed rank test, Wilcoxon rank sum test, Kruskal Wallis test, run test and median tests. Design of Experiments: Principles of randomization, replication and local control; CRD, RBD, LSD their applications and analysis of data; Factorial Experiments Principles and applications; Probit analysis: Dose effect relationships, calculation of LD50, ED50.  Statistical quality control: Meaning and uses, Construction of X, R, P, p and  charts. II. INTELLECTUAL PROPERTY RIGHTS & REGULATORY AFFAIRS Patents and Intellectual Property Rights (IPR): Definition, scope, objectives, sources of patent information, patent processing and application. Patents, Copyrights, Trademarks, Salient features, international and regional agreements. GATT & WTO: GATT Historical perspective, objectives, fundamental principles, impact on developing countries. WTO objectives, scope, functions, structure, status, membership and withdrawal, dispute settlement, impact on globalization, India task and challenges, trade related aspects (TRIPS). Regulatory Affairs : Indian context requirements and guidelines of GMP, understanding of Drugs and Cosmetics Act 1940 and Rules 1945 with reference to Schedule N ,U & Y. a).Related Quality Systems: Objectives and guidelines of USFDA, WHO and ICH. Introduction to ISO series. b).Documentation: Types related to pharmaceutical industry, protocols, harmonizing formulations, development for global filings, ANDA, NDA, CTD, dealing with post approval changes SUPAC, handling and maintenance including electronic documentation. Recommended Books: KS Negi Biostatistics AITB Publishers, Delhi. Irfan Alikhan Fundamentals of Biostatistics Ukaaz Publications Khan and Khanum Biostatistics for Pharmacy Ukaaz Publications J.E, Demuth Basic statistics and Pharmaceutical applications Mercel & Dekker. Applied statistics by S.C.Gupta & V.K.Kapoor Funadamentals of mathematical statistics by S.C.Gupta & V.K.Kapoor Good Manufacturing Practices for Pharmaceuticals, S.H. Wiling, Vol. 78, Marcel Decker. Protection of Industrial Property rights, P. Das & Gokul Das Law and Drugs, Law Publications. S.N. Katju Original Laws Published By Govt. of India Laws of drugs in India, Hussain New Drug Approval Process, R.A.Guarino,Vol 100, Marcel Decker, NY fda.org,wipo.int,patentlawlinks.com, hc-sc.gc.ca,ich.org,cder.org JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY ANANTAPUR M.Pharm Pharmaceutical Chemistry I year I semester ADVANCED PHARMACEUTICAL ORGANIC CHEMISTRY I 1. Stereochemistry: Elements of symmetry, plane of symmetry, centre of symmetry, alternative axis of symmetry, simple axis of symmetry, kinds of molecules displaying optical activity. Notation, relative configuration and absolute configuration. Configurational nomenclature: D, L and R, Snomenclature. Compounds with a chiral carbon atom, compounds with other quadrivalent chiral atoms. Optical isomerism in compounds containing no chiral atom, biphenyl, allenes, compounds with exocyclic double bonds and spirans. Chirality due to helical shape, chirality caused due to restricted rotation (other types). 2. Cis / Trans, E Z isomerism resulting from double bonds, monocyclic compounds, fused ring system. Racemic modifications and methods for resolution of racemic mixtures. Asymmetric synthesis and stereoselective synthesis. 3. Reactive Intermediates: Definitions, generation, stability, structure and reactivity of free Radicals: carbocations, carbanions, carbenes, Nitrenes/Nitrenium ions. 4. Mechanisms of organic reactions: a) Substitution: Aromatic and Aliphatic nucleophilic substitution reactions (SN 1 & SN2 ), Aromatic and Aliphatic electrophilic substitution reactions, free radical substitution reactions b) Addition Reactions: Electrophilic, nucleophilic and free radical addition reactions. Addition to carbon- carbon multiple bonds, Carbon- hetero multiple bonds. 