《Medicinal Chemistry》课程教学大纲 一、课程基本信息 英文名称 Medicinal Chemistry 课程代码 PHAR1169 课程性质 专业必修课程 授课对象 药学全英文班 学 分 4 学 时 72 主讲教师 乔春华、叶娜、仇晓琰、龙亚秋 修订日期 2021.7.27 指定教材 Foye's Principles of Medicinal Chemistry,7thedition 二、课程目标 Overall objective: Medicianl Chemistry is a course to introduce the drugs used in the clinic.The objective of this course is to teach students the basic aspects of drugs,including drug discovery,development,property,preparation,mechanism ofaction,side effect,metabolism et al. Students are required to master the most prescribed drugs,recognize the pharmaceuticals,pharmacophores,mechanism of action,drug metabolism,major side effect,synthetic method for some drugs,drug development. The following drug indication areas are covered:central nerve system,cardiovascular system,immune system,hormonal systems, endocrine system,inflammatory system,drugs used as chemotherapeutic agents,including:cancer and infectious disease.The students are expected to master the basic aspects of the lectured drugs
《Medicinal Chemistry》课程教学大纲 一、课程基本信息 英文名称 Medicinal Chemistry 课程代码 PHAR1169 课程性质 专业必修课程 授课对象 药学全英文班 学 分 4 学 时 72 主讲教师 乔春华、叶娜、仇晓琰、龙亚秋 修订日期 2021.7.27 指定教材 Foye’s Principles of Medicinal Chemistry, 7th edition 二、课程目标 Overall objective： Medicianl Chemistry is a course to introduce the drugs used in the clinic. The objective of this course is to teach students the basic aspects of drugs, including drug discovery, development, property, preparation, mechanism of action, side effect, metabolism et al. Students are required to master the most prescribed drugs, recognize the pharmaceuticals, pharmacophores, mechanism of action, drug metabolism, major side effect, synthetic method for some drugs, drug development. The following drug indication areas are covered: central nerve system, cardiovascular system, immune system, hormonal systems, endocrine system, inflammatory system, drugs used as chemotherapeutic agents, including: cancer and infectious disease. The students are expected to master the basic aspects of the lectured drugs
Specific teaching aims for each section/chapter are closely related to the teaching contents,which are provided and detailed in the teaching content section (Objectives for each section: Section 1:Principles of Drug Discovery 1.Drug discovery from natural products Natural products provide a rich source of clinical used drugs,especially before 1980s.The isolated small molecules from plant,animal,mircrobe,or mineral origin present structural diversity and biological activity diversity of organic compounds,and inspire the later drug discovery process. In this chapter,the students are required to master several basic concepts:the definition of medicinal chemistry,the definition of natural products,drug target,the pharmacophore,the lead compounds,the drug-like properties. the students are required to get a knowledge or understand:the history and evolution of medicinal chemistry,why are natural products important for drug discovery,the isolation and identification of natural products,case studies of several classic clinic drugs directly from natural origin or derived from natural products,the innovative drug discovery process,approaches to find a lead. 1.2 Drug design and relationship of functional groups to pharmacologic activity Medicinal chemistry studies how chemical structure influences biologic activity.As such,it is necessary to understand not only the mechanism by which a drug exerts its effect,but also how the molecular and physicochemical properties of the molecule influence the drug's pharmacokinetics (absorption,distribution,metabolism,toxicity,and elimination)and pharmacodynamics(what the drug does to the body). In this chapter,the students are required to master basic concepts:the definition of physicochemical properties,the definition of structure and activity relationship,structure and pharmacokinetics relationship,structure and toxicity relationship;the concept and measurement of Ionization,Lipophilicity,Hydrogen bond ing,stereochemistry;the definition of bioisostere and classifications. the students are required to get a knowledge or understand:how the structures determine the physicochemical properties and how the physicochemical properties affect the ADMET?How to design a drug?The theory and the examples on the drug design:how to find a hit,SAR and lead,lead optimization,Structure Modification:Bioisostere. 1.3 Receptors as targets for drug discovery
