ACS Publications Division

Modern Drug Discovery


Modern Drug Discovery Home Page


Table of Contents

November-December 1998
Volume 1, Number 2


20 Nitric oxide-releasing compounds: From basic research to promising drugs
By attaching NO-releasing functional groups to carrier molecules, new biomedical research tools and potential clinical agents that spontaneously generate bioactive nitric oxide have been made possible.
Larry K. Keefer
31 From hypertension to angina to Viagra
Jim Kling
On its way to becoming Viagra, UK-92,480 changed from a drug for hypertension to a drug for angina, and then changed again when a 10-day toleration study in Wales turned up an unusual side effect.
41 Rational drug design: Controlling the size of the haystack
Donald B. Boyd
Combinatorial chemistry creates larger and larger haystacks in which to find the needle. Rational design attempts to focus the design process on the smallest possible set of viable compounds.
49 Illuminating the SNP genomic code
Anthony W. Czarnik
Most DNA sequence differences between any two humans are single base pair differences, or single nucleotide polymorphisms (SNPs). A fiber-optics-based technology for SNP detection is a new tool for discovery of genes influencing complex traits and new drug development targets.


7 Editorial
9 Letters
11 In Brief
  • This year's flu
  • A connection between secretin and autism?
  • Relief for sufferers of rheumatoid arthritis
  • Surfers beware
14 Analysis
The human genome: A race to the finish?
57 Reviews
  • Her-2: The Making of Herceptin, a Revolutionary Treatment for Breast Cancer
  • The Excruciating History of Dentistry: Toothsome Tales & Oral Oddities from Babylon to Braces
59 New Products
62 Meetings
63 Ad Index
64 EtCetera


cGMP, Zaprinast, and Viagra (sildenafil) illustrate the molecular evolution described in our story on Viagra. Viagra, an inhibitor of phoshodiesterase 5 (PDE 5), was discovered by using a rational drug design approach. As explained in Jim Kling's article, Pfizer chemists began their quest for a PDE inhibitor by comparing structures of cGMP (top), a substrate of some PDEs, a Zaprinast (middle), which was one of the few know PDE inhibitors in 1986. Structural comparisons suggested a line of experimentation that eventually led to Viagra (bottom). Cover illustration by gh multimedia.