Beyond C, H, O, and N! Analysis of the elemental composition of U.S. FDA approved drug architectures

• Published in: Journal of medicinal chemistry Vol. 57; no. 23; pp. 9764 - 9773
• Main Authors: Smith, Brandon R, Eastman, Candice M, Njardarson, Jon T
• Format: Journal Article
• Language: English
• Published: United States 11.12.2014
• Subjects: Chlorine - chemistry; Drug Approval; Fluorine - chemistry; Pharmaceutical Preparations - analysis; Phosphorus - chemistry; Sulfur - chemistry; United States; United States Food and Drug Administration; United States
• ISSN: 1520-4804
• DOI: 10.1021/jm501105n

The diversity of elements among U.S. Food and Drug Administration (FDA) approved pharmaceuticals is analyzed and reported, with a focus on atoms other than carbon, hydrogen, oxygen, and nitrogen. Our analysis reveals that sulfur, chlorine, fluorine, and phosphorous represent about 90% of elemental substitutions, with sulfur being the fifth most used element followed closely by chlorine, then fluorine and finally phosphorous in the eighth place. The remaining 10% of substitutions are represented by 16 other elements of which bromine, iodine, and iron occur most frequently. The most detailed parts of our analysis are focused on chlorinated drugs as a function of approval date, disease condition, chlorine attachment, and structure. To better aid our chlorine drug analyses, a new poster showcasing the structures of chlorinated pharmaceuticals was created specifically for this study. Phosphorus, bromine, and iodine containing drugs are analyzed closely as well, followed by a discussion about other elements.