Course

Unit 1

Drug Discovery and Drug Target 12 Hrs

a.Drug discovery: Stages of drug discovery, Lead discovery and identification, validation. (4hrs) b.Biological drug targets:

Preliminary Reading: Receptors, types, binding, and activation,

Theories of drug-receptor interactions, drug-receptor interactions agonists vs antagonists. Artificial enzymes. (1hr)

c. Stereochemistry and Drug action:

Realization that stereo selectivity is a prerequisite for evolution. (2hrs). Role of chirality in selective and specific therapeutic agents (Case studies),

Enantioselectivity in drug adsorption, metabolism, distribution, and elimination. (5hrs)

Unit 2

Prodrug and Analog design 12 Hrs

1. Prodrug design:

Basic concept of prodrugs, carrier-linked prodrugs/ Bioprecursors, Strategies to design Prodrugs incorporating different functional groups and Prodrugs to improve patient acceptability, Drug solubility, Drug absorption and distribution, site-specific drug delivery, and sustained drug action. (2hrs)

Rationale of prodrug design and practical consideration of prodrug design. (2hrs)

1. Combating drug resistance: Causes for drug resistance, Chemo-strategies to combat drug resistance in antibiotics and anticancer therapy. (2hrs)

Design of antibiotics and anticancer drugs in combating drug resistance. Genetic principles of drug resistance. (2hrs)

c) Analog Design:

Preliminary Reading: Introduction, Classical and non-classical bioisosteres.

Bioisosteric replacement strategies, rigid analogs, alteration of chain branching, changes in ring size, ring position isomers, design of stereoisomers and geometric isomers, fragments of a lead molecule, and variation in inter-atomic distance. (4hrs)

Unit 3

Rational Design of Enzyme Inhibitors 10 Hrs

Preliminary Reading: Enzyme kinetics and principles of Enzyme inhibitors

Enzyme inhibitors in medicine and basic research (5hrs)

Rational design of non-covalently and covalently binding enzyme inhibitors.(5hrs)

Unit 4

Peptidomimetics 11 Hrs

Preliminary Reading: Chemistry of prostaglandins, leukotrienes, and thromboxanes

Therapeutic values of Peptidomimetics, Design of peptidomimetics by manipulation of the amino acids. (6hrs)

Modification of the peptide backbone, Incorporating conformational constraints locally or globally. (5hrs)

The course is designed to impart a solid understanding of the principles and concepts underlying the stages of drug discovery and development, in the field of medicinal chemistry at the molecular level including different techniques for rational drug design. The course will provide a better understanding of the role of stereochemistry in drug-receptor interactions, including recognition of chiral centers, enantiomeric purity assessment, and prediction of stereochemical effects on drug potency and selectivity.

The course also provides knowledge on prodrug and analog design strategies, including rational modifications to enhance pharmacokinetic properties, optimize drug-receptor interactions, and mitigate off-target effects while improving therapeutic efficacy. The course emphasizes various chemotherapeutic strategies to combat drug resistance, including the identification of resistance mechanisms and, development of resistance mitigation approaches.

The course provides in-depth knowledge in designing and optimizing peptidomimetics as drug candidates, including rational design based on peptide structure-function relationships, structural biology techniques, and computational modeling to improve stability, bioavailability, and target specificity. The course outlines various principles including understanding enzyme kinetics and mechanisms, rational design based on structural biology and computational modeling, and optimization of inhibitor potency and selectivity.

Upon successful completion of the course, the student shall be able to;

KNOWLEDGE

K1: Discuss the different stages of drug discovery and the role of medicinal chemistry in drug research

K2:Apply stereochemical principles to design drugs with desired stereoselective properties, considering factors such as chirality, conformational flexibility, and stereochemical constraints.

K3:Acquire proficiency in designing and optimizing prodrug strategies to enhance drug delivery, improve bioavailability, and minimize adverse effects.

K4: Employ the principles of analog design to structure rational analogs with improved potency, selectivity, and pharmacokinetic profiles to address therapeutic challenges such as drug resistance, metabolic stability, and off-target effects

K5: Analyze the principles underlying enzyme inhibition, kinetics of enzyme-inhibitor interactions, and applications in medicine and basic research

K6: Explore various strategies of peptidomimetics with enhanced stability, selectivity, and pharmacokinetic properties for introducing conformational constraints into peptidomimetics

SKILL

S1: Acquire the ability to critically search scientific literature, extract relevant information, and put in data analysis techniques to identify potential drug targets and therapeutic strategies.

S2: Predict the influence of stereochemistry on the biological activity and selectivity of chiral drugs, including interactions with target receptors and enzymes.

S3: Apply the principles of chemo strategies to design and mitigate antibiotic and anticancer drug resistance.

S4: Explore the principles of prodrug and analog design to modify drug structures and enhance their pharmacological properties, including potency, selectivity, and metabolic stability.

S5: Interpret structural data to guide the design and optimization of enzyme inhibitors.

S6: Employ various peptidomimetic design strategies, such as backbone modification, side chain substitution, cyclization, and conformational constraint, to enhance the stability, bioavailability, and pharmacological properties of peptides.

ATTITUDE

A1: Demonstrate a commitment to continuous learning and staying updated with advancements in the field of medicinal chemistry

A2: Motivate fellow beings to be good team players

A3: Follow a professional and ethical approach

A4: Exhibit good communication skills to emerge as compassionate pharmacy professionals.

A5: Demonstrate leadership quality in planning and executing experiments.

A6: Cooperate with other students within the team in laboratory practices.

1. Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry, 11^thed. Lippincott Williams & Wilkins: New Delhi;2009

2, Williams D.A. Foye’s Principles of Medicinal Chemistry,7^th ed. LPPWW Publishers: Philadelphia;2009

3. Patrick L. An Introduction to Medicinal Chemistry, 4^th ed. Oxford University Press: New York; 2009
4. Ilango K, Valentina Text Book of Medicinal Chemistry, Vol. I & II.1st ed. Keerthi Publishers: Chennai; 2012
5. Welly E., M.E. Walffred. Burger’s Medicinal Chemistry, Vol.1-6, Wiley Interscience Publication: New York;2009

JOURNALS

European Journal of Medicinal Chemistry, Publisher: Elsevier https://www.sciencedirect.com/journal/european-journal-of-medicinal-chemistry

Journal of Medicinal Chemistry, Publisher: American Chemical Society https://pubs.acs.org/journal/jmcmarChemMedChem

ACS Medicinal Chemistry letters, Publisher: American Chemical Society https://pubs.acs.org/journal/amclct

ASSIGNMENTS

1. Explain the role of medicinal chemistry in lead optimization and provide examples of chemical modifications used to improve lead compounds.

2 Examine the role of enzymes, pH conditions, and other physiological factors in prodrug activation.

3. Provide examples of successful drugs developed through analog design, highlighting the rationale behind specific modifications.

4 Analyze the outcomes of using racemic mixtures vs single enantiomers in drug formulations.