Specific teaching aims for each section/chapter are closely related to the teaching contents, which are provided and detailed in the teaching content section （二）Objectives for each section： Section 1：Principles of Drug Discovery 1. Drug discovery from natural products Natural products provide a rich source of clinical used drugs, especially before 1980s. The isolated small molecules from plant, animal, mircrobe, or mineral origin present structural diversity and biological activity diversity of organic compounds, and inspire the later drug discovery process. In this chapter, the students are required to master several basic concepts: the definition of medicinal chemistry, the definition of natural products, drug target, the pharmacophore, the lead compounds, the drug-like properties. the students are required to get a knowledge or understand: the history and evolution of medicinal chemistry, why are natural products important for drug discovery, the isolation and identification of natural products, case studies of several classic clinic drugs directly from natural origin or derived from natural products, the innovative drug discovery process, approaches to find a lead. 1.2 Drug design and relationship of functional groups to pharmacologic activity Medicinal chemistry studies how chemical structure influences biologic activity. As such, it is necessary to understand not only the mechanism by which a drug exerts its effect, but also how the molecular and physicochemical properties of the molecule influence the drug’s pharmacokinetics (absorption, distribution, metabolism, toxicity, and elimination) and pharmacodynamics (what the drug does to the body). In this chapter, the students are required to master basic concepts: the definition of physicochemical properties, the definition of structure and activity relationship, structure and pharmacokinetics relationship, structure and toxicity relationship; the concept and measurement of Ionization, Lipophilicity, Hydrogen bonding, stereochemistry; the definition of bioisostere and classifications. the students are required to get a knowledge or understand: how the structures determine the physicochemical properties and how the physicochemical properties affect the ADMET? How to design a drug? The theory and the examples on the drug design: how to find a hit, SAR and lead, lead optimization, Structure Modification: Bioisostere. 1.3 Receptors as targets for drug discovery
Drugs exert their therapeutic effects by interacting with those proteins within the body which are crucial for the disease.Paul Ehrlich,a noted microbiologist during the late 19th and early 20th centuries,is credited with coining the term "receptive substance," or"receptor."He also proposed that the interaction or binding of the drug with the receptor was analogous to a"lock"(the receptor) and a"key"(the drug),which gave rise to the lock and key fit theory for drug receptors.Receptor are proteins which are,by far the most important drug targets in medicine.They are implicated in ailment such as pain,depression,Parkinson's disease,psychosis,heart failure,asthma,etc.and account for 40%drugs used today. In this chapter,the students are required to master basic concepts:the drug targets,the receptor and its classification,the ligand, the structure and function of 4 major classes of drug receptors,the receptor interactions:affinity,potency,efficacy,the agonist,the antagonist,Determination of Affinity:the role of chemical bonding,the role of conformation,the role of stereochemistry. the students are required to get a knowledge or understand:how to define and determine Potency and Efficacy of receptors, agonist types,dose-response curve,Orthosteric and Allosteric Antagonist,voltage-gated and ligand-gated ion-channels,GPCR, transmembrane catalytic receptor,cytoplasmic or nuclear receptor;GPCR Signal Transduction;the GPCR Assays in the Lab;case study of several receptor antagonist or agonist as therapeutic agents. 