Medicinal Chemistry in NIPER
Medicinal Chemistry in NIPER
Medicinal Chemistry in NIPER
I Semester
MC-510 Basics of Drug Action (2 credits)
1. Structure: 2D vs 3D. Structure vs. Electronic structure. Electronic structure of ketenes and its
importance in reactivity. Diels-Alder reaction, Symmetry using group theory. Graph theory and
2D structure.
2. Energy: Energy concept and its importance in drug action. First, Second and Third laws of
thermodynamics and the principles derived from these laws which are of significance to drug
action.
3. Thermodynamics: Free energy and Relationship between thermodynamics and statistics.
Importance of chemical potential in drug action. Thermodynamic cycle. Statistical
thermodynamics in predicting the structure of biomolecules and their interaction with drug
molecules. Macromolecular vs. micromolecular correlation using thermodynamics and
statistical thermodynamics.
4. Interactions: Inter- and intramolecular interactions. Weak interactions in drug molecules. Chirality
and drug action. Covalent, ion-ion, ion-dipole, Hydrogen bonding, C-H hydrogen bonding,
dihydrogen bonding, Van derWaals interactions and the associated energies.
5. Receptorology: Drug-receptor interactions, Receptor theories and drug action: Occupancy
Theory, Rate Theory, Induced Fit Theory, Macromolecular perturbation theory, Activation-
Aggregation theory. Topological and stereochemical consideration.
6. Enzyme Kinetics: enzyme kinetics in drug action. Do all molecules of an enzyme have same
kinetics? Mechanisms of enzyme catalysis, Electrostatic catalysis and desolvation. Covalent
catalysis, Acid-base catalysis, Strain / distortion in enzyme catalysis. Coenzyme catalysis.
7. Enzyme Inhibition: Drug action through enzyme inhibition. Examples based on PDE4, GSK3,
etc. Theories of enzyme inhibition and inactivation. Enzyme activation of drugs prodrugs.
8. Nucleic acids: NA as targets for drug action. NA-interactive agents. Classes of drugs that
interact with nucleic acids. Intercalation, NA-alkylation, NA-strand breaking and their importance
in drug action.
9. Drug likeness: Drug like molecules and theories associated with the recognition of drug like
properties. Physical organic chemistry of Drug metabolism, drug deactivation and elimination.
10. Drug action after Metabolism: Phase I and Phase II transformations. Concept of hard and soft
drugs. Chemistry of ADME and Toxicity properties of drugs.
Recommended Books:
1. The Organic Chemistry of Drug Design and Drug Action by R.B. Silverman
2. C.J. Coulson, Molecular Mechanism of Drug Action by C.J. Coulson
3. A primer of Drug Action by R.M. Julien
4. Drug-Receptor Thermodynamics by R.B. Raffa
5. Principles of Drug Action by W.B. Pratt, P. Taylor
6. Medicinal Chemistry How Drugs Act and Why by A. Gringauz
7. Principles of Molecular recognition by A.D. Buckingham
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4. Mass spectrometry (MS): Molecular ion and metastable peak, fragmentation patterns, nitrogen
and ring rules, McLafferty rearrangement, electron and chemical ionization modes, applications.
Recommended Books:
1. Spectroscopy by Donald L Pavia, Gary M Lampman, George S Kriz, James A Vyvyan
2. Organic spectroscopy by William Kemp
3. Spectroscopic Methods in Organic Chemistry by Dudley H. Williams & Ian Fleming
4. Spectrometric Identification of Organic Compounds by Robert M. Silverstein, Francis X. Webster
& David J. Kiemie
5. Applications of Absorption Spectroscopy of Organic Compounds by Dyer
6. Fundamentals of Molecular Spectroscopy by Colin N. Banwell & Elaine M. McCash
7. Spectroscopy by Pavia, Donald L. Lampman, Gary M. Kriz, George S.
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Recommended Books:
1. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure by Michael B.
Smith, and Jerry March
2. Designing Organic Syntheses by Stuart Warren
3. Organic Synthesis: the Disconnection Approach by Stuart Warren
4. Advanced Organic Chemistry: Reactions and Synthesis, Part A: Structure & Mechanism by
Francis A. Carey; Richard J. Sundberg
5. Advanced Organic Chemistry: Reactions and Synthesis, Part B: Reaction & Mechanism by
Francis A. Carey; Richard J. Sundberg
6. Modern Synthetic Reactions by Herbert O. House
7. Modern Methods of Organic Synthesis by Carruthers, William Coldham, Iain
8. Mechanism and Structure in Organic Chemistry by Gould
9. Advanced Inorganic Chemistry by Cotton , Wilkinson, Murillo and Bochmann
10. Fundamentals of Medicinal Chemistry by Thomas ISBN047084307
In each case the treatment of the topic starts from the entry level discussion from the above text/
reference books followed by relevant research articles from the original research work as well as
review articles. Such suggested readings are provided along with the progress of the lectures.
