Chem 130A




This course will provide an introduction to the chemical principles behind the design and production of pharmaceutical agents.


Required Text:

Richard B. Silverman, The Organic Chemistry of Drug Design and Drug Action, 2nd Edition, Elsevier/Academic Press, 2004, ISBN 0-12-643732-7.



This class is not about memorization. It is about developing analytical thinking and problem solving skills.

Specifically, we will focus on explaining and predicting how small organic molecules bind to biological receptors, inhibit enzymes, get metabolized.

We will draw on and expand upon things covered in introductory organic chemistry such as:

• proposing reasonable arrow-pushing mechanisms for organic reactions

• predicting the reactivity of organic molecules with particular reagents


Outline (subject to change):


week 1

Intro to drug discovery: natural products, lead compounds (1, 2.1)


week 2

lead modification (2.2A-E)

pharmacophores, SAR



week 3

lead modification (2.2F-G)

Lipinski, bioavailability


Computer-aided design


week 4

receptors (3.1-3.2)

types of drug-receptor interactions, physical principles

experimental determination of drug-receptor interactions

theories of drug-receptor interactions

geometric, stereochemical, conformational, pKa concerns

structure-based design


week 5

enzyme structure and function (4.1-4.3)

what are enzymes?

standard mechanisms for catalysis, arrow-pushing



week 6

enzyme inhibition 1 (5.1-5.4B)


week 7

enzyme inhibition 2 (5.4C-5.5)


week 8

DNA/RNA issues (6)


week 9

metabolism, toxicity (7)


week 10

prodrugs, drug delivery, ion channels (8)

Miller Symposium


week 11

visit from a Sundeep Dugar, a practicing pharmaceutical chemist from industry

the big picture