1.4 Drug discovery through enzyme inhibition Enzymes are specialized proteins that function as catalysts to increase the rate of biochemical reactions.By interacting with substrates (reactant molecules upon which an enzyme acts),enzymes catalyze chemical reactions involved in the biosynthesis of many cellular products.The body is composed of thousands of different enzymes,many of them acting in concert to maintain homeostasis. Although disease states may arise from the malfunctioning of a particular enzyme,or the introduction of a foreign enzyme through infection by microorganisms,inhibiting a specific enzyme to alleviate a disease state is a challenging process but turn out very effective therapeutics.Enzymes are the targets for 30-40%of all drugs used today. In this chapter,the students are required to master basic concepts:enzymes as catalytic proteins and general concepts of enzyme inhibitors and their rational design into drugs,the structure and function of enzymes,the enzyme kinetics,covalent catalysis, Lineweaver-Burk plot of 1/v versus 1/[S]and the key parameters,enzyme inhibitor design strategy,irreversible enzyme inhibitor the students are required to get a knowledge or understand:the naming of enzymes,the mechanism of the enzyme catalysis, Enzyme Inhibitors:Competitive and noncompetitive,reversible and irreversible,case study of typical enzyme inhibitor designs, mechanism and evolution of covalent enzyme inhibitors. Section 2:Drug receptors affecting neurotransmission and enzymes as catalytic receptors
Drugs exert their therapeutic effects by interacting with those proteins within the body which are crucial for the disease. Paul Ehrlich, a noted microbiologist during the late 19th and early 20th centuries, is credited with coining the term “receptive substance,” or “receptor.” He also proposed that the interaction or binding of the drug with the receptor was analogous to a “lock” (the receptor) and a “key” (the drug), which gave rise to the lock and key fit theory for drug receptors. Receptor are proteins which are, by far the most important drug targets in medicine. They are implicated in ailment such as pain, depression, Parkinson’s disease, psychosis, heart failure, asthma, etc. and account for 40% drugs used today. In this chapter, the students are required to master basic concepts: the drug targets, the receptor and its classification, the ligand, the structure and function of 4 major classes of drug receptors, the receptor interactions: affinity, potency, efficacy, the agonist, the antagonist, Determination of Affinity: the role of chemical bonding, the role of conformation, the role of stereochemistry. the students are required to get a knowledge or understand: how to define and determine Potency and Efficacy of receptors, agonist types, dose-response curve, Orthosteric and Allosteric Antagonist, voltage-gated and ligand-gated ion-channels, GPCR, transmembrane catalytic receptor, cytoplasmic or nuclear receptor;GPCR Signal Transduction; the GPCR Assays in the Lab; case study of several receptor antagonist or agonist as therapeutic agents. 1.4 Drug discovery through enzyme inhibition Enzymes are specialized proteins that function as catalysts to increase the rate of biochemical reactions. By interacting with substrates (reactant molecules upon which an enzyme acts), enzymes catalyze chemical reactions involved in the biosynthesis of many cellular products. The body is composed of thousands of different enzymes, many of them acting in concert to maintain homeostasis. Although disease states may arise from the malfunctioning of a particular enzyme, or the introduction of a foreign enzyme through infection by microorganisms, inhibiting a specific enzyme to alleviate a disease state is a challenging process but turn out very effective therapeutics. Enzymes are the targets for 30-40% of all drugs used today. In this chapter, the students are required to master basic concepts: enzymes as catalytic proteins and general concepts of enzyme inhibitors and their rational design into drugs, the structure and function of enzymes, the enzyme kinetics, covalent catalysis, Lineweaver-Burk plot of 1/v versus 1/[S] and the key parameters, enzyme inhibitor design strategy, irreversible enzyme inhibitor the students are required to get a knowledge or understand: the naming of enzymes, the mechanism of the enzyme catalysis, Enzyme Inhibitors: Competitive and noncompetitive, reversible and irreversible, case study of typical enzyme inhibitor designs, mechanism and evolution of covalent enzyme inhibitors. Section 2：Drug receptors affecting neurotransmission and enzymes as catalytic receptors
