《Medicinal Chemistry》课程教学大纲

一、课程基本信息

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

（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

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 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

The most prescribed antibiotic: quinolones and cephalosporins.

Combination use: cephalosporins along with lactamase inhibitors

7.2 Antifungal agents

Master the most important antifungal drug is the triazole class, which target the fungal membrane ergosterol biosynthesis. Along this synthesis pathway, there are four drug target enzymes: the squalene oxidase, lanosterol, Δ¹⁴-reductase, Δ⁸, Δ⁷-isomerase. The 2^nd most prescribed drug class is the polyene and the other widely used antifungal drug in the clinic is the Echinocandins; Update antifungal drug development.

Structural feature of the azole drugs, specific mechanism of action, selectivity of these drugs.

7.3 Antimycobacterial agents

Master the four first-line anti-TB drugs: isoniazid, ethambutol, Pyrazinamide, Rifamycin. Understand their mechanism of action, recognize the molecules when provided.

Updated anti-TB drugs developed after 2000: the nitro-imidazole type, Bedaquiline

The second line anti-TB drug: Streptomycin and the 4^th generation quinolones

7.4 Cancer and chemotherapy

Cancer chemotherapy drug type: (1) alkylating agents; (2) Organoplatinum complexes; (3) Antimetabolites; (4) DNA Polymerase/DNA Chain Elongation Inhibitors; (5) Mitosis Inhibitor taxol; (6) Kinase inhibitors; (7) epigenetic drugs.

Students are required to master the major drugs in each class, drug pharmacophore, mechanism of action, side effects.

7.5 Antiviral agents

Master drugs used for the treatment of influenza (Neuramidase inhibitor), HIV, HCV;

Conventional Nucleoside Analogs, specific purine and pyrimidine analogs as anti-viral drugs;  

1. Nucleoside Reverse Transcriptase Inhibitor (NRTIs) as anti-HIV drugs; specific drugs: AZT, ABC, et al; (2) protease inhibitors as anti-viral drugs; (3) Integrase inhibitors as anti-viral drugs. Specific drugs include: Elvitegravir, Dolutegravir, Bictegravir.

HCV drug development after 2010: Nonstructural protein 5B (NS5B): NS5B; NS3/4A Protease inhibitors; specific drugs: sofosbuvir, Telaprevir, Bocsprevir

（三）课程目标与毕业要求、课程内容的对应关系

表1：课程目标与课程内容、毕业要求的对应关系表

三、教学内容

Section 1. Principles of drug discovery

1.教学目标

 Define the medicinal chemistry, pharmacy, pharmaceutics and pharmacopoeia, the contents of pharmaceutical care; the drug discovery process, the drug design strategy, the drug targets and the bioassay, the SAR/SPKR/STR; ethical code for pharmaceutical researchers, understand the regulations and laws related to drug administration.

2.教学重难点

The natural product-based drug discovery, the rational drug design by manipulating the physicochemical properties of the lead, targets (enzyme and receptor) structure and function, the receptor function, affinity and potency and efficacy, the mechanism of enzyme catalysis, the approaches to find a lead and structural optimization, the SAR, SPKR, STR, case studies for the natural product drug, receptor antagonist drug, receptor agonist drug, enzyme inhibitor drug.

3.教学内容

1. Drug discovery from natural products

to master basic concepts: the definition of medicinal chemistry, the definition of natural products, drug target, the pharmacophore, the lead compounds, the drug-like properties.

To have a general idea 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

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.

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

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

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

 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 discovery and development, mechanism and evolution of covalent enzyme inhibitors.

 4.教学方法

(1) Teaching method: Relevant concepts and theoretical framework.

(2) Discussion method: The use of heuristic teaching.

5.教学评价

Quick summary test and discuss selected frequently asked questions.

Section 2. Drugs receptors affecting neurotransmission and enzymes as catalytic receptors

2.1 Drugs affecting cholinergic neurotransmission

 Get a general idea about neurotransmitters and associated neuropsychiatric disease; Get a general idea about acetylcholine and its functions and neurochemistry, and the distribution, structures and functions of cholinergic receptors. Get a general idea about Alzheimer disease.

 Understand the development history of cholinergic drugs.

