New Mansoura University Medicinal Chemistry Lecture 1 (Physico_LMS) PDF

New Mansoura University Faculty of Pharmacy Pharm D Program ___________________________________________________________________________ Department of Medicinal Chemistry Program: : Pharm D Program Course Title : Medicinal Chemistry-I...

New Mansoura University Faculty of Pharmacy Pharm D Program ___________________________________________________________________________ Department of Medicinal Chemistry Program: : Pharm D Program Course Title : Medicinal Chemistry-I Course Code: PMC-306 Course Code PMC-306 Lecturer Dr. Amal El-Masry Department Medicinal Chemistry Department Office Hrs Monday (9.0 AM – 3.0 PM) Course According to the By-law Description - Identify the principles of medicinal chemistry. - Recognizing the relationships between the chemical structures of different chemotherapeutic drugs and biological activities. - Understand the different mode of action of different classes of anticancer agents. Upon completing the course, the students will be able to dominate the following key elements: DOMAIN 1- FUNDAMENTAL KNOWLEDGE: Program K. Course K. element Course K. element element no. no. Recognize in-depth and breadth knowledge of medicinal chemistry course as one of the applied pharmaceutical sciences of the program and 1-1-1 1-1-1-1 manipulate these knowledge to provide information about drug production and proper use of drugs. Discuss the mode of action and therapeutic uses of chemotherapeutic agents 1-1-4 1-1-4-1 and anticancer drugs. DOMAIN 2: PROFESSIONAL AND ETHICAL PRACTICE: Program K. Course K. Course K. element element no. element no. Adapt the principles of medicinal chemistry to be applied in the systemic 2-1-6 2-1-6-1 approaches in drug development. Apply the given information from structural activity relationship to 2-2-1 2-2-1-1 evaluate the activity of related chemotherapeutic agents based on structural similarities and dissimilarities Apply the principles of bioinformatics and computer-aided tools and 2-2-3 2-2-3-1 molecular modeling programs in the design of new molecular entities. Detect the possible side effects and toxicity to a given drug molecule 2-4-3 2-4-3-1 based on its structural features. Utilize scientific principles of research and scholarly investigation and use 2-5-3 2-5-3-1 systematic approaches in the search for best available evidence. DOMAIN 3: PHARMACEUTICAL CARE: Program K. Course K. Course K. element element no. element no. Counsel the patients about proper use of antibiotics and prescribe therapeutic recommendations based on an understanding of drug 3-2-1 3-2-1-1 chemistry, pharmacodynamics, mechanisms of drug action and possible side effects and toxicity to a given drug molecule.  DOMAIN 4: PERSONAL PRACTICE: Program K. Course K. Course K. element element no. element no. Gather and analyse data, recognize problems independently and in participation 4-1-1 4-1-1-1 with other drug chemistry experts to solve these problems with demonstrating creativity and time management abilities. Participate autonomously and cooperatively in the offering of healthcare 4-1-2 4-1-2-1 services, beside contribution to the development of pharmacy knowledge or practices. Communicate effectively in a proper scientific language by verbal and written 4-2-1 4-2-1-1 means in the field of medicinal chemistry related to the studied topics. 4-2-2 4-2-2-1 Use artificial technologies to deliver useful information wherever feasible. Employ concepts of ongoing professional development, such as analyzing self- 4-3-2 4-3-2-1 learning needs and developing a strategy to achieve these needs.  Lectures Credit Hours Week Topics Hr(s) 1 Medicinal Chemistry Course Specification – Student Orientation 2 2 Introductory lecture - Physico-chemical properties of drug action 2 β-Lactam antibiotics (Penicillins, Part 1) 2 3 Newly approved drugs in this class (self-learning) 4 β-Lactam antibiotics (Penicillins, Part 2) + Case study + (Activity 1) 2 5 β-Lactam antibiotics (Cephalosporins) - Non-classical antibiotics 2 6 Macrolides + Tetracyclines 2 7 Sulfonamides and dihydrofolate reductase inhibitors + Aminoglycosides 2 8 - 9 Chloramphenicol + Antimycobacterial Agents + Antileprotics + Antiseptic agents 2 10 Anti-fungal agents (Part 1) + (Activity 2) 2 Anti-fungal agents (Part 2) + Case study 2 11 Newly approved drugs in this class (self-learning) Antiviral agents + Case study 12 2 Newly approved drugs in this class (self-learning) Antineoplastic Drugs 2 13 Newly approved drugs in this class (self-learning). 