Chemistry Reference
In-Depth Information
Clinical Trials. The isosteric substitution of the tiourea by an N-cianoguanidine
led the synthesis of cimetidine (Fig.
18
), the first anti gastric ulcer drug to hit the
market, keeping the activity and bioavailability of methiamide without its severe
toxic effects [40, 49].
Figure 18:
Chemical structures of Burimamide, Methiamide and Cimetidine.
CONCLUSION
The bioisosteric replacement strategy can be very useful in many ways during
drug properties optimization, including the design of penicillins that can be taken
orally, the design of novel calcium channel antagonists with increased half-life
and the synthesis of antidepressants with simplified industrial preparation. Such
chemical optimizations are driven by the knowledge created over many years of
Medicinal Chemists experience during the design of several drugs in the modern
era. However, there is a need for rationalizing this task and identifying useful
bioisosteric replacements faster, reducing time and costs. In this scenario, we can
verify that many scientific groups are using chemical databases and molecular
descriptors knowledge trying to achieve the development of reliable
chemoinformatic approaches able to identify structural similarities among groups
of molecular fragments. This will make bioisosteric replacements an easier task
and help chemists to make effective structural modifications quickly during the
different drug design steps.