 To master the chemical structures, drug design, structure-activity relationships, and mechanism of actions of major cholinergic drugs; Understand the synthesis and metabolism of major cholinergic drugs

Including the following specific drugs:

 Muscarinic Agonists: Methacholine Chloride; Carbachol; Bethanechol Chloride; Pilocarpine; Cevimeline

 Acetylcholinesterase Inhibitors: Neostigmine; Rivastigmine; Tacrine; Galantamine; Donepezil;

 Muscarinic Antagonists: Atropine and its Analogues; Tiotropium bromide; Artane; Benztropine.

2.2 Adrenergic Receptors and Drugs Affecting Adrenergic Neurotransmission

 Get a general idea about adrenaline and its functions and neurochemistry, and the distribution, structures and functions of norepinephrine receptor.

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

Including the following specific drugs:

 Alpha1 Adrenergic Agonists: Phenylethanolamines; 2-Arylimidazolines

 Alpha2 Adrenergic Agonists: 2-Aminoimidazolines (e.g. Clonidine)

 Beta1 Adrenergic Agonists: Dobutamine

 Beta2 Adrenergic Agonists: Phenylethanolamines (e.g. Isoproterenol; albuterol, salmeterol)

 Alpha1 Adrenergic Antagonists: Prazosin

 Beta Adrenergic Antagonists: aryloxypropanolamines (e.g. Propranolol; Metoprolol)

2.3 Serotonin receptors and Drugs Affecting Serotonergic Neurotransmission

 Get a general idea about serotonin and its functions and neurochemistry, and the distribution, structures and functions of serotonin receptor.

 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

Including the following specific drugs:

 5-HT1A Receptor Agonists: Buspirone, gepirone, ipsapirone; Vilazodone

 5-HT1D Agonists: Sumatriptan

 5-HT1F Agonists: Lasmiditan

Selective inverse 5-HT2A agonist: pimavanserin

5-HT2B agonist: fenfluramine/phentermine

5-HT2C agonist: lorcaserin

5-HT2C antagonist: Agomelatine

5-HT-3 Receptor Antagonists: Ondansetron

Section 3 Drugs affecting central nervous system

3.1 教学目标

Get a general idea about Parkinson’diseases, Get a general idea about dopamine and its functions and neurochemistry, and the distribution, structures and functions of dopamine receptor.

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 教学重难点

Drug discovery and design, chemical structures, structure-activity relationships, and mechanism of actions of major drugs affecting central nervous system

3.3.教学内容

3.3.1Drugs Used to Treat Neuromuscular Disorders: Antiparkinsonian Agents

Including the following specific drugs:

Dopamine replacement: L-DOPA, carbidopa, Tolcapone, Selegiline,Rasagiline; Safinamide

Dopamine Receptor Agonists: apomorphine, pramipexole, ropinirole

Drugs Indirectly Target Dopamine System: Amantadine, Artane, Rivastigmine, Istradefylline

3.3.2 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.

Including the following specific drugs:

First Generation Antipsychotics: Chlorpromazine, Thioxanthenes, Haloperidol

Second Generation Antipsychotics: Clozapine, olanzapine, quetiapine,

Third Generation Antipsychotics: Ziprasidone, Lurasidone, Risperidone, Paliperidone, Aripiprazole, Cariprazine, Brexpiprazole

3.3.3 Anxiolytics and Sedative-Hypnotics

Get a general idea about anxiety and insomnia. Get a general idea about GABA and its functions and neurochemistry, and the distribution, structures and functions of GABA receptor. Get a general idea about Melatonin and its functions and neurochemistry, and the distribution, structures and functions of Melatonin receptor.

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.

Including the following specific drugs:

 Agents that cause CNS depression via agonism of GABA_A receptors: Barbiturates; Benzodiazepines (e.g. Chlodiazepoxide, Diazepam); Nonbenzodiazepines (e.g. Zolpidem, esZopiclone, Zaleplon)

 Agents that modulate melatonin circadian systems: Ramelteon, Tasimelteon.

 3.3.1 Anti-seizure drug targets

3.3.2 Anti-seizure drugs:

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. Including the following specific drugs:

The old ureide drugs like: bartiturates, hydantions and Benzodiazepines

The more recent drugs including: Iminostilbenes, biscarbamates (approved in 1990s) and its metabolism caused toxicity;

Amnio acid analogs (approved in the 2000s): gabapentin and the more important Lyrica; Sabril for infant seizure.

Levetiracetam (FDA approved in 2008); Lamotrigine (

3.3.3 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  

3.4. 教学评价

Quick summary test and discuss selected frequently asked questions.

