Oct 22, 2020   5:55 p.m. Sergej
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Course syllabus N414M1_4B - Medicinal Chemistry (FCFT - SS 2019/2020)

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Slovak University of Technology in Bratislava
Course unit code:
Course unit title:
Medicinal Chemistry
Mode of delivery, planned learning activities and teaching methods:
2 hours weekly (on-site method)
1 hour weekly (on-site method)

Credits allocated:
Recommended semester/trimester:
Chemistry, Medical Chemistry and Chemical Materials - bachelor (compulsory), 6. semester
Level of study: 1.
Prerequisites for registration:
Assesment methods:
The exam consists of a written test and an oral test for 50 points. To successfully passing the exam, the student must achieve at least 28 points.
Students are grated as follows: A 46-50 points, B 41-45 points, C 37-40 points, D 32-36 points, E 28-31 points.
Learning outcomes of the course unit:
The aim of the course is to put a brief introduction to the problematic of the drug design. It involves most chemistry-related phases of this process, starting from the lead identification phase, based on certain therapeutic strategy or a molecular target, proceeding through the lead optimisation phase and ends in the phase of clinical testing. Later phases of formula development, production and marketing are not debated. The scaffold of the course is identical with all modern textbooks on medicinal chemistry, e.g. Graham L. Patrick: An Introduction to Medicinal Chemistry (4th edition, Oxford Press 2009) or Heinz Lülmann et all: Color Atlas of Pharmacology (2nd edition, Thieme Stuttgart, 2000)
Course contents:
Phases of drug development and their duration. The cost of drug development and economic aspects of development. Introduction to patent law. FDA and its international importance and competence. Types of FDA procedures. Phases of clinical trials and drug content. Types of dosage forms. Definitions pharmacokinetics and pharmacodynamics. Basic pharmacokinetic parameters and their interrelationships. Determination of the therapeutic benefits and principles of drug dosing. Clearance and its components.

Principle chemotherapy. Types of interactions between the drug and the receptor. Lipophilicity / Hydro, logP, measurement and calculation principle pinocytosis, liposomes. Lipinski selection rules, "drug likeness". Pharmacodynamics and its basic values, principles toxicity, modern tests and latent chronic toxicity: Ames test, hERG test, mikrojadierkový test.Signálny apparatus of the cell. Basic principles of signal transduction from membrane receptors to the effector protein. Membrane receptors and their function principle.

Basic principles of chemotherapy for receptor activity. Competitive and non-competitive inhibition, Lineweaver-Bourke charts. Allosteric effect and umbrella. Negative effects of receptor inhibitors: sensitization / desensitization, tolerance, dependency. Affinity, potency and effectiveness receptor inhibitor. Kinase kinase cascade classification of kinases. Izozýmy a problem izozýmovej selectivity. Effector proteins.

DNA and chromosome morphology. Recombinant DNA techniques. DNA and RNA vectors. PCR. Types of genetic manipulation. DNA interkalatujúce drugs and their use. DNA gyrase and topoisomerase. Classification and inhibitors of these proteins. Development of topoisomerase I inhibitors based on natural camptothecin. Nekamtotecínové topoisomerase inhibitors. DNA alkylating agents as a pseudoalkylačné kancerostatické substances. DNA terminators. Monoamine transporter proteins, molecular tunnel. Drugs acting on the formation and decomposition of the cytoskeleton.

Drug discovery and its phases. Lead identification and search strategy "lead" structures. Principles of screening. The definition of combinatorial chemistry, the concepts of virtual and real libraries, in-silico, in-vitro and in-vivo screening, HTS. Strategy design for general screening library. Methodology of libraries, software solutions for library enumeration and its virtual
profiling. Production libraries: the concept of parallel synthesis, examples of hardware for parallel synthesis. Principles for the development of synthetic procedures suitable for parallel synthesis. LP synthesis in MTP format, advanced liquid phase methods for the synthesis of amides and cross-coupling reactions.