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II Semester
MC-610 Drug Design (2 credits)
1. Electronic Structure methods: Quantum chemical methods semi-empirical and ab initio
methods. Conformational analysis, energy minimization, comparison between global minimum
conformation and bioactive conformation. Predicting the mechanism of organic reactions using
electronic structure methods. Complete and constrained conformational search methods, their
advantages and disadvantages. Theoretical aqueous solvation calculations for design of ligands.
Conformational interconversion, transition-state determination and their role in designing rigid
analogs.
2. Quantum chemical methods of analyzing drugs: Metformin, its comparison to carbones, rapid
racemization in glitazones, metabolism and toxicity of troglitazone, conversion of proguanil to
cycloguanil.
3. Molecular modeling: Energy minimization, geometry optimization, conformational analysis,
global conformational minima determination; approaches and problems. Bioactive vs. global
minimum conformations. Automated methods of conformational search. Advantages and
limitations of available software. Molecular graphics. Computer methodologies behind molecular
modeling including artificial intelligence methods.
4. Structure Activity Relationships in drug design: Qualitative versus quantitative approaches-
advantages and disadvantages. Random screening, Non-random screening, drug metabolism
studies, clinical observations, rational approaches to lead discovery. Homologation, chain
branching, ring-chain transformations, bioisosterism. Insights into molecular recognition
phenomenon. Structure based drug design, ligand based drug design.
5. QSAR: Electronic effects: Hammett equation, lipophilicity effects. Hansch equation, steric
effects. Taft equation. Experimental and theoretical approaches for the determination of physico-
chemical parameters, parameter inter-dependence; case studies. Regression analysis,
extrapolation versus interpolation, linearity versus nonlinearity. Descriptor calculation. The
importance of biological data in the correct form; 2D QSAR; 3D-QSAR examples of CoMFA
and CoMSIA.
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6. Molecular docking: Rigid docking, flexible docking, manual docking. Advantages and
disadvantages of Flex-X, Flex-S, Autodock and Dock softwares, with successful examples.
7. Molecular dynamics: Dynamics of drugs, biomolecules, drug-receptor complexes, Monte Carlo
simulations and Molecular dynamics in performing conformational search and docking.
Estimation of free energy from dynamical methods.
8. Pharmacophore concept: Pharmacophore mapping, methods of conformational search used
in pharmacophore mapping. Comparison between the popular pharmacophore methods like
Catalyst/HipHop, DiscoTech, GASP with practical examples.
9. De Novo drug design techniques: Receptor/enzyme cavity size prediction. Predicting the
functional components of cavities, designing drugs fitting into cavity.
10. Informatics methods in drug design: Informatics methods in drug design: Brief introduction to
bioinformatics, chemoinformatics. Their relation to drug design as per the topics discussed in
items 1-9 above.
Recommended books:
1. Molecular Modelling, by A. R. Leach
2. Organic Chemistry of Drug Design and Drug Action, by R.B. Silverman
3. Practical Applications of computer aided drug design, by P.S. Charifson
4. Molecular modeling in Drug Design, by C. Cohen
5. Chemical Applications of Molecular modeling, by J. Goodman
6. Pharmacophore perception, by O.F. Guner
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Recommended books:
1. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure by Michael B.
Smith, and Jerry March
2. Advanced Organic Chemistry: Reactions and Synthesis, Part A: Structure & Mechanism by
Francis A. Carey; Richard J. Sundberg
3. Advanced Organic Chemistry: Reactions and Synthesis, Part B: Reaction & Mechanism by
Francis A. Carey; Richard J. Sundberg
4. Modern Synthetic Reactions by Herbert O. House
5. Modern Methods for Organic Synthesis, W. Carruthers and Iain Coldham
6. Asymmetric Synthesis, Vol 3, Editor: J. D. Morrison Advanced Organic Chemistry by March
7. Mechanism and Structure in Organic Chemistry by Gould
8. Advanced Inorganic Chemistry by Cotton , Wilkinson, Murillo and Bochmann
9. Fundamentals of Medicinal Chemistry by Thomas
10. Web resources
In each case the treatment of the topic starts from the entry level discussion from the above text/
reference books followed by relevant research articles from the original research work as well as
review articles published in peer reviewed journals of international repute. Such suggested readings
are provided along with the progress of the lectures.
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Recommended books:
1. Physical Biochemistry: Applications to Biochemistry and Molecular Biology by David Freifelder
2. Methods in Modern biophysics, by B. Nolting
3. Introduction to Biophysical methods in Protein and Neucleic Acid research, by J.A. Glasel
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Recommended books:
1. StereoChemistry of Organic Compounds by Ernest L. Eliel, Samuek H. Wilen, Lewis N. Mander
2. StereoChemistry of Carbon Compounds by Ernest L. Eliel
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