Section 4 Drugs affecting the cardiovascular system

4.1.教学目标

Learn the drugs used to treat hyperlipoproteinemics, thrombotic conditions, hypertension, congestive heart failure, ischemic heart disease, and cardiac arrhythmia.

Get a general idea of how generations of drugs improve the efficacy/safety of treatments for these chronic diseases.

Have a concept about the complexity and importance of combination treatment for chronic cardiovascular diseases.

4.2.教学重难点

The pharmacophore structure of statins is related to their mechanism of action.

Aspirin has a special mechanism of action that makes it the only COX inhibitor with antiplatelet properties.

Purinergic receptor antagonists are prodrugs that irreversibly inactivates the target. The later generations improve safety and reduce drug interactions.

Warfarin's mechanism of action is related to its structure, special features and safety considerations.

Improvements of generations of heparin drugs are based on its binding motif to the target and off-target sites.

SAR studies of thiazides.

Rational design and the progressive development of ACEIs.

Selectivity of β- blockers and its relationship to reduced side effects.

Structures of 1,4-DHP are related to individual drug's specific properties.

The steroid nucleus of cardiac glycosides must adopt the U shape.

Special features of organic nitrates.

4.3.教学内容

4.3.1 Drugs used to treat hyperlipoproteinemics: Statins; Bile acid sequestrants; Fibrates; Others: niacin, ezetimibe, etc.

4.3.2 Drugs used to treat thrombotic conditions

Antiplatelets: COX-1 inhibitors; Platelet P2Y purinergic receptor / ADP receptor antagonists; Phosphodiesterase inhibitors; Glycoprotein IIb/IIIa receptor antagonists; Protease-activated receptor-1 (PAR-1) antagonists.

Anticoagulants: Oral anticoagulants; Heparin-based anticoagulants; Direct thrombin inhibitors; Direct factor Xa inhibitors; Thrombolytics

4.3.3 Drugs used to treat hypertension

Diuretics: Carbonic anhydrase inhibitors; Loop (high-ceiling) diuretics; Thiazides; K+-sparing diuretics

Renin-angiotensin pathway blockers: ACE inhibitors; Renin inhibitors; Angiotensin receptor antagonists

Calcium blockers: 1,4-dihydropyridines; Phenylalkylamines; Benzothiazepines; Sympatholytics; Peripherally acting: β- blockers; Centrally acting: methyldopa, α2-adrenergic agonists / I1 agonists

Adrenergic neuron blocking agents and ganglionic blockers

Vasodilators: Hydralazine hydrochloride; Potassium channel openers; Nitrodilators; Phosphodiesterase inhibitors

4.3.4 Drugs used to treat congestive heart failure

First-line: ACEIs/ARBs, β-blockers, MR antagonists.

Second-line: cardiac glycosides, PDE3Is, β-agonists.

Newer drugs

4.3.5 Drugs used to treat ischemic heart disease

organic nitrates; calcium channel blockers; β-blockers (propranolol, metoprolol, carvedilol)

4.3.6 Drugs used to treat cardiac arrhythmia

sodium channel blockers; β-adrenergic receptor blockers; potassium channel blockers; calcium channel blockers

4.教学方法

Based on the introduction of case study, improve the student understanding factors including physicochemical and physiological characteristics that influence drug performance in vivo and in vitro

5.教学评价

Quick summary test and discuss selected frequently asked questions.

Section 5. Drugs affecting the hormonal systems

5.1.教学目标

Learn the drugs used to diabetes and osteoporosis.

Get a general idea of how biological (protein) drugs have very different considerations compared to small molecule drugs.

5.2.教学重难点

The development of meal-time and long-acting insulin is based on the aggregation states of human insulin.

The advantage of GLP-1 analogs over insulin, and their highly competitive history of development.

DPP-4 inhibitors can have very different pharmacophores.

Metformin's structure is related to its major side effect.

How the second generation of sulfonylureas greatly reduced the side effects.

Bisphosphonates' pharmacophore is directly related to their unique PK properties and mechanism of action, while individual drugs structure leads to less dosing frequency and improved side effects.  

