Advanced Medicinal Chemistry

The course is classified as a second-cycle course and can be read as a freestanding course.

The course can be part of the following programmes: 1) Master's Programme in Organic and Medicinal Chemistry (N2KEL) and 2) Master's Programme in Chemistry (N2KEM)

90 credits in chemistry, including KEM815, Advanced Organic Chemistry (15 credits) and KEM826 Organic Chemistry and Medicinal Chemistry (15 credits) or equal qualifications.

Applicants must prove their knowledge of English: English 6/English level 2 from Swedish Upper Secondary School or the equivalent level of an internationally recognized test, for example TOEFL, IELTS.

The course is intended to give advanced knowledge in design, synthesis and biological evaluation of small organic substances as potential lead compounds.

A. Theory

Design of substances

• Lead identification and lead optimisation: target selection, hit finding, SAR and structure-activity reasoning
• Physicochemical properties and drug-likeness: solubility, lipophilicity, permeability, stability, ADMET and developability
• Design of small-molecule leads, including heterocyclic scaffolds, halogen substitution and scaffold hopping
• Design principles for peptides, biologics and new modalities, including conjugates, antibody-drug conjugates and targeted delivery concepts
• Structure-based design: protein-ligand interactions, binding-site analysis, docking, pharmacophore models and selectivity
• Computational chemistry with emphasis on conformational analysis of proteins, peptides, and other modalities.

Synthesis of substances

• Retrosynthetic analysis and selection of practical synthetic routes for drug-like molecules
• Synthesis and functionalisation of medicinally relevant heterocycles and scaffold-based compound series
• Strategies for lead optimisation through late-stage functionalisation, halogenation and analogue synthesis
• Peptide synthesis, including solid-phase peptide synthesis, cyclisation and chemical modification to improve stability and pharmacokinetics
• Bioconjugation and ligation chemistry, including linker design, peptide/protein conjugation
• Analytical characterisation of synthetic compounds and peptides

Biological evaluation of substances

• Principles of assay selection in drug discovery
• Cell-free assays, whole-cell assays and cellular models for evaluating potency, selectivity, mechanism of action and toxicity
• Design and interpretation of cell-based assays

B. Computer exercises

Computer exercises include conformational analysis and modelling of selected modalities and proteins; docking; homology modelling; binding-site and interaction analysis.
Module reports use drug discovery case studies and are written in a short manuscript format with oral presentation and discussion.
Literature seminars train critical analysis of medicinal chemistry papers.

Knowledge and understanding

On completion of the course the student should be able to:

• describe strategies for design and optimisation of lead compounds and therapeutic modalities, including small molecules, peptides, biologics and conjugates
• explain how structure, conformation, physicochemical properties, assay data and developability guide medicinal chemistry decisions
• describe principles, applications and limitations of biochemical, cell-based and preclinical assays used to evaluate drug candidates.

Competence and skills

On completion of the course the student should be able to:

• use computational tools to analyse conformations of small molecules, proteins and new modalities, and to study ligand-target interactions
• apply structure-based and ligand-based reasoning to propose and prioritise compounds or modalities for further optimisation
• carry out basic retrosynthetic analysis and propose synthetic or modification strategies for medicinal chemistry targets
• use the scientific literature to frame a drug discovery question, identify relevant evidence and prepare manuscript-style module reports and oral presentations

Judgement and approach

On completion of the course the student should be able to:

• critically evaluate research publications, computational models, assay design and claims in medicinal chemistry
• judge what experimental or computational evidence is needed to support a lead optimisation decision
• clearly communicate conclusions, limitations and underlying arguments in written and oral form

The teaching is given in the form of lectures, group work, project assignments, computer exercises and literature seminars.

Group work, project assignments, computer exercises and seminars are compulsory.

Project assignments, which are presented in writing and orally, will underlie the course grade. A final examination, usually in writing, is arranged at the end of the course.

A student who has not passed the regular examination session is offered additional examination sessions.

If a student who has been failed twice for the same examination element wishes to change examiner before the next examination session, such a request is to be granted unless there are specific reasons to the contrary (Chapter 6 Section 22 HF).

If a student has received a certificate of disability study support from the University of Gothenburg with a recommendation of adapted examination and/or adapted forms of assessment, an examiner may decide, if this is consistent with the course’s intended learning outcomes and provided that no unreasonable resources would be needed, to grant the student adapted examination and/or adapted forms of assessment.

If a course has been discontinued or undergone major changes, the student must be offered at least two examination sessions in addition to ordinary examination sessions. These sessions are to be spread over a period of at least one year but no more than two years after the course has been discontinued/changed.

If a student has been notified that they fulfil the requirements for being a student at Riksidrottsuniversitetet (RIU student), to combine elite sports activities with studies, the examiner is entitled to decide on adaptation of examinations if this is done in accordance with the Local rules regarding RIU students at the University of Gothenburg.

The grading scale comprises: Pass with Distinction (VG), Pass (G) and Fail (U).

Sub-course 1: To obtain a Pass (G), students must achieve at least 50% of the maximum possible score on the written examination. To obtain a Pass with Distinction (VG), students must achieve at least 75% of the maximum possible score on the written examination.

Sub-course 2: To obtain a Pass (G), students must attend all compulsory course components and achieve a passing result (at least 50%) on the oral and written presentations. To obtain a Pass with Distinction (VG), students must pass all compulsory components of the sub-couse and achieve an average score of at least 75%.

Final grade: The final grade is determined by a weighted calculation of the results from sub-courses 1 and 2. For the final grade pass, G is required on sub-courses 1 and 2. For the final grade Pass with Distinction, G is required on sub-course 1 and 2 as well as an overall weighted score of at least 75% across the two sub-courses.

Students who participate in or have completed course should be given possibility to anonymously perform experiences of and views in the course in a course evaluation.

The results of and possible changes to the course will be shared with students who participated in the evaluation and students who are starting the course.

Language of instruction: English and Swedish

The course is given as principal rule in English but can be given completely or partly in Swedish if the circumstances admit this.