Principles of screening. Synthesis on solid phase Merrifield peptide synthesis. Types of solid phases and linkers for SP responses. Assessment of the advantages and disadvantages of SP in parallel synthesis. Hardware for SP. A "mix and split". SP micromanipulation techniques, on-chip synthesis. Principle SAMDI / MALDI MS spectrometer as a basic analytical tool for on-chip reactions. On-chip PCR. Flow chemistry, parallel synthesis in a continuous flow microreactor. Screening of natural compounds. Comparison of screening natural

substances and general screening in terms of success, patent safety and economic performance. Development phase of the drug based on a natural substance for example camptothecin. Principles of screening according to the structure, CADD (computer aided drug design) and normal phase. Types of digital formats for writing molecular structure. Z-matrix, SMILES, Cartesian coordinates, type of database files. Sdf. Geometry optimization of the molecule, potential energy of the molecule, techniques and localization of total local minima and other extremes. Stationary points hyper, its first and second derivative (gradient, Hessian) and their significance. Methods for finding stationary points. Iterative methods, Monte-Carlo methods, molecular dynamics, simulated annealing.

Methods for calculating the energy of the molecule. Newtonian and relativistic methods (molecular vs quantum mechanics) and their comparison. Selection of molecular mechanical methods depending on the type of computer tasks. The principle Hartree-Fock, DFT and semiempirical methods for solving Schrödinger equation. Combined the method of calculating energy QM + MM, QM-MM. Molecular docking and its principles. Interaction energy, Connolly surface complementarity and dynamic sedimentation. Fragment-based screening and principle. Comparison with the general screening. Requirements fragments and linkers. Example FBS.

QSAR and its principles. The difference between 2D and 3D QSAR, the difference between 3D QSAR and molecular docking. Descriptor, the definition and types of descriptors. Basic QSAR equation: Free-Wilson, Hansch. coefficient hydrophobicity, electronic Hammett and Taft steric coefficient of determination, calculation and physical meaning. Topliss-scheme. Bioizostéry.

3D QSAR. Requirements for success 3D QSAR. Molecular field principle. Principle of the method Comfy based 3D descriptors derived from the description of the molecular field. Comparison Comfy and classical Hansch method, practical and economic arguments. VOLSURF and 3D descriptors.

Metabolism of drugs. Types of metabolic reactions. Methods for screening for metabolites. Methods for modification of metabolic drug resistance. Principle prodrug strategy classification prodrug drugs. Examples of prodrug drug first Class. VDEPT, ADEPT, GDEPT prodrug strategy for medicinal second Class.
Recommended or required reading:
HAMPL, F. -- PALEČEK, J. Farmakochemie. Praha : Vydavatelství VŠCHT, 2002. 413 p. ISBN 80-7080-495-5.
BERKEŠ, D. -- VINŠOVÁ, J. -- KUTSCHY, P. -- TOROK, M. Základy farmaceutickej chémie. Košice: UPJŠ, 2003. 150 p.
PATRICK, G L. An Introduction to Mediinal Chemistry. New York: Oxford University Press Inc., 2009. 752 p. ISBN 978-0-19-923447-9.

Heinz Lülmann et all: Color Atlas of Pharmacology (2nd edition, Thieme Stuttgart, 2000)

Language of instruction:
slovak or english
The course is recommended for students in the third year of study in the program Chemistry, medicinal chemistry and materials
Courses evaluation:
Assessed students in total: 542

2,4 %7,4 %
16,1 %
24,2 %
49,6 %
0,3 %
Name of lecturer(s): Ing. Matej Babjak, PhD. (examiner, instructor, lecturer) - slovak, english
doc. Ing. Dušan Berkeš, CSc. (person responsible for course) - slovak, english
Last modification:
29. 1. 2019
doc. Ing. Dušan Berkeš, CSc. and programme supervisor

Last modification made by Ing. Tomáš Molnár on 01/29/2019.

Type of output: