The Properties of Known Drugs. 1. Molecular Frameworks

TLDR

Drug molecules can be organized by grouping atoms into ring, linker, framework, and side chain categories. The study aims to identify common drug shapes using shape description methods and to discuss how these findings can guide future drug discovery. Researchers analyzed 5,120 drugs with two shape‑description approaches—one based on 2D structures ignoring atom types, and a second incorporating atom type, hybridization, and bond order—to enumerate molecular frameworks. The analysis revealed 1,179 distinct frameworks (2D) among 5,120 drugs, with the 32 most common covering half the set, indicating low shape diversity; when atom details were included, 2,506 frameworks were identified and the 42 most frequent accounted for only a quarter of the drugs.

Abstract

In order to better understand the common features present in drug molecules, we use shape description methods to analyze a database of commercially available drugs and prepare a list of common drug shapes. A useful way of organizing this structural data is to group the atoms of each drug molecule into ring, linker, framework, and side chain atoms. On the basis of the two-dimensional molecular structures (without regard to atom type, hybridization, and bond order), there are 1179 different frameworks among the 5120 compounds analyzed. However, the shapes of half of the drugs in the database are described by the 32 most frequently occurring frameworks. This suggests that the diversity of shapes in the set of known drugs is extremely low. In our second method of analysis, in which atom type, hybridization, and bond order are considered, more diversity is seen; there are 2506 different frameworks among the 5120 compounds in the database, and the most frequently occurring 42 frameworks account for only one-fourth of the drugs. We discuss the possible interpretations of these findings and the way they may be used to guide future drug discovery research.