9 - Computer aided learning: a. Online learning b. Inter active discussion through LMS c. Power point (PPT) presentations - Self-learning - Formative assessment (Quizzes) - Class Activity/ Discussion / Brainstorming / Case study / Posters / Presentation  Methods To Assess Schedule Weighing To assess the ability of 1 Midterm Exam (MCQ) students to follow-up 8thweek 20 % course subjects To assess understanding 16th , 17th 2 Written Exam (Final , MCQ) 50 % and intellectual skills week Semester work (Activity 1 and 2) To assess understanding, 4th , 10th 3 [Personal/Team based learning intellectual and 30 % (TBL)] week transferable skills No Reference Type "Foye’s Principles of Medicinal Chemistry", 8th Edition, (David A. 1 Williams, Thomas L. Lemke & William O. Foye, Editors), Book Lippincott Williams & Wilkins, 2019. "Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry" 12th Edition, (J. H. Block and J. M. 2 Book Beale Jr, Editors), Lippincott Williams & Wilkins, Philadelphia, PA, 2011. "An Introduction to Medicinal Chemistry", 7th Revised Edition, 3 Book (Graham L. Patrick), Oxford University Press, USA, 2017. http://www.sciencedirect.com / http://www.google scholar.com / 4 websites http://www.pubmed.com https://www.ekb.eg  The term medicinal chemistry is devoted primarily to the Discovery, Development and Design of new agents to treat diseases. It is also concerned with Pharmacokinetics (ADME) (Absorption, Distribution, Metabolism and Excretion) Pharmacodynamics of drugs.  In very simple words, Medicinal Chemistry is the chemistry of drugs and it deals with: – Discovery, Development and Design of new agents for treating diseases. – Studying the mode of action (mechanism) – Studying the metabolism of drugs. – Studying the Structure Activity Relationship (SAR). It represents a link between chemistry and biology....  Pharmacokinetic Phase (ADME) It includes the time from the release of active principle till the drug reaches its site of action (receptor); it involves processes of. Absorption Distribution Metabolism Elimination  If the drug molecule is subjected to metabolic change by liver enzymes before reaching blood circulation, this is described as First pass effect  Pharmacodynamic phase It involves the interaction of the drug with its site of action (receptor). The ideal drug molecule will show favorable binding characteristics to the receptor. At the same time the drug will be expected to dissociate from the receptor and re-enter the systemic circulation to be metabolized and/or excreted, Why??. The above phases are controlled by The physicochemical properties of a drug. Pharmacodynamic phase  Medicinal Chemistry Structures Nomenclature Mode of Side effects action It deals Uses SAR with Analysis Synthesis Metabolism  The pharmacophore: – The pharmacophore; it is a structural unit in the drug which is essential for the interaction with the receptor. – On other words; it is the part of the molecule that contains the functional groups that actually binds to the receptor Structure-Activity Relationship (SAR): – The relationship between the chemical structure of a particular compound or a group of compounds and its (their) biological activity (How are new drugs discovered?).  Affinity: – The ability of the drug to interact with receptor (the extent of interaction). Or to measure of how strongly a drug binds to a receptor Intrinsic activity (efficacy): – The ability of the D-Receptor complex to produce biological effect.  The most important physicochemical properties that affect drug activity are the following:  Acid/base properties. Hydrophilic/lipophilic properties (Water and lipid solubility). Electronic effect of substituents. Steric effect of substituents. 1- Acid/Base Properties of Drugs  1- Acid/Base Properties of Drugs Most of drugs are of a weak acidic or weak basic nature, thus the Bronsted-Lowery acid/base theory is most appropriate for explaining and predicting acid/base behavior of drugs. Acidic functional groups are those capable of donating protons. Basic functional groups are those capable of accepting protons.  1- Acid/Base Properties of Drugs Acidic drug (AH) Basic drug (B) HA + H2O A- + H3O+ B + H 2O BH+ + OH- + R-COOH R-COO- R-NH2 R-NH3 2-Hydrophilic/lipophilic properties (Water and lipid solubility)  In a drug structure:- – Hetero-atoms and functional groups capable of forming H-bond and ionized bonds with water molecules represent the water soluble or hydrophilic part. – While carbon skeleton represents the lipophilic or water insoluble part. – Halogen atoms as F, Cl, Br or I are incapable to form any bonding with water molecules. Electron withdrawing groups as NO2 or electronegative group or atom as Cl or CF3 will decrease the electron density on the carboxylate ion so stabilize the ionized form of benzoic acid and thus, the acidity increases. Charge is stabilised by X → Equilibrium shifts to right  Pharmacokinetic Phase (ADME) Absorption Distribution Metabolism Elimination Structures Nomenclature Pharmacodynamic phase Side effects Mode of action It involves the interaction of It deals the drug with its site of action Uses SAR (receptor). with Analysis Synthesis Metabolism Acid/Base Properties of Drugs Hydrophilic/lipophilic properties Acidic drug (AH) HA + H2O A- + H3O+ R-COOH R-COO- Basic drug (B) Steric and electronic effect of substituents B + H 2O BH+ + OH- R-NH2 R-NH3 37  Choose the correct answer: Which of the following terms is the measure of how strongly a drug binds to a receptor?  Give the scientific name: It is a structural unit in the drug which is essential for the interaction with the receptor. (…………………………..)