Chem
453:
Bioorganic
Chemistry
Spring
2011
–
Modern
Medicinal
Chemistry
Overview - The focus of this semester is an overview of the drug discovery process
(target selection/validation, lead discovery including combinatorial chemistry and HTS,
lead optimization/CADD, FDA processing, clinical trials, etc.). The chemistry that will be
emphasized is the difference between process/development (green chemistry) and lead
discovery. Topics will focus on classes of drugs currently in clinical use, or on the
horizon (HMGCoA reductase inhibitors (Lipitor, etc.), angiotensin-converting-enzyme
(ACE) inhibitors, tyrosine-kinase inhibitors (Gleevac, etc.), HIV protease inhibitors,
superoxide dismutase mimetics, biologics, antibodies, etc.). Students will be responsible
for presenting to the class the synthetic routes developed both for the discovery and for
the commercialization of these drugs.
Modern
Medicinal
Chemistry,
Professor
Garland
R.
Marshall
Lecture: Tu Th: 8:30-10:00 (L311??) Office hrs: By appointment as many as
needed. Office: Lab Sciences, Room 201. Phone: 935-7911 Email:
garlandm@gmail.com
Supplementary Texts.
Lednicer and Mitscher, The Organic Chemistry of Drug Synthesis, Vol 1 & 2, Wiley, 1980
(Prof. Marshall has a copy).
Annual Reports in Medicinal Chemistry, Division of Medicinal Chemistry, ACS, Academic
Press (vol. 45 is latest, Prof. Marshall has a copies).
Grading: There will be one take-home 1-hour exam, a student presentation, and one 2hour final exam. The final will be worth 200 points, the 1-hr exam 100 points, and the
student presentation worth 100 points.
Required Prerequisite Course: Chem 262, or permission of the instructor.
Syllabus: Brief summary of topics covered in lectures.
1. Jan. 18 –Introduction to Drug Discovery - GRM
2. Jan. 20 – Target Selection/Validation - GRM
3. Jan. 25 – Molecular Modeling (Prof. Jay Ponder)
4. Jan. 27 - Structure-Based Design - GRM
5. Feb. 1 – Combinatorial Chemistry - GRM
6. Feb. 3 – High-throughput Screening - GRM
7. Feb. 10 – Discovery vs. Development Chemistry - GRM
8. Feb. 15 – Hypertension – ACE Inhibitors - GRM
9. Feb. 17 – Chemistry of ACE Inhibition (student) - GRM
10. Feb. 22 – Oncology I – Tyrosine-Kinase Inhibitors (Prof. Jim Janetka)
11. Feb. 24 – Chemistry of Tyrosine-Kinase Inhibitors (student) (Prof. Jim Janetka)
12. Mar. 1 – Inflammation – Superoxide dismutase mimetics (Dr. Dennis Riley)
13. Mar. 3 - Chemistry of SOD mimetics (student) (Dr. Dennis Riley)
14. Mar. 8 - GMP/Toxicity/Clinical Trials - (Dr. Dennis Riley)
15. Mar. 10 – High Cholesterol - HMGCoA Inhibitors
Spring Break – March 14-20
16. Mar.22 – Chemistry of HMGCoA Inhibitors (student)
17. Mar. 24 – Antivirals – HIV-protease Inhibitors
18. Mar. 29 - Chemistry of HIV-protease Inhibitors (student)
19. Mar. 31 – Oncology II - Topoisomerase inhibitors 20.
20. Apr. 5 - Chemistry of Topoisomerase Inhibitors (student)
21. Apr. 7 - Oncology III – Inhibitors of Actin Polymerization – GRM
21. Apr.12 – Antimicrobials I – Bacterial Cell-wall Inhibitors
22. Apr. 14 - Chemistry of Cell-wall Inhibitors (student)
23. Apr. 21– Antimicrobials II – Targeting the ribosome
24. Apr. 26 - Chemistry of Protein-synthesis Inhibitors (student)
25. Apr. 28 – Antimicrobials III – Targeting Virulence
27. May 3 – Antivirals II – Nucleotide Analogs
28. May 5 - Chemistry of Nucleotide Antivirals (student)
29. May 9 – Antivirals III – Non-nucleoside Inhibitors
31. May 10 – Take-home Final Exam
Course
Handouts:
Chem 453 - Spring 2011 Course Notes Manual (In preparation)