Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals

J Med Chem. 2014 Dec 26;57(24):10257-74. doi: 10.1021/jm501100b. Epub 2014 Oct 7.


Nitrogen heterocycles are among the most significant structural components of pharmaceuticals. Analysis of our database of U.S. FDA approved drugs reveals that 59% of unique small-molecule drugs contain a nitrogen heterocycle. In this review we report on the top 25 most commonly utilized nitrogen heterocycles found in pharmaceuticals. The main part of our analysis is divided into seven sections: (1) three- and four-membered heterocycles, (2) five-, (3) six-, and (4) seven- and eight-membered heterocycles, as well as (5) fused, (6) bridged bicyclic, and (7) macrocyclic nitrogen heterocycles. Each section reveals the top nitrogen heterocyclic structures and their relative impact for that ring type. For the most commonly used nitrogen heterocycles, we report detailed substitution patterns, highlight common architectural cores, and discuss unusual or rare structures.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Catalysis
  • Heterocyclic Compounds / chemistry*
  • Nitrogen / chemistry*
  • Pharmaceutical Preparations / analysis*
  • United States
  • United States Food and Drug Administration


  • Heterocyclic Compounds
  • Pharmaceutical Preparations
  • Nitrogen