5. Elimination Reactions: E2, E1CB and E2C mechanisms and orientation in Pyrolytic eliminations, effect of substrate structure, Attacking base, leaving group and reaction bond, medium and reactivity addition to carbon carbon multiple bond reactions: mechanisms, Orientation and reactivity. 6. Electrocyclic, pericyclic and sigmotropic reactions: introduction, terminology and mechanism with suitable examples. 7. Concepts of aromaticity involving ring systems and anti aromaticity. Aromatic Substitution reactions, Electrophilic aromatic substitution. Mechanisms, Orientation and reactivity. 8. Molecular Rearrangements & their applications: Carbon to Carbon Migration: Wagner Meerwin rearrangement, Claisen rearrangement and benzyl benzylic acid rearrangement. Carbon to Nitrogen Migration: Hoffmann rearrangement, Curtius rearrangement and Lossen rearrangement, Beckman rearrangement. Carbon to Oxygen Migration: Bayer Villiger rearrangement, Rearrangement of hydro peroxides and Wittig rearrangement. Recommended Books Francis A. Carey & Richard J. Sunberg, Advanced Org. Chemistry , 3rd Edition , Part B; Reactions and synthesis , Plenum Press, new York , London , Latest Edition. Eliel I. Ernest and Samuel h, Stereochemistry of Org. Compounds, John Wiley and sons, New York, 2003 Edition. Roland E. Lehr & Alan P Marchard, Orbital Symmetry: A Problem solving approach, Latest Edition, Academic Press, New York J. March , Advanced Org. Chemistry, Reactions Mechanisms and Structure , 4th Edition, Latest Edition, John Wiley & Sons , New York. I. L. Finar , Organic Chemistry , ELBS Herbert O. Modern Synthesis Reactions IInd Edition W.A. Beenamis Inc. Menco Park California W. Carruthers, Some Modern Methods of Org. Synthesis, 3rd Edition, Cambridge University Press, Cambridge. JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY ANANTAPUR M.Pharm Pharmaceutical Chemistry I year I semester ADVANCED MEDICINAL CHEMISTRY I Theoretical Aspects of Drug Action Types of drug action, Physiochemical parameters and pharmacological activity. Non empirical Electronic parameters, stearic parameters and Stereo Chemical aspects of Drugs. Drug Receptors, Receptor types and isolation, Drug Receptor Interaction, theories of drug action, mechanism of drug action. Drugs acting on histamine receptors: Bio-synthesis and inactivation of histamine receptors and their classification into H1, H2 and H3 sub types. H1 receptor agonists: Synthesis of histamine H1 receptor antagonists: Synthesis of chloropheniramine H2 receptor agonists: Structure of impromidine H2 receptor antagonists: Synthesis of ranitidine, cimetidine and famotidine Amino acid receptors: Introduction, classification into inhibitory and excitatory amino acid receptors. Biosynthesis and inactivation of GABA, Glutamic acid and Aspartic acid GABA Agonists: Synthesis of Baclofen. Structures of muscimol, thiomuscimol and dihydromuscimol GABA Antagonists: Synthesis of 5-Guanidine pentanoic acid and 5-Amino pentanoic acid. Drugs acting on ion channels: Introduction to structure of cell membranes and ion channels. Drugs acting on Ca++ channels: Synthesis and mode of action of Nefidepine and diltiazem Drugs acting on Na+: Synthesis of tetracaine, amethocaine, etidocaine and lidocaine. Drugs acting on K+ channels: Synthesis of 4-Amino pyridine. Neurotransmitters and their receptors: Adrenergic receptors: Biosynthesis and inactivation of adrenergic neurotransmitters. Adrenergic receptors their classification into  and  sub types. Drugs affecting adrenergic neuro transmission: Drugs acting on biosynthesis of adrenergic neurotransmitters(Metyrosin), Drugs effecting catecholamine storage and release(Reserpine) - Adrenergic receptor agonists: Synthesis of Norepinephrine, Epinephrine and methyl dopa. - Adrenergic receptor antagonists: Structural formulae of APC and Benextramine. Synthesis of phenoxy benzamine, Terazosin and prazosin  - Adrenergic receptor