Organic Chemistry and Drug Development:
Synthesis and Analysis of a Library of Hydrazones
Reading Assignment: Review Loudon, G.M.
ed.; Oxford University Press:
New York, 2002, pgs 874-876.
You are nearing the end of your year in organic chemistry. By now you have learned countless
organic reactions and have a basic understanding of mechanism and synthesis. Organic chemists apply
this knowledge every day to design and synthesize molecules that are useful as catalysts, polymers,
and medicines. In the area of drug discovery the initial focus is on the discovery of “hits” which are
compounds that exhibit potency for a selected target such as an enzyme, receptor, DNA, or RNA.
discovery of hits usually involves screening a large collection of compounds, often referred to as a
library of compounds, obtained from natural products or synthesized chemically. Some libraries
contain greater than a million compounds
and a great diversity of structures are represented. Once a
hit is identified medicinal chemists synthesize derivatives to attempt to optimize the potency,
selectivity, pharmacokinetic and physiochemical properties and to minimize toxicity
activity relationships (SAR) data is collected which attempts to make a correlation between the
structure of a molecule and its biological activity
. This information is often coupled with NMR and x-
ray crystal data, which supports structure based design.
The entire drug discovery process takes 12-15
years, approximately $1 billion and involves a team of scientists from the many areas including
medicinal, analytical, and process chemistry, molecular biology, toxicology, pharmacology, cell
biology, and biochemistry
Combinatorial chemistry has given the chemists the ability to produce large libraries of compounds for
biological testing. This method involves synthesizing and testing
Identification of an active compound can be done using fewer reactions and biological tests than
synthesizing each molecule individually and therefore can save time and money. Combinatorial
synthesis has led to the discovery of some current drugs including indivir, an FDA-approved HIV