An Update on the Nitrogen Heterocycle Compositions and Properties of U.S. FDA-Approved Pharmaceuticals (2013–2023)

This Perspective is a continuation of our analysis of
U.S. FDA-approved
small-molecule drugs (1938–2012) containing nitrogen heterocycles.
In this study we report drug structure and property analyses of 321
unique new small-molecule drugs approved from January 2013 to December
2023 as well as information about frequency of important heteroatoms
such as sulfur and fluorine and key small nitrogen substituents (CN
and NO2). The most notable change is an incredible increase
in drugs containing at least one nitrogen heterocycle82%,
compared to 59% from preceding decadesas well as a significant
increase in the number of nitrogen heterocycles per drug. Pyridine
has claimed the #1 high-frequency nitrogen heterocycle occurrence
spot from piperidine (#2), with pyrimidine (#5), pyrazole (#6), and
morpholine (#9) being the big top 10 climbers. Also notable is high
number of fused nitrogen heterocycles, apparently driven largely by
newly approved cancer drugs.