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HU Credits:
5
Degree/Cycle:
1st degree (Bachelor)
Responsible Department:
School of Pharmacy
Semester:
1st Semester
Teaching Languages:
Hebrew
Campus:
Ein Karem
Course/Module Coordinator:
Prof. Amiram Goldblum
Coordinator Office Hours:
Mon-Tue- Wed 13-19
Teaching Staff:
Prof Amiram Goldblum
Course/Module description:
Medicinal Chemistry: Principals and Application 64662
Teacher: Prof. Amiram Goldblum (Cell. 0544653292)
amiramg@ekmd.huji.ac.il
First Semester: Wednesdays 16-19, Fridays 12-14
Syllabus
A. Basics of Drug Action:
• General: Definitions, how are drugs discovered, Drug and Target. Molecular level of drug action, experimental support by X-ray crystallography, Nuclear Magnetic Resonance, Spectroscopy, Computations
• Biological targets: Proteins, Membranes, DNA/RNA, Water
• How do drugs bind to targets ? Molecular energy, Free energy, Enthalpy and Entropy, Hydrophobic effect
• Intermolecular interactions: strong and weak, electrostatics, hydrogen bonds, Van der Waals interactions
• Degrees of freedom and Entropy
• Drug properties: Electronic structure (Quantum mechanical), Frontier Orbitals, Acidity and basicity, conformations, volume, surface area, lipophilicity
B. Rational methods for drug design and discovery:
• Main current and future targets
• High Throughput Screening
• Structure-Activity relations: SAR and Quantitative SAR: Hammet and Hansch equations, Lipinski's rule of five
• Examples of Drug discovery by computaitons
• General approaches: Bioisosteres, Conformational restriction
• Multi-targeted drugs
C. Proteases and Enzyme activity – Drugs' viewpoint
• Enzymes: kinetics, catalysis, transition state, Michaelis-Menten approximation, Kinetic constants, inhibition equations and effects on Km and kcat.
• Protease families: serine, thiol (Cysteine), aspartic, metaloproteases: mechanisms, specificity and selectivity, associated diseases
• Protease inhibitors: reversible and irreversible, inhibitor design: minimal substrate, natural inhibitors, transition state analogs, intermediate's analogs
• Examples of protease inhibitors: use of crystallography and computations for AIDS drugs, ACE inhibitors for hypertension
• Why aren't there drugs that kill SARS-CoV-2 (COVID-19) ?
D. Drugs for receptors and channels
• GPCRS and membrane channels
• CNS drugs
• Cannabinoids and Psychotropic drugs
• Alzheimer's disease and Acetylcholinesterase
• Drugs for Genetic diseases of the young :Muscular Dystrophy
Course/Module aims:
1) Acquaintance with basic principals of drug action and their application ifor major drug-targets: enzymes and receptors
2) Understanding structure-activity relations
3) Understanding how a drug is "born" and how do medicinal chemists improve drugs
Learning outcomes - On successful completion of this module, students should be able to:
1) know the basics of drug action
2) have the ability to understand and to criticize issues of drug developments and reports that are raised in the public domain - news, popular reports etc.
Attendance requirements(%):
None
Teaching arrangement and method of instruction:
ZOOM + 3 frontal meetings
Course/Module Content:
Syllabus
A. Basics of Drug Action:
• General: Definitions, how are drugs discovered, Drug and Target. Molecular level of drug action, experimental support by X-ray crystallography, Nuclear Magnetic Resonance, Spectroscopy, Computations
• Biological targets: Proteins, Membranes, DNA/RNA, Water
• How do drugs bind to targets ? Molecular energy, Free energy, Enthalpy and Entropy, Hydrophobic effect
• Intermolecular interactions: strong and weak, electrostatics, hydrogen bonds, Van der Waals interactions
• Degrees of freedom and Entropy
• Drug properties: Electronic structure (Quantum mechanical), Frontier Orbitals, Acidity and basicity, conformations, volume, surface area, lipophilicity
B. Rational methods for drug design and discovery:
• Main current and future targets
• High Throughput Screening
• Structure-Activity relations: SAR and Quantitative SAR: Hammet and Hansch equations, Lipinski's rule of five
• Examples of Drug discovery by computaitons
• General approaches: Bioisosteres, Conformational restriction
• Multi-targeted drugs
C. Proteases and Enzyme activity – Drugs' viewpoint
• Enzymes: kinetics, catalysis, transition state, Michaelis-Menten approximation, Kinetic constants, inhibition equations and effects on Km and kcat.
• Protease families: serine, thiol (Cysteine), aspartic, metaloproteases: mechanisms, specificity and selectivity, associated diseases
• Protease inhibitors: reversible and irreversible, inhibitor design: minimal substrate, natural inhibitors, transition state analogs, intermediate's analogs
• Examples of protease inhibitors: use of crystallography and computations for AIDS drugs, ACE inhibitors for hypertension
• Why aren't there drugs that kill SARS-CoV-2 (COVID-19) ?
D. Drugs for receptors and channels
• GPCRS and membrane channels
• CNS drugs
• Cannabinoids and Psychotropic drugs
• Alzheimer's disease and Acetylcholinesterase
• Drugs for Genetic diseases of the young :Muscular Dystrophy
Required Reading:
popular literature on drugs will be posted to students
Additional Reading Material:
Course/Module evaluation:
End of year written/oral examination 100 %
Presentation 0 %
Participation in Tutorials 0 %
Project work 0 %
Assignments 0 %
Reports 0 %
Research project 0 %
Quizzes 0 %
Other 0 %
Additional information:
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