Medicinal Chemistry 2

A.Y. 2020/2021
10
Max ECTS
80
Overall hours
SSD
CHIM/08
Language
Italian
Learning objectives
The course aims at providing the most relevant concepts related to the design, synthesis, physico-chemical and stereo-electronic properties, mechanism of action, therapeutic application and side effects of the drugs belonging to the investigated classes. In particular, lectures will deal with the structure-activity relationships and the approaches applied in medicinal chemistry to optimize the pharmacodynamic profile and the pharmacokinetic properties of drugs. Based on the fundamentals acquired in the course of Medicinal and Toxicological Chemistry 1, in the present course the student should accomplish a good overall background in medicinal chemistry, through the study of drugs acting on the central and peripheral nervous system, the cardiovascular and anti-histamine drugs, the non-steroidal anti-inflammatory agents.
Expected learning outcomes
Expected learning outcomes (nuovo testo da inserire in W4)
Knowledge and understanding. The course aims to ascertaining the student's knowledge of the approaches and methods presented during the lectures, particularly those related to the structural aspects of drugs, their genesis and their therapeutic classification.
Applying knowledge and understanding. During the exam, the student should be able to apply knowledge and understanding, in particular by appropriately discussing the main aspects of the structure/synthesis of the main compounds of a class of drugs, together with their related therapeutic utility.
Making judgements. The student will answer any question with pertinence and criticism, both in the written and oral part of the exam. In their answers, students are frequently requested to motivate their own choices.
Communication. During the exam, the student will demonstrate to explain and develop concepts with clarity, synthesis and language skills. 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 Medicinal Chemistry: the acquired competence will help the student's informed choice (professionalizing courses/thesis lab) towards completing the educational path.
Course syllabus and organization

Single session

Responsible
Lesson period
year
Didactic methods
Lessons scheduled for the first semester will be held remotely and synchronously by means of the MS Teams platform. In the second semester, if allowed by the regulations on social distancing, part of the lessons (about 50%) will be held in person. However, all lessons will be available remotely through the MS Teams platform. Attendance to the lessons on site will be regulated by a communication published on the course pages of the Ariel Platform. Students should regularly refer to the Ariel platform, particularly during the emergency phase. The recorded lessons and the related didactic material (slides as pdf files) will be made available on the Ariel Platform, to allow their use also in the asynchronous mode.

Program and reference material
The program and reference material will not be modified.