2.1 Drugs affecting cholinergic neurotransmission Get a general idea about acetylcholine and cholinergic receptors;Understand the development history of drugs affecting cholinergic neurotransmission;To master the chemical structures,drug design,structure-activity relationships,and mechanism of actions of major drugs affecting cholinergic neurotransmission;Understand the synthesis and metabolism of major drugs affect ing cholinergic neurotransmission 2.2 Adrenergic Receptors and Drugs Affecting Adrenergic Neurotransmission Get a general idea about adrenaline and adrenergic receptors;Understand the development history of drugs affecting adrenergic neurotransmission;To master the chemical structures,drug design,structure-activity relationships,and mechanism of actions of major drugs affecting adrenergic neurotransmission;Understand the synthesis and metabolism of major drugs affecting adrenergic neurotransmission 2.3 Serotonin receptors and Drugs Affecting Serotonergic Neurotransmission Get a general idea about serotonin and serotonergic receptors;Understand the development history of drugs affecting serotonergic neurotransmission;To master the chemical structures,drug design,structure-activity relationships,and mechanism of actions of major drugs affecting serotonergic neurotransmission;Understand the synthesis and metabolism of major drugs affecting serotonergic neurotransmission 3.1Drugs Used to Treat Neuromuscular Disorders:Antiparkinsonian Agents Get a general idea about Parkinson'diseases,Understand the development history of antiparkinsonian drugs;To master the chemical structures,drug design,structure-activity relationships,and mechanism of actions of major antiparkinsonian drugs; Understand the synthesis and metabolism of antiparkinsonian drugs. 3.2 Antipsychotic Drugs Get a general idea about Mental illnesses;Understand the development history of antipsychotic drugs;To master the chemical structures,drug design,structure-activity relationships,and mechanism of actions of major antipsychotic drugs;Understand the synthesis and metabolism of antipsychotic drugs. 3.3 Sedative-Hypnotics
2.1 Drugs affecting cholinergic neurotransmission Get a general idea about acetylcholine and cholinergic receptors; Understand the development history of drugs affecting cholinergic neurotransmission; To master the chemical structures, drug design, structure-activity relationships, and mechanism of actions of major drugs affecting cholinergic neurotransmission; Understand the synthesis and metabolism of major drugs affecting cholinergic neurotransmission 2.2 Adrenergic Receptors and Drugs Affecting Adrenergic Neurotransmission Get a general idea about adrenaline and adrenergic receptors; Understand the development history of drugs affecting adrenergic neurotransmission; To master the chemical structures, drug design, structure-activity relationships, and mechanism of actions of major drugs affecting adrenergic neurotransmission; Understand the synthesis and metabolism of major drugs affecting adrenergic neurotransmission 2.3 Serotonin receptors and Drugs Affecting Serotonergic Neurotransmission Get a general idea about serotonin and serotonergic receptors; Understand the development history of drugs affecting serotonergic neurotransmission; To master the chemical structures, drug design, structure-activity relationships, and mechanism of actions of major drugs affecting serotonergic neurotransmission; Understand the synthesis and metabolism of major drugs affecting serotonergic neurotransmission 3.1Drugs Used to Treat Neuromuscular Disorders: Antiparkinsonian Agents Get a general idea about Parkinson’diseases, Understand the development history of antiparkinsonian drugs; To master the chemical structures, drug design, structure-activity relationships, and mechanism of actions of major antiparkinsonian drugs; Understand the synthesis and metabolism of antiparkinsonian drugs. 3.2 Antipsychotic Drugs Get a general idea about Mental illnesses; Understand the development history of antipsychotic drugs; To master the chemical structures, drug design, structure-activity relationships, and mechanism of actions of major antipsychotic drugs; Understand the synthesis and metabolism of antipsychotic drugs. 3.3 Sedative-Hypnotics