5.3.教学内容

(1) Drugs used to treat diabetes

Insulin

GLP-1 analogs

Oral hyperglycemic agents, including: Biguanides; Insulin secretagogues; Insulin sensitizers; α-glucosidase inhibitors; DPP-IV inhibitors; Amylin antagonists; SGLT2 inhibitors

(2) Drugs used to treat osteoporosis

Anti-resorptive agents: Estrogen analogs; Selective estrogen receptor modulators; Bisphosphonates; and Calcitonin

Bone-forming agents: Forteo and Inorganic salts

4.教学方法

Firstly, ask student could combine theory and knowledge frame between pharmaceutics and biopharmaceutics & pharmacokinetics, through typical case introduction. Secondly, enhance the understanding of new drug development process, thereafter to construct the pharmaceutical knowledge system.

5.教学评价

Quick summary test and discuss selected frequently asked questions.

Section 6. Drugs affecting the immune system

1.教学目标

Learn the most commonly used anti-inflammatory drugs.

Have a general concept about the applicable indications for each class of anti-inflammatory drug, as well as their side effects, especially over long-term use.

2.教学重难点

SAR studies for glucocorticoids lead to development of generations of systemic drugs with improved selectivity and reduced side effects (to some degree).

Topical, inhaled and intranasal glucocorticoids require very different PK properties. These were achieved with both structural modification and formulation change.

Toxicity of acetaminophen is related to its metabolism.

Major side effect of NSAID is the GI toxicity. Some are designed as prodrugs to reduce this side effect.

selective NSAID has significantly reduced GI toxicity.

First generation of H1 antihistamines are more often used as sleep aids or for motion sickness rather than anti-inflammatory drugs, due to their pronounced side effects.

Second generation H1 antihistamines are commonly used allergy medications, with significantly reduced crossing of the blood-brain barrier.

H2 antihistamines are used as treatment for duodenal and gastric ulcers, and OTC for acid indigestion. This is due to the diverse activities of histamine.

3.教学内容

(1) Adrenocorticoids

Systemic；Topical；Inhaled and intranasal

(2) Nonsteroidal anti-inflammatory drugs：Acetaminophen

non-selective NSAID：Salicylates；Arylalkanoic acids；N-arylanthranilic acids；Oxicams and selective NSAID

(3) Antihistamines

H1 antihistamines: including the first generation： Ethylenediamines； Ethanolamine ethers；Alkyl amines；Piperizines； Tricyclic; and the Second generation：H2 antihistamines

4.教学方法

Teaching theory and case presentation.

5.教学评价

Quick summary test and discuss selected frequently asked questions.

Section 7. Chemotherapeutic agents

1.教学目标

7.1.1 This section covers mainly cancer chemotherapeutic drugs and infectious disease treatment pharmaceuticals. Students should master the first-line drugs used in clinic, including the drug structure, mechanism of action, metabolism of selected drugs, as well as the synthetic method for selected drugs.

7.1.2 Have update knowledge of the novel drug, the most pursued drug targets in each research area, especially cancer drugs and drugs used in the infectious disease area.

2.教学重难点

Drugs developed in the past ten to five years, these newly reported drugs work through novel target and pathway, as represented by the fast pace development in the research area of cancer and anti-viral drugs.  

3.教学内容

 As listed above, this section covers the following contents: 1. Cancer chemotherapy; 2. Antibiotic; 3. Anti-viral pharmaceuticals; 4. Antifungal agents; 5 anti-mycobacterial agents. Again, for each chapter, the drug target, pharmacophore, mechanism of action and metabolism are the major teaching contents.

4.教学方法

A combination of in class PPT, recommended reading assignment and discussion.

5.教学评价

How well the students are involved in the class, feedback from student comments, quality of the teaching PPTs.

四、学时分配

表2：各章节的具体内容和学时分配表

五、教学进度

表3：教学进度表

六、教材及参考书目

 1. Foye’s Principles of Medicinal Chemistry, 7th edition

 2.尤启冬主编，《药物化学》，化学工业出版社，2017，第三版

七、Teaching method

 1. Teaching method: Teaching the basic concepts and principles of this course in class using PPT and video, etc.

 2. Homework assignment after each lecture.

 3. Discussion and self-taught. The heuristic teaching method will be employed in the class, and flipping classroom will be used 1-2 times to encourage student to actively involved in the learning process.

八、考核方式及评定方法

（一）课程考核与课程目标的对应关系

表4：课程考核与课程目标的对应关系表

（二）评定方法

评定方法

平时成绩：10%，两次过程化考核考试：各占30%，期末考试40%.

（三）评分标准