Design, Synthesis and Reactivity in Medicinal and Biopharmaceutical Chemistry

Course content

The course will focus on how drug molecules are designed and synthesized - from a chemical perspective. Thus, different ways of accessing pharmaceutically relevant compound classes will be investigated. Strategic considerations with respect the order of introduction of functional groups and linear/convergent approaches will be discussed and compared.

The course will be organized around specific reaction types and functional groups where the most efficient way of accessing these will be highlighted. Furthermore, consideration about the metabolic liability and possible biotransformation of different functional group will be covered to guide the design process of new drug molecules.

Specific themes that will be covered include:

  • Synthesis of drugs using state-of-the-art methodologies - Enantioselective synthesis, cross coupling ractions, C-H activation, etc.
  • Reactive functional groups in medicinal chemistry
  • Bioorthogonal chemistry
  • Biopharmaceuticals

 

Lectures on lead optimization and process development within the pharmaceutical industry will be given by researchers from the industry

Education

MSc Programme in Pharmacy or Pharmaceutical Sciences (Danish programmes cand.pharm and cand.scient.pharm) - elective

MSc Programme in Medicinal Chemistry - elective

MSc Programme in Pharmaceutical Sciences (English programme) - elective

Learning outcome

At the end of the course, students are expected to be able to:

Knowledge

  • identify the functional groups typically encountered in drug discovery and process development and reflect upon their reactivity and stability
  • explain basic elements of selected reaction mechanisms, such as cross-coupling reactions
  • summarize and critically evaluate strategies in modern organic synthesis as applied in lead optimization and process development cases in medicinal and biopharmaceutical chemistry
  • describe and discuss different types metabolic reactions, the reaction mechanism and propose typical reactive hot-spots as well as expected metabolites

 

Skills

  • master retro-synthetic strategies presented during the course
  • analyze and evaluate the use of protection groups in synthesis planning
  • assess and discuss biotransformation of functional groups in relation to selected drug discovery projects
  • critically review and present examples from the scientific literature

 

Competencies

  • design new drug candidates ligands where consideration about reactivity and metabolic liability are implemented
  • plan and discuss synthetic strategies for putative drug molecules relevant for early discovery

Before each session, a group of students will receive a scientific paper from journals, e.g. J. Med. Chem. or ACS Med. Chem. Lett. Their group task will be to read, analyze and elaborate, critically review and present their results to their fellow students. This will comprise a short description of the purpose/target, the methods applied, the chemistry described and a critical review of the efforts publish. When one group is presenting, one other group is appointed as ‘peer group’ and will have as a task to define and identify question for the presenting group.

To each theme, the students will have access to 6-8 multiple choice questions in Absalon. These questions are formulated in such a way that the students can solve them if they have read, worked with and understood the curriculum of the day. The Quizz with close as the lectures start and the Quizz Report will be evaluated and discussed in plenum with the students. The intention of these Assignment Quizzes is multifold:
1) To ensure the students work with the curriculum before attending the lectures
2) Reward and encourage the students professionally
3) Improve the student learning
4) Provide a live picture of the actual skill level and identify ‘easy’ and ‘difficult’ subjects.

The Quizz will be accompanied with more elaborate explanations for correct answers and help/guidelines for false answers. The Quizz will also be opened again as the students start preparing for the exams.

Furthermore, the course teachers will provide an overview lecture with focus and key learning elements in the subjects of the day. Each lecture will terminate with a summary of the major skills and competences acquired.

In addition, the course will also use classical problem solving and exercises in the classroom. They serve both as student activating initiatives and to break up lectures in pieces no longer than 20 minutes.

Reviews and original scientific papers will be available at the course homepage

Further recommended reading: Jonathan Clayden, Nick Geeves, Stuart Warren (2012) Organic Chemistry 2nd Edition; ISBN: 978-0199270293 Oxford University Press

 

Teaching is based on the assumption that the students have acquired knowledge, skills and competences corresponding to those obtained by completion of the first five semesters of the BSc Programme in Pharmacy.

Individual
Collective
Continuous feedback during the course of the semester
Peer feedback (Students give each other feedback)
ECTS
7,5 ECTS
Type of assessment
Other, 30 min
For the final assessment, students are divided into groups of three-four students.

Each group will receive a scientific paper and then have 48 hours to prepare a presentation in the form of powerpoint slides or a poster. The task will be to analyze, critically review and present the paper. Each student will have an individual assessment based on the presentation submitted by the group (max 10 min) followed by a discussion (max 10 min).
Aid
All aids allowed
Marking scale
passed/not passed
Censorship form
No external censorship
Criteria for exam assessment

To pass the course the student must be able to:

Knowledge

  • identify the functional groups typically encountered in drug discovery and process development and reflect upon their reactivity and stability
  • explain basic elements of selected reaction mechanisms, such as cross-coupling reactions
  • summarize and critically evaluate strategies in modern organic synthesis as applied in lead optimization and process development cases in medicinal and biopharmaceutical chemistry
  • describe and discuss different types metabolic reactions, the reaction mechanism and propose typical reactive hot-spots as well as expected metabolites

 

Skills

  • master retro-synthetic strategies presented during the course
  • analyze and evaluate the use of protection groups in synthesis planning
  • assess and discuss biotransformation of functional groups in relation to selected drug discovery projects
  • critically review and present examples from the scientific literature

 

Competencies

  • design new drug candidates ligands where consideration about reactivity and metabolic liability are implemented
  • plan and discuss synthetic strategies for putative drug molecules relevant for early discovery

Single subject courses (day)

  • Category
  • Hours
  • Lectures
  • 24
  • Class Exercises
  • 40
  • Preparation
  • 125
  • Exam Preparation
  • 16
  • Exam
  • 1
  • English
  • 206