agonists: Synthesis of Dobutamine, Salbutamol  - Adrenergic receptor antagonists: synthesis of popranalol and atenolol Cholinergic receptors: Biosynthesis and inactivation of Acetyl choline.Cholinergic receptors and their classification into muscarinic and nicotinic receptors. Chlinergic agonists: Synthesis of acetyl choline, carbacol and bethanecol Cholinesterase inhibitors: Synthesis of Physostigmine and structure neostigmine Cholinergic antagonists: Muscarinic antagonists Atropine (Only structure), Ganglionic antagonist- Nicotine, neuromuscular antagonists-Tubercurarine (Only structure) and synthesis of succinylcholine Dopamine receptors: Biosynthesis and inactivation of dopamine receptors Dopamine agonists: Synthesis of L-Dopa, fenoldapam Dopamine antagonists: Synthesis of chlorpromaizine Serotonin agonists: Synthesis of serotonin Serotonin antagonists: Synthesis of metaclopramide. Targets for the development of following chemotherapeutic agents: Anti-tubercular, Anti-HIV, anticancer, antifungal, Immuno-modulators, anti-amoebic drugs. Targets for the development of following pharmacodynamic agents Antiulcer, Analgesic, Anti Inflammatory, Anti atherosclerotic, Anti- angiogenesis, Anti hypertensives. Biotransformation of drugs- Prodrug approach, Soft Drug approach, enzymes responsible for biotransformation, microsomal and non microsomal mechanisms. Factors influencing enzyme induction and inhibition. Recommended Books Richard B. Silvermann, Org. Chemistry of Drug Design and drug Action. Bergers Medicinal Chemistry and Drug Design. 6th Edition. Korolkovas, Essentials of Medicinal Chemistry Purcell, Strategies of Drug Design Alfred Berger, Biochemical Basis of Drug Design Corwin , Hansen, Comprehensive Medicinal Chemistry William O Foye, Medicinal Chemistry Testa B and Jenner P. ,Drug Metabolism Chemical & Biochemical Aspects, Marcel Dekker Gyorgy Keri & Istdan Toth, Molecular Pathomechanism and New Trends in Drug Research, Taylor & Francis Pub. Ariens, Drug design medicinal chemistry a series of monograph-volume 11- III, academic press, an imprint of Elsevier pub. JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY ANANTAPUR M.Pharm Pharmaceutical Chemistry I year I semester MODERN PHARMACEUTICAL ANALYSIS - PRACTICAL Simultaneous estimation of Paracetamol and Ibuprofen, Rifampicin and INH, Aspirin and Caffeine. UV-Visible spectrum scanning of certain organic compounds- absorption and co-relation of structures, comparisons. Ex: a. Chloramphenicol b. Sulphadiazine c. Analgin Effect of pH and solvent on UV spectrum of certain drugs. Two dimensional paper chromatography and TLC. Gradient elution and other techniques in column chromatography. Separation by electrophoresis.(PAGE and agarose Gel electrophoresis) Experiments based on HPLC and GC. IR, NMR and Mass spectroscopy of compound each. DSC/XRD curves of a sample and mixture to understand polymorphism. Determination of insulin / any other hormones by ELISA method. JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY ANANTAPUR M.Pharm Pharmaceutical Chemistry I year I semester ADVANCED PHARMACEUTICAL CHEMISTRY - I PRACTICAL Preparation of Benzoneloid from benzophenone (Beckminn rearrangement) (Benzophenone----Benzophenoneoxime----Benzanilide) Preparation of 2-phenol indole from acetophenone (Fishcher indolization). (Acetophenone---- Acetophenone phenyl hydrazine----2-phenyl indole) Preparation of anti-pyrine from ethyl acetoacetate.