Advanced methodologies in Medicinal Chemistry

A.Y. 2019/2020
8
Max ECTS
64
Overall hours
SSD
CHIM/08
Language
Italian
Learning objectives
Overall, the course represents the natural extension of the two basic courses of Medicinal and Toxicological Chemistry I and II. The main aims can be summarized as follows: (a) to further delve into the relevant features concerning the design, optimization and development of promising drug candidates; (b) to provide the bases to better understand both the development/evolution of innovative research fields (i.e., G protein-coupled receptors, photopharmacology, the role of chiral recognition in the design of bioactive molecules); (c) to furnish the theoretic bases and the main applications of the computational approaches to the rational drug design. By considering its professionalizing nature, the course aims at increasing the wealth of knowledge and the critical view with which the student should deal with research problems in the context of innovative drug design, being able to manage emerging theories and methods.
Expected learning outcomes
Knowledge and understanding. The course, which belongs to the main characterizing area of the whole master's degree, aims to ascertaining the student's knowledge of advanced approaches and methods in medchem sciences, intended to improve the basic skills in the medicinal chemistry field in view of her/his professional training.
Applying knowledge and understanding. During the exam, the student should be able to apply the new concepts and methods through the presentation and detailed discussion of scientific results published in the recent literature.
Making judgements. The student should be able to discuss with pertinence, awareness and criticism the topics chosen for the exam. For both course modules, correlations and comments pertaining to the medicinal chemistry research will be encouraged and evaluated by the teacher.
Communication. For both modules, exams involve the discussion, by means of a PowerPoint presentation, of a subject chosen among those illustrated during the lectures, which the student further develops by an independent bibliographic search. Clarity of presentation and communication skills are part of the overall evaluation.
Lifelong learning skills. The main objective of the course is that to ascertain the strengthening of the student's background in the medchem disciplines, by evaluating the acquirement of skills aiming to a professional figure able to work in the framework of academic/nonacademic institutions and in multidisciplinary projects.
Course syllabus and organization

Single session

Responsible
Lesson period
Second semester
Prerequisites for admission
For a fruitful attendance to the lessons, which take place in the second semester, the student should own the basic knowledge acquired in the two courses of Medicinal chemistry I and II. The student has to pass at least the exam of Medicinal chemistry I.
Assessment methods and Criteria
The exam consists in a discussion (25-30 min.) of a Power Point presentation, which deals with one of the topics illustrated in the classroom by each module. The student, which chooses the subject, has to further develop the related concepts by carrying out an autonomous bibliographic search. Before the exam, the teacher is available to evaluate the contents of the student's presentation and/or to examine the suitability of the related bibliographic references.
During the discussion, the quality and clarity of the presentation will be evaluated, together with the skills in illustrating the contents with an appropriate use of the scientific terminology, and the capacity of the student to answer to any elucidation requests from the teacher.
Marks of both modules are expressed out of thirty, and the final mark is the grade point average of module I and module II. In terms of registration of final marks, the agreed timing established by the Faculty of Pharmacy will be followed.
Advanced methodologies in Medicinal Chemistry I
Course syllabus
The course (4 credits) focuses on the following subjects.
a) G protein-coupled receptors (GPCRs): the new acquisitions on the structure and the mechanisms of signal transduction. The concept of allosteric modulation and of biased agonism of GPCRs will be illustrated together with the inherent therapeutic potential. Design, synthesis, biological evaluation and therapeutic implications of bitopic ligands and bi(poly)functional ligands acting on GPCRs (polypharmacology).
b) The drug discovery process, examined in a group of lectures given by researchers belonging to nonacademic scientific institutions. These lessons deal with the research and development of new drug candidates, mainly in the field of oncology (inhibitors of kinases and of PARP-1), from the idea to the initial design, to the enhancement of hit compound properties, and to the clinical development.
c) Design, synthesis, photochemical characterization, molecular targets, biological investigation and putative applications of new molecular probes, whose pharmacological activation is controlled by light (photopharmacology).
d) Study of the relevance of stereochemistry in the field of medicinal chemistry research (interaction with the biological target, synthetic and analytical aspects related to the preparation of chiral enantiopure ligands) and discussion of some strategies adopted by pharmaceutical companies for the synthesis of chiral drugs.
Teaching methods
The teaching methodology is that of collective frontal lessons (4 credits, 32 h).
The lessons aim at presenting advanced research topics in the field of medicinal chemistry. For the exam, the student will select one of the topics that he will further expand by searching for additional, pertinent reference articles and then organizing a presentation.
Teaching Resources
There are no recommended textbooks for the exam.
The slides, which contain a number of bibliographic references, are available as pdf files at the Ariel site of the course (https://mdeamicicft2.ariel.ctu.unimi.it/v5/home/Default.aspx).
Advanced methodologies in Medicinal Chemistry II
Course syllabus
The course covers the following computational topics: (a) conformational analysis: search of energy minima by stochastic techniques and molecular dynamics simulations; (b) molecular descriptors: methods for their calculation and applications in physicochemical profiling; (c) ligand-based approaches: QSAR and pharmacophore models; (d) protein structure and homology modeling; (e) structure-based approaches: molecular docking, virtual screening and MD-based simulations; (f) chemometric approaches and big data
Teaching methods
The teaching methodology is that of collective frontal lessons (4 credits, 32 h).
The lessons aim at presenting a detailed overview of the most relevant approaches which are tipically used in medicinal chemistry
Teaching Resources
There are no recommended textbooks for the exam.
The slides, plus a number of bibliographic references, are available as pdf files at the Ariel site of the course (https://gvistolimacf.ariel.ctu.unimi.it/v5/home/Default.aspx).
Advanced methodologies in Medicinal Chemistry I
CHIM/08 - PHARMACEUTICAL CHEMISTRY - University credits: 4
Lessons: 32 hours
Professor: De Amici Marco
Advanced methodologies in Medicinal Chemistry II
CHIM/08 - PHARMACEUTICAL CHEMISTRY - University credits: 4
Lessons: 32 hours
Professor: Vistoli Giulio