Get a general idea about anxiety and insomnia.Understand the development history of anxiolytics and sedative-hypnotics.To master the chemical structures,drug design,structure-activity relationships,and mechanism of actions of major anxiolytics and sedative-hypnotics;Understand the synthesis and metabolism of anxiolytics and sedative-hypnotics. 3.3 Anti-seizure Master the two seizure related neurotransmitters:GABA and Glutamate,their structure and biological function;Anti-seizure drug mechanism:through enhancing GABA function or inhibit glutamate function;Be able to draw the structures for major drugs for the treatment of seizure 3.4 Anti-depressant Two neurotransmitters are closely related to this chapter:serotonin(5-HT),norepinephrine (NE),and Dopamine.Anti- dedepressant drugs can be classified based on their mechanism of action:(1)selective serotonin reuptake inhibitors: (2)selective norepinephrine reuptake inhibitors;(3)norepinephrine and serotonin reuptake inhibitors;(4)dopamine and norepinephrine reuptake inhibitors;(5)monoamine oxidase inhibitors.The most prescribed drugs for the treatment of depression: Venlafaxine,Duloxetine,fluoxetine,Citalopram;structural feature and development,mechanism of actions of these drugs. 3.5 Central analgesics Natural product(Morphine)and synthetic analgesics(Flexible u agonists,fentanyl)are the two type of drug used in the clinic. Mechanism of action of these central analgesics,u receptor agonist;pharmacophores of morphine and fentanyl drugs Side effect of central analgesics:addiction,respiratory repression and cross tolerance are the most undesired side effect. Specific drugs in this chapter:Morphine,Hydromorphone,Codeine,Heroin;Fentanyl,Sufentanil,Alfentanil,Methadone. Codeine and Heroin metabolism Chemotherapeutic agents: 7.1 Antibiotics and antimicrobial agents Master the following types ofdrugs,their structures,mechanism of action,metabolism,side effects.(1)sulfonamides; (2)Quinolones(1-4 generation),pharmacophores for Quinolones;(3)B-lactams:penicillin and Cephalosporins;(4)Aminoglycosides; (5)Macrolides;(6)Rifamycin Antibiotics;(7)Tetracyclines
Get a general idea about anxiety and insomnia. Understand the development history of anxiolytics and sedative-hypnotics. To master the chemical structures, drug design, structure-activity relationships, and mechanism of actions of major anxiolytics and sedative-hypnotics; Understand the synthesis and metabolism of anxiolytics and sedative-hypnotics. 3.3 Anti-seizure Master the two seizure related neurotransmitters: GABA and Glutamate, their structure and biological function; Anti-seizure drug mechanism: through enhancing GABA function or inhibit glutamate function; Be able to draw the structures for major drugs for the treatment of seizure. 3.4 Anti-depressant Two neurotransmitters are closely related to this chapter: serotonin(5-HT), norepinephrine (NE), and Dopamine. Antidedepressant drugs can be classified based on their mechanism of action: (1) selective serotonin reuptake inhibitors; (2) selective norepinephrine reuptake inhibitors;(3) norepinephrine and serotonin reuptake inhibitors; (4) dopamine and norepinephrine reuptake inhibitors; (5) monoamine oxidase inhibitors. The most prescribed drugs for the treatment of depression: Venlafaxine, Duloxetine, fluoxetine, Citalopram; structural feature and development, mechanism of actions of these drugs. 3.5 Central analgesics Natural product (Morphine) and synthetic analgesics (Flexible µ agonists, fentanyl) are the two type of drug used in the clinic. Mechanism of action of these central analgesics, µ receptor agonist; pharmacophores of morphine and fentanyl drugs. Side effect of central analgesics: addiction, respiratory repression and cross tolerance are the most undesired side effect. Specific drugs in this chapter: Morphine, Hydromorphone, Codeine, Heroin; Fentanyl, Sufentanil, Alfentanil, Methadone. Codeine and Heroin metabolism Chemotherapeutic agents: 7.1 Antibiotics and antimicrobial agents Master the following types of drugs, their structures, mechanism of action, metabolism, side effects. (1) sulfonamides; (2) Quinolones (1-4 generation), pharmacophores for Quinolones; (3) β-lactams: penicillin and Cephalosporins; (4) Aminoglycosides; (5) Macrolides; (6) Rifamycin Antibiotics; (7) Tetracyclines