(ethylacetoacetate----3-methyl-1-phenyl pyrazole-5-one----2,3-dimethyl-1-phenyl pyrazole-5-one) preparation of dobromocynamic acid from benzaldehyde (Perkins reaction) (Benzaldehyde----cinnamic acid----dibromocynamic acid) Preparation of 2,5-dihydroxy acetophenone from hydroquinone (Fries rearrangement) (Hydroquinone---- Hydroquinone diacetate----2,5-dihydroxyacetoquinone). Preparation of diethyl fumarate from mallic acid(racemisation) Mallic acid----fumaric acid----diethyl fumarate) Preparation of 2,2-dihydroxy-1,1-biphenyl naphthal from 2-naphthal (oxidation and free radical coupling) Preparation of Benzylic acid from Benzyl (Benzylic acid rearrangement). Qualitative analysis: A minimum of 8 organic binary mixtures and 4 tertiary mixtures should be analyzed systematically by either separation technique or with the preparation of at least one derivative in each compound. JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY ANANTAPUR M.Pharm Pharmaceutical Chemistry I year II semester DRUG DESIGN Drug Discovery: introduction to drug discovery, without lead- serendipity-penicillin and Librium as examples. Lead discovery- random and non-random screening of natural products-medical folklore; synthetic banks. Existing drugs from natural ligand and modulator. Combinatorial synthesis, computer aided designing (introductory treatment only). Principles of Drug Design: Structure pruning techniques in drug design, development of bioprecurssors, prodrugs and softdrugs. STAR Studies: Introduction to structure Activity relationship (SAR) studies (i) Binding role of hydroxyl group, amino group, aromatic ring, double bond, ketones and amides. (ii) Variation of substituents Alkyl substituents, aromatic substituents, extention of structure, chain extension / contraction, ring expansion / contraction, ring variation, ring fussion. Isosteres. (iii) Simplification of structure, rigidification, conformational blockers, X-ray crystallographic studies. Rational Drug Design: QSAR; parameters involved in QSAR, lipophilicity (polarisability, electronic and stearic parameters). Quantitative models Hansch analysis, free Wilson analysis and their relationships, linear relationships and applications of Hansch and free Wilson analysis. Molecular Modeling Drug Design: Molecular mechanism, quantum mechanism of known receptor sites: Definition, characterization of sites, design of ligands, visually assisted three dimensional data bases and calculation of drug affinity. Molecular mechanism, quantum mechanism of unknown receptor sites. Design of Local Anesthetics: Introduction, general considerations on the development of new drugs, classical and rational procedures for the development of local anesthetics Pharmacokinetic Oriented Drug Design: Drug Solubility: Solubility, varying polarity, varying Pka. Drug Stability: Stability, metabolic blocking, replacing metabolically susceptible groups, steric shields, electronic effects, stereochemistry, synergistic drugs, decreasing drug stability. Preclinical Testing and Clinical Trails: Toxicology, Pharmacology and pharmaceutical chemistry, drug metabolism studies, clinical trails, regulatory affairs. Recommended Books Burgers Medicinal Chemistry and Drugs Design 6th edition by Manfred E. Wolf. Introduction to Medicinal Chemistry by G. Patrick. Introduction to Drug Design by Silverman. Principles of Medicinal Chemistry Vol-I and II by Kadam etal. Principles of Medicinal Chemistry by William Foye. Medicinal Chemistry by Ashtoshkar. fda.org, wipo.int, patentlawlinks.com, hc-sc.gc.ca, ich.org, cder.org JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY ANANTAPUR M.Pharm Pharmaceutical Chemistry I year II semester ADVANCED PHARMACEUTICAL ORGANIC CHEMISTRY II Synthetic Reagents & Applications: Lead Tetra Acetate (LTA), N- Bromosuccinimide (NBS), Osmium Tetroxide, Lithium Aluminum Hydroxide and Sodium Bromohydride. Unit Process in Organic Synthesis: Catalytic hydrogenation, Nitration, Sulphonation, Halogenation, Amination, Acetylation, Esterification and Hydrolysis. Scale Up Techniques for process optimization, Maximization of productivity, in process control techniques with examples. Chemical Technology of selected bulk drugs Ibuprofen, Paracetamol, Ciprofloxacin and Isosorbide Nitrate. Synthetic Strategies-I : Introduction, target selection , disconnection approach; functional group inter conversions; synthons; reagents; retro synthesis; region selectivity; linear and convergent synthesis. Synthetic Strategies-II : One group disconnections; two group disconnections; Strategic bonds; criteria for disconnection of strategic bonds in carbocyclic and heterocyclic rings; biomimetic approach; retro mass spectral fragmentation-case studies of (+) Disparlure, retronecine and longifoline. Combinatorial Chemistry Parallel Synthesis (Houghtons teabag procedure, automated parallal synthesis), real combinatorial chemistry and deconvolution methods. Modern Synthetic methods-I: Green synthesis: Introduction; green reagents; green catalysts; ionic solvents; phase transfer catalysis in green synthesis; application of phase transfer catalysts in green synthesis of heterocyclic compounds: Williamsons synthesis, Wittig reaction. Modern Synthetic methods-I: Microwave assisted synthesis: Introduction; Microwave reactions in water (Hoffman elimination, hydrolysis and oxidation); microwave reaction in organic solvents; Solid state reactions; advantages of microwave technique. Recommended Books W. Caruthers , Some Modern Methods of Org. Synthesis , III rd Edition , Cambridge University Press, Cambridge(1988) Groggin's, Unit process in Org. Synthesis, McGraw Hill Book Crop. S. Warren, Org. Synthesis. The Disconnection Approach, J. Wiley & Sons. NY Gorgy Keri and Istarian Toth , Molecular Patho-mechanisms and New Trends in Drug Research Taylor and Francis Group ,London 2003 New trends in Green Chemistry-VK Ahluwalia & M Kidwai R.K. Mackie , A Guidebook to Organic Thesis Prentice Hall T.W. Greene and PGM Warts ,Protecting Groups John Willey Michael B. Smith , Organic Synthesis JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY ANANTAPUR M.Pharm Pharmaceutical Chemistry I year II semester ADVANCED MEDICINAL CHEMISTRY II Enzyme Inhibitors: A detailed study of the following types of enzyme inhibitors ,related drugs and their pharmaceutical significance : P.G. Synthetase (Cycloxygenase & Lipoxygenase Inhibitors) Phosphodiesterase (PDE ) Inhibitors Carbonic Anhydrase Inhibitors. Angiotensin Converting Enzyme (ACE) Inhibitors Acetyl Cholinesterase (Ach E) Inhibitors. Antipsychotic Agents: Roll of Dopamine, Serotonin, Glutamate and their receptors. SAR and Pharmacokinetics of Ticyclic Neuroleptics, Butyrophenones and Benzamides. A brief account of non benzodiazepine agonist 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; synthesis of chlorpromazine, prochlorperazine, fluphenazine, haloperidol. Anxiolytics, Sedatives and Hypnotics: Benzodiazepines and related compounds; Barbiturates, other classes, mechanism of action, SAR, uses and toxicity, synthesis of chlordiazepoxide, diazepam alprazolam, Phenobarbital, meprobamate. Antidepressants: MAO Inhibitors; tricyclic antidepressants, SAR, mechanism of acton, uses, toxicity, other classes like: Selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, newer (non-tricyclic) non selective 5-HT and NE reuptake inhibitors; selective serotoninergic reuptake inhibitors and 5-HT2A antagonists; 5-HT1A agonists and partial agonists and 2-antagonists. Synthesis of tranylcypromine, amitriptyline, fluxetine, buspirone. Antiepileptics and CNS stimulants a. Antiepileptics: Screening methods, classification of epilepsies, symptoms, drugs used, classification, structural features common to drugs, SAR, mechanism of action, toxicity and uses, synthesis of diphenylhydentoin, carbamazepine, sodium valporate. b. CNS stimulants: An account of the drugs with CNS stimulant activity, structures and uses. 