ToolBook and Chem3D Tutorials

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Index

• Directions for Viewing ToolBook Tutorials
• Basic Concepts in Medicinal Chemistry:  A Series of Tutorials for Instruction and Review
• Medicinal Chemistry Tutorials: Designed for the Biomedical Sciences and Therapeutics modules (PHBMS 423-427)
• Tutorials for PHBMS 422 (Neuro/Psych Module)
• Tutorials for PHBMS 423 (GI/Rheum/Inflam Module)
• Tutorials for PHBMS 424 (Cardiovascular Module)
• Tutorials for PHBMS 425 (Endocrine Module)
• Tutorials for PHBMS 426 (Infectious Disease Module)
• Tutorials for PHBMS 427 (Pulmonary/Oncology Module)
• Directions for Viewing Chem3D Structures
• Chem3D Structures and Tutorials
• Author Information

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PLEASE READ:  Directions for Downloading and Installing the Plugin Required to View ToolBook Tutorials

In order to view the tutorials, it is necessary that the plugin, Neuron, version 7.1x be properly installed on your computer.  This plugin works with both Netscape Navigator/Communicator and Microsoft Internet Explorer and allows you to run ToolBook files without purchasing or installing other ToolBook software.  Neuron is available free of charge from Click 2 Learn (formerly Asymetrix) and can be directly downloaded from this page.

Download Neuron 7.1x here

Remember where you saved the file.  Once the download is finished, go to the folder that contains neuron.exe.  Double click the file icon to install Neuron 7.1x.  A program folder will automatically be created for you.

Once the plugin is installed, it must be set in Non-secure Mode in order for the tutorials to load correctly.  This mode allows all functions of the ToolBook tutorials to to load correctly and run correctly. This mode allows all functions of the ToolBook tutorials to run.  The "Secure mode" has only limited functionality and WILL NOT work with these tutorials.  If you like, you can also use "Secure Mode-Confirm".  This will ask you to choose between Secure and Non-Secure Mode EVERYTIME you load a tutorial.  The author finds this annoying; however, it is an option if you wish to use it.

To set the plugin in Non-secure mode, select "Start" (bottom left-hand corner of screen) followed by "Programs", "Asymetrix Learning Systems", "ToolBook II Neuron 7", and "Non-secure Mode" (or "Secure Mode-Confirm").

If you have problems the plugin, please contact me and I will assist you (contact information is at the bottom of this page)

Index

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Basic Concepts Tutorials

• Basic Concepts in Medicinal Chemistry
  This will link you to a series of tutorials which review the basic medicinal chemistry concepts that govern drug action.  They should be used as needed to review concepts which may have been forgotten.

Index

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Medicinal Chemistry Tutorials for Specific Drug Classes and PHBMS Modules
For each of the drug classes listed below, questions have been developed to explore (when appropriate) receptor binding, mechanism of action, metabolism, SAR, toxicity, and background information on the disease state.  Questions have been written from a medicinal chemistry perspective (as you might imagine!).

Tutorials for PHBMS 422 (Neuro/Psych Module):

• Non-Steroidal Antiinflammatory Drugs (NSAIDs) and related agents
  Includes salicylates, fenamates, 3,5-pyrazolidinediones, arylacetic acids, acetaminophen, and some DMARDs.
  
• Opioids
  Includes discussions of morphine, morphine analogs, partial and full antagonists as well as other opioid subclassifications.

Tutorials for PHBMS 423 (GI/Rheum/Inflam Module):

• Prostaglandins and Leukotrienes
  Includes nomenclature, biosynthesis, metabolism, therapeutic uses, and inhibitors

• Agents for the Treatment of Gout
  Includes questions regarding uric acid, colchicine, uricosuric agents, and allopurinol.

• Histamine, Antihistamines, and Agents for Peptic Ulcer Disorder
  Includes histamine, the various chemical classes of H-1 antagonists, H-2 antagonists, proton pump inhibitors, and alpha glucosidase inhibitors.

Tutorials for PHBMS 424 (Cardiovascular Module):

• Antihyperlipidemic Agents
  Includes endogenous and exogenous pathways of cholesterol transport, HMG-CoA reductase inhibitors, bile acid sequestrants, and fibrates.

• Antianginal Agents
  Includes organic nitrates, calcium channel blockers, and a few miscellaneous agents

• Cardiac Glycosides
  Primarily discusses the differences between digoxin, digitoxin, and the lanatosides.  Additional positive inotropic agents are briefly discussed.

• Diuretics
  Includes osmotic diuretics, carbonic anhydrase inhibitors, thiazides, loop diuretics, and potassium-sparing diuretics.
  
