The aim of this module is to introduce students to the fundamental principles that underpin modern medicinal chemistry, including an introduction to targets for drug action, methods of administration, qualitative and quantitative SAR, natural products medicinal chemistry, kinase drug discovery and solid phase chemistry /combinatorial chemistry. The course will also introduce approaches to the design of high quality hits using fragment based drug design introducing the concepts of Ligand Efficiency, and Lipophilic Ligand Efficiency. The course has a strong industrial input and will involve guest lecturers from industry on a rotational basis.

(LO1) To explain the basic concepts of structure activity relationships (SAR) and quantitative structure activity relationships (QSAR), including the impact of structure in drug metabolism and recognition and interpretation of data on key quantitative parameters use to classify metabolic stability (clearance, half-life etc).

(LO2) To understand, apply and calculate the basic concepts of drug optimisation with respect to Lipinski’s rules, Ligand Efficiency (LE) and Lipophilic Ligand Efficiency (LLE), Fragment Based Drug Design and pro-drug design.

(LO3) To outline and plan Peptide synthesis, explain the role of protecting groups and combinatorial chemistry/ parallel synthesis approaches

(LO4) To outline the importance of natural product drug discovery and understanding of kinase inhibitor mechanism

(LO5) To critically evaluate industrial approaches used in structure property optimisation and the route redevelopment requirements when moving from a medicinal chemistry synthetic route to process and manufacturing of active pharmaceutical ingredients (API)

(S1) To be able to problem solve and the develop the ability to adapt and apply methodology to the solution of unfamiliar problems.

(S2) To develop communication skills through team working and face to face tutorials

(S3) To develop organisational skills and be able to analyse key data sets in medicinal chemistry.

Lectures. 25 x 1 hr. Selected lectures will have discussion points and questions which will be covered in following lectures.
Formative MCQ will be posted online in Canvas.

Coursework. Two assignments with marked work returned to students, supported by two feedback sessions (2 x 1 hr).

Workshops. 4 x 2 hr in-person workshops to support the lectures. The first will consist of a formative problem session. Workshops 2 and 3 will be used for assignment preparation and the fourth will be a revision problem session.

*Lectures: 25 hr
*Workshops: 8 hr
*Feedback sessions: 2 hr

•Introduction
Structures of Proteins: Bonds/ Energies Involved in Drug Receptor Interactions Introduction to Medicinal Chemistry (1 lecture).
Drug discovery and development (1 lecture)
Drugs and Treatment of Diseases (1 lecture)

•PK/PD
The Pharmaceutical, Pharmacokinetic and Pharmacodynamic Phases (1 lecture)
In vitro DMPK parameters for lead optimisation (2 lectures)

•Structure Activity Relationships
SAR and Fluorine Substitution in Medicinal Chemistry (2 lectures)
Quantitative Structure Activity Relationships (QSAR) (1 lecture)

•Drug Design
Ligand Efficiency and Lipophilic Ligand Efficiency (1 lecture)
Fragment Based Drug Discovery (2 lectures)

•Peptide Synthesis
Protecting Group Strategy in Synthesis (1 lecture)
Further mechanisms and problem solving in peptide synthesis (1 lecture)

•Industrial case studies
Structure property optimisation (2 lectures – Guest Lecturer)
Process chemistry (3 lectures – Guest Lecturer)

•Combinatorial Chemistry (2 lectures)

•Lipinski's Rules (1 lecture)

•Natural Products in Medicinal Chemistry (1 lecture)

•Kinase Drug Discovery (2 lectures)