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, miscellaneous diuretics, emerging developments in the use of diuretics to treat hypertension and congestive heart failure. A study of Antihyperlipidemic agents Phosphodiesterase inhibitors Quinolone antibacterial agents. Recommended Books Wilson and Gisvolds text book of pharmaceutical organic medicinal chemistry. Gorgy Keri & Istdan Toth Molecular Pathomechanism and New Trends in Drug Research, Taylor & Francis Pub Thomas Nogrady, Medicinal Chemistry. A biochemical Approach, Oxford Univ. Press. Organic chemistry of synthetic drugs- Lednicer. Bergers medicinal chemistry and drug design 6th edition. Richard. B. Silverman, Organic chemistry of drug design and drug action. Smith and Williams, Introduction to principles of drug design, Harwood Academy press. JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY ANANTAPUR M.Pharm Pharmaceutical Chemistry I year II semester ADVANCED CHEMISTRY OF NATURAL PRODUCTS (A) General Methods of Extraction, Qualitative chemical test for the detection of various Natural product compounds. (B) Study of herbal extracts processing, equipment and analytical profile of extracts of Drugs. Isolation/Separation techniques The technique and application of thin layer chromatography and preparative TLC, column chromatography medium and high-pressure liquid column chromatography, flash chromatography, HPTLC, HPLC and GC normal and reverse phase techniques. Alkaloids - Introduction, general methods of structure elucidation, chemistry and structure elucidation of morphine, reserpine and quinine. Isolation procedure of piperine and quinine. Steroids Introduction, nomenclature and stereochemistry, chemistry of cardiac glycosides, progesterone, oestradiol, cortisone, testosterone, bile acids, chemistry and structure elucidation of cholesterol, testosterone, progesterone. Synthesis of stilbesterol & hexesterol Isolation procedure of diosgenin and sennosides. Polypeptides and Proteins Introduction and general methods of separation, general methods of degradation and end group analysis, general methods of synthesis of peptides, Sequence analysis, secondary and tertiary structure of proteins, chemistry of insulin. Natural Products as Leads for New Drugs Introduction/History, approaches to discovery and development of natural products as potential new drugs, selection and optimization of lead compounds for further developments from CNS, anti cancer, antibiotic and cardiovascular drugs. Anticancer agents of natural origin Alkaloids of Vinca rosea: Vincristine and vinblastine- structures and SAR, semi synthetic derivatives, mechanism of action, uses and toxicity. Source and structures of Podophyllotoxin, taxol and camptothecin, semi synthetic derivatives, mechanism of action, uses and toxicity. 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, mitomcins, streptozocin. Anticancer agents from marine organisms-Bryostatin, dolastatin etc. Steroidal hormonal drugs: Steroidal antifertility agents: Estrogens, pregnane progestins, development of 19- norandrostanes, structures, mechanism of actions, regimen, toxicity. Anabolic steroids: Rationale for development, structures, uses, limitations Steroids in the treatment of cancers: Estrogens, Antiestrogens, Aromatase inhibitors, progestins, progestin antagonists, androgens and anabolic steroids, antiandrogens, 5- reductase inhibitors, gonadotropin inhibitors, glucocorticoids. Recommended Books Organic Chemistry Vol. 2nd by I. L. Finar Org. Chemistry by Morrison & Boyd Alkaloids  Chemical & Biological Prospective by S. W. Pelletier Steroids by Fischer and Fischer Pharmacognosy by Trease & Evans Chemistry of Natural Products Ata Ur Rehman Natural Products A Lab Guide by Raphael Ikon Wilson and Gisvolds text book of pharmaceutical organic medicinal chemistry. 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Atropine, caffeine, Ephedrine, Saponification of Trimyristin. Mini Projects: The mini projects can be taken up as industrial visit/training and report submission. Or A suitable project shall be carried out in the college. 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