• Inhibitors of the Renin-Angiotensin Pathway
  Includes angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists.
  
• Anticoagulants, Antithrombotics, and Related Agents
  Includes questions for the coagulation cascade, oral and parenteral anticoagulants, antithrombotic agents, thrombolytic agents and those agents used to reverse the actions of these compounds.

Tutorials for PHBMS 425 (Endocrine Module):

• Steroid Nomenclature, Identification, and SAR
  This tutorial currently contains two chapters:  (1) a review of steroid numbering, ring junctures, and nomenclature, and (2) a stepwise process by which to identify endogenous steroids and the aglycone portion of a cardiac glycosides.  Future chapters will include SAR for oral bioavailability, parenteral use, separation of anabolic and androgenic effects, and separation of glucocorticoid and mineralocorticoid activity.

• Adrenocortical Steroids
  This tutorial examines ACTH, the SAR for glucocorticoids and mineralocorticoids, iatrogenic adrenal insufficiency, inhibitors of steroid biosynthesis, and a cursory overview of identifying steroids.

Tutorials for PHBMS 426 (Infectious Disease Module):

• Answers to the Study Guide Questions
  This contains the questions and answers to the study guide distributed with the notes for PHBMS 426.  It does not include all classes of antibiotics but does contain questions and explanations for sulfonamides, beta-lactams, aminoglycosides, and tetracyclines.

• Antitubercular Agents
  This tutorial contains summary reviews of first-line agents for the treatment of tuberculosis.  This includes isoniazid, ethambutol, rifampin, and pyrazinamide.  Also included is a five question quiz regarding these agents.  Students in the authors course are responsible for reviewing this tutorial prior to the examination which includes these agents.
  
• Antiviral Agents
  This tutorial contains three sections:  (1) a review of the viral replication cycle as well as the basic concepts of DNA and RNA replication and transcription; (2) overviews of specific compounds and classes of compounds; and (3) review questions pertaining to both lecture material as well as the first two sections of the tutorial.

Tutorials for PHBMS 427 (Pulmonary/Oncology Module)

• Introduction to Antineoplastic Agents and Alkylating Agents
  This tutorial reviews the nomenclature for antimetabolites as well as the mechanism of action and some SAR of alkylating agents.
  
• Summary Sheets for Antineoplastic Agents
  This tutorial contains summations of the mechanisms of action and mechanisms of resistance for alkylating agents, antimetabolites, and intercalating agents.

Index

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Directions for Viewing Chem3D Structures
Regardless of whether you are viewing the Chem 3D structures online or from a CD-ROM, you will need to install the Chem3D Plugin. 

The plugin is free and can be downloaded from this site.  Save the downloaded file to your computer. It is recommended that you save this to your desktop so that you can easily locate it. The file is named “chem3Dviewer.exe”. Simply run the executable file to install the plugin. The directions are easy to follow.

Download Chem3D Plugin here.

Index

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Chem3D Structures and Tutorials

Tutorials for Biomedical Science and Therapeutics Courses

• Introduction
  Please take the time to go through the instructional tutorial prior to viewing the other models.  It will describe the features of Chem 3D models and how to make changes.
  
• The Binding of NSAIDs to their Receptor
  This exercise is for use with PHBMS 423 and examines the active, binding conformations of indomethacin and diclofenac as representitives of the NSAID class of agents.
  
• The Role of Aromatic Substitution on 1,4-Dihydropyridine (DHP) Binding
  This exercise is for use with PHBMS 424.  It examines the active conformation of 1,4-DHP binding and the roles of aromatic and ester substitutions. 
  
• Thyroid SAR
  This exercise is for use with PHBMS 425.  It examines the active conformation of T3 and T4, the role of the 3- and 5-Iodo atoms in "locking in" this active conformation, and the relative binding and potency of T3 and T4. 

Structures used in lectures

• Alpha and Beta Steroids
  
• Major and Minor Grooves of DNA

• Structural Comparison of the D-Ala-D-Ala Portion of the Bacterial Cell Wall with b-Lactam Antibiotics

• Comparison of CMP to Ara-CMP
  
• Affinity Labels
  
• The R- and S- Isomers of Norepinephrine

Index

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Author Information

Marc W. Harrold, Ph.D.
Professor of Medicinal Chemistry
Duquesne University
School of Pharmacy
Pittsburgh, PA 15282
harrold@duq.edu
(412) 396-6364

Acknowledgements

The author would like to thank Stacy Eisler and Melissa Flores for their assistance in editing and reviewing portions of the above tutorials.

The URL for this page is: http://www.home.duq.edu/~harrold/index.html
Copyright © 2001 Duquesne University
Revised: 9/17/2007

Index