CHEM 4347
Advanced Interdisciplinary Topics
Drug Design
9:55 – 11:10 TTh

Instructors: Dr. Steven Bachrach
215D MEB
Office Hours: MWF 1:00-2:00pm
or by appointment
Dr. Adam Urbach
215B MEB
Office Hours: MWF 12:00-1:00pm
or by appointment

Textbook: Biochemistry, Mathews, Van Holde, Ahern, 3rd Edition

Course Description:

This senior-level course will present the major concepts involved in modern drug design, primarily through case study. A major feature of the class will be how multiple chemical disciplines – biochemistry, organic synthesis, physical chemistry, computational chemistry, chemometrics – combine to solve drug design problems.

Topics and Schedule:

The following is a list of topics and the tentative weeks that these topics will be discussed in class.

Week 1: Introduction to Drug Design Principles, ADME/Tox

Week 2-3: Introduction to Protein Structure, Function, Thermodynamics and Kinetics

Week 4-5: Introduction to QSAR, Docking and Crystallography

Weeks 6-16: Case studies of various drug developments. We will discuss a number of different drugs and different diseases targeted by researchers. This core portion of the class will involve extensive reading of the primary chemistry, biochemistry, and biology literature. Students will be asked to prepare to lead and participate in class discussions. This portion of the class will be much more like a seminar than a lecture class.

Web Site:


Your grade will be determined in the following manner:

Mid-Term Exam 100 points
Final term Paper 100 points
Class Participation 200 points
Total 400 points

The Mid-Term Exam will be held following the QSAR/docking/crystallogrpahy section, approximately during the 6th week of class. This will be a written exam and is worth one-quarter of the overall grade. A term paper will be due on the last day of class. Further information on the length, scope, and topics of this paper will be presented about midway through the semester. This paper will be worth one-quarter of the overall grade.

The remainder of your grade will be based on your class participation. Students are expected to come to class prepared to discuss the pertinent topics of the day. During the last portion of the semester we will discuss case studies of various pharmaceuticals, their design strategies, their syntheses, and their successes and failures. Each student will act as discussion leader for two classes. The discussion leader will be expected to come to class ready to describe the relevant literature, to promote and guide the class discussion, and to ask questions and make comments. For the first pass through the group of student discussion leaders, you will be assigned a major paper from the chemical literature, but will likely have to read additional references to properly place the major paper in its proper context. For the second pass through the group, each student will select their own paper, with approval of either professor. Students who are not leading the discussion are expected to be prepared to participate in the discussions. Your level of participation, your ability as discussion leader, and the insight you display will be evaluated and will comprise one-half of your course grade.

Drug Design Resources

Multiple Regression Software - this zipped file contains four files: Nonlin.exe, Nonlin.doc,, and HeatForm.NLR. The first file (Nonlin.exe) is the actually program that performs the regression analysis. The Nonlin.doc file is a MS Word file that describes the use of the program in detail. The file is a very short description of getting started with the program. The last file (HeatForm.NLR) is the data file that you will analize. It contains the heats of formation for a number of alkanes, along with the number of carbon and hydrogen atoms.

Articles about drug costs

Pharmaceuticals review - Chemical and Engineering News, Dec. 5, 2005


Student-led Discussion Schedule

Date Student Paper
March 2 Sarah Discovery of Imidazo[1,2-b][1,2,4]triazines as GABAA 2/3 Subtype Selective Agonists for the Treatment of Anxiety J. Med. Chem., 2006, 49, 1235.
Cara Anilinoquinazoline Inhibitors of Fructose 1,6-Bisphosphatase Bind at a Novel Allosteric Site: Synthesis, In Vitro Characterization, and X-ray Crystallography J. Med. Chem., 2002, 45, 3865.
March 7 Katerine L-735,524: The Design of a Potent and Orally Bioavailable HIV Protease Inhibitor J. Med. Chem., 1994, 37, 3443.
Thomas Viracept (Nelfinavir Mesylate, AG1343): A Potent, Orally Bioavailable Inhibitor of HIV-1 Protease J. Med. Chem., 1997, 40, 3979.
March 9 Ollie Discovery of 1-[3-(Aminomethyl)phenyl]-N-[3-fluoro-2'-(methylsulfonyl)- [1,1'-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide (DPC423), a Highly Potent, Selective, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa1 J. Med. Chem., 2001, 44, 566.
Claire Structure-Based Design of Cathepsin K Inhibitors Containing a Benzyloxy-Substituted Benzoyl Peptidomimetic J. Med. Chem., 1998, 41, 3923.
March 21 Emily The discovery of rofecoxib, [MK 966, Vioxx, 4-(4'-methylsulfonylphenyl)-3-phenyl-2(5H)-furanone], an orally active cyclooxygenase-2 inhibitor. Bioorganic & Medicinal Chemistry Letters, 1999, 9, 1773.
Catherine Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature, 1996, 384, 644.
March 30 Cara Synthesis and Serotonergic Activity of 3-[2-(Pyrrolidin-1-yl)ethyl]indoles: Potent Agonists for the h5-HT1D Receptor with High Selectivity over the h5-HT1B Receptor J. Med. Chem., 1999, 42, 677-690.
April 4 Ollie Synthesis and In Vitro Studies of Novel Pyrimidinyl Peptidomimetics as Potential Antimalarial Therapeutic Agents J. Med. Chem., 2002, 45, 3491 - 3496.
April 6 Katerine Estradiol-16-carboxylic Acid Esters as Locally Active Estrogens J. Med. Chem., 2001, 44, 1802-1814.
April 11 Claire 3-Benzisothiazolylpiperazine Derivatives as Potential Atypical Antipsychotic Agents J. Med. Chem., 1996, 39, 143 - 148.
April 13 Emily The Discovery of Tadalafil: A Novel and Highly Selective PDE5 Inhibitor. 2: 2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione Analogues J. Med. Chem., 2003, 46, 4533-4542.
April 18 Sarah Synthesis, Cardiotonic Activity, and Structure-Activity Relationships of 17-Guanylhydrazone Derivatives of 5-Androstane-3,14-diol Acting on the Na+,K+-ATPase Receptor J. Med. Chem., 1997, 40, 3484-3488.
April 20 Catherine Synthesis of N-Glyoxyl Prolyl and Pipecolyl Amides and Thioesters and Evaluation of Their In Vitro and In Vivo Nerve Regenerative Effects J. Med. Chem., 2002, 45, 3549-3557.
April 25 Thomas Structure-Activity Studies on Anticonvulsant Sugar Sulfamates Related to Topiramate. Enhanced Potency with Cyclic Sulfate Derivatives J. Med. Chem., 1998, 41, 1315-1343.