P. 20-21 /

Myths, legends and the demise of small molecule APIs


Member of Chimica Oggi/Chemistry Today Scientific Advisory Board
Chiral Quest., Trinity House, Cambridge Business Park, Cowley Road, Cambridge, CB4 0WZ, United Kingdom

In the pharmaceutical industry there has been many fashions and trends, some might call them “bandwagons”. When I first started working in drug discovery in 1985, I was told that the day of the synthetic chemist making numerous analogues was soon to be over. Molecular modelling would be able to design new drugs without extensive chemical synthesis and “analogue bashing”. Unfortunately, the inability to accurately model water soon led to this idea being modified. Then combinatorial chemistry came along, where the industry invested many millions of dollars into a technology that made flat achiral molecules, mainly with amide bonds. Out of these endeavours came better robotics and parallel synthesis, but combinatorial chemistry did not lead directly to the discovery of many new drugs.

The use of microwaves caused quite a stir, with the famous “microwave effect”, which many now believe to be a localized thermal effect that can be reproduced by superheating in flow systems. However, microwaves are used in many drug discovery laboratories to good effect, but not readily applied to manufacture of pharmaceuticals. This leads nicely onto flow chemistry, which has seen ...