Methods for verification of learning and evaluation criteria
As in the past, the examination will take place in written form. If allowed by the regulations, the exams will be held in person, in accordance with the security rules. Students unable to reach the University due to reasons related to the Covid-19 emergency, will be allowed to take the exam remotely, possibly on a different day. The modality of the written exam is similar to that of "standard exam sessions", consisting of open-ended questions (usually three for each exam). Corrections and comments will be available through the MS Teams platform following an appointment with the teacher. Supplementary oral exams as well as midterm exams are not at present planned.
In case the exams will not be allowed on site, due to the emergency situation, they will be performed remotely on the MS Teams platform (see also the University portal at https://www.unimi.it/en/study/bachelor-and-master-study/following-your-…), with the same above reported modality. The enrolled students will receive all the necessary information through e-mail.
Course syllabus
The course program (10 credits) focuses on the study of biomolecular processes involving neurotransmitters, neuromodulators and second messengers and on the investigation of the structural features (stereo-electronic requirements, topology, topography, conformational equilibria and acid-base properties) of drugs (ligands) interacting with the main biological targets (receptors, enzymes, channels).
The main medicinal chemistry aspects under study include the structural modifications of biologically active natural compounds, the modification of molecular portions of "lead compounds" and their impact on the affinity-activity-selectivity-bioavailability profiles, the discussion of the synthetic strategies of relevant active principles, the new acquirements about the mode of action of drugs and their impact on therapeutic applications.
Based on the above-cited guidelines, the course defines and discusses the following classes of drugs.
a) Drugs influencing the parasympathetic neurotransmission (drugs active on nicotinic or muscarinic receptors, cholinesterase inhibitors) as well as the orthosympathetic neurotransmission (drugs active on alpha- and beta- adrenergic receptors, MAO inhibitors and COMT inhibitors).
b) Drugs of the central nervous system (anesthetics, anxiolytic and sedative-hypnotic drugs, anticonvulsants, antiparkinsonian drugs, opioid analgesics, antipsycothic drugs, antidepressants, hallucinogenic drugs and related substances of abuse).
c) Drugs of the cardiovascular system (cardioactive glycosides, antianginal drugs, antiarrhythmic drugs, calcium channels blockers, potassium channels activators, ACE-inhibitors, angiotensin antagonists, diuretics).
d) Nonsteroidal anti-inflammatory drugs.
e) Antihistaminic agents, anti-allergic and anti-ulcer drugs.
Prerequisites for admission
For a fruitful attendance to the lessons, which take place all year long, the student should own the knowledge acquired in the courses of Organic chemistry and Medicinal and toxicological chemistry 1. To take the exam, the student must pass the exams of Medicinal and toxicological chemistry 1 as well as of Organic chemistry 2.
Teaching methods
The teaching modality is that of collective frontal lessons (10 credits, 80 h).
Teaching Resources
The slides presented in the classroom are available as pdf files on the Ariel site of the course (https://mdeamicicft2.ariel.ctu.unimi.it/v5/home/Default.aspx).
For a further deepening of the topics, the following textbooks are recommended.
A) T. L. Lemke, D. A. Williams: "Foye's Principi di Chimica Farmaceutica", Piccin - Nuova Libraria Editore, 6a edizione italiana (2014).
B) G. L. Patrick: "Introduzione alla Chimica Farmaceutica", EdiSES, edizione integrata (2015).
C) Monografie della Collana "Chimica dei Recettori", C. Melchiorre Editore, CLUEB (Bologna).
D) "Chimica Farmaceutica", 1a edizione italiana, A. Gasco, F. Gualtieri, C. Melchiorre Editori, Casa Editrice Ambrosiana (2015).
E) "Goodman & Gilman's. The Pharmacological Basis of Therapeutics" Thirteenth Edition, McGraw-Hill Education (2018).
F) "Farmacologia Generale e Molecolare", F. Clementi, G. Fumagalli Editori, 4a edizione, EDRA (2016).
Assessment methods and Criteria
The students attending the whole course have the opportunity, subject to checking their presence to the lessons, to take "two written midterm exams" (about 2.5 h each). These exams, which are scheduled each academic year on February and July, focus on the first and second semester program, respectively. They consist of open-ended questions (usually four for each exam), including, for a given drug, a comment on its structure (that the students will find in the text or should draw) with the main structure-activity relationships. Then, a discussion on the mechanism of action, the therapeutic class and side effects, the physicochemical properties and the synthetic approaches. The overall evaluation takes into account the student's ability to organize answers to all questions, the quality and clarity of presentation and the language used. To pass the exam, the student should reach a sufficient evaluation in each of the two tests: the final mark is expressed out of thirty (from 18/30 to 30/30 cum laude), and is the grade point average of the two marks. No oral exams are planned for this exam modality.
As in the case of standard exam sessions, mark registration of the exam is subject to passing exams of both Medicinal and toxicological chemistry 1 and Organic chemistry 2.
The "standard exam sessions" consist of a written exam (about 2.5 h) on the entire program, with four open-ended questions as specified above. To pass the written exam, at least three out of four of the student's answers must be sufficient. Students with a positive evaluation will take the oral part of the exam, during which, in addition to the discussion on the answers given in their written exam, they will answer to two/three further questions on other topics of the program. The final mark is expressed out of thirty (see above), and the evaluation of the written exam has a determinant role. The results on the written exam evaluation are communicated to the students within two weeks, concurrently with the oral exam. The students failing written exams must sign up for the next exam session. Written exams may be taken in consecutive sessions without any restrictions. Exam sessions, at least six per year, are in accordance with the indications from the Faculty of Pharmacy.
CHIM/08 - PHARMACEUTICAL CHEMISTRY - University credits: 10
Lessons: 80 hours
Professor: De Amici Marco
Professor(s)