What's in a Name? Drug Nomenclature and Medicinal Chemistry Trends using INN Publications.

Marta Serafini,Armando A Genazzani,Sarah Cargnin,Tracey Pirali,Alberto Massarotti,Gian Cesare Tron

doi:10.1021/acs.jmedchem.1c00181

Marta Serafini, Armando A Genazzani + Show 4 more

Open Access

https://doi.org/10.1021/acs.jmedchem.1c00181

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Abstract

The World Health Organization assigns international nonproprietary names (INN), also known as common names, to compounds upon request from drug developers. Structures of INNs are publicly available and represent a source, albeit underused, to understand trends in drug research and development. Here, we explain how a common drug name is composed and analyze chemical entities from 2000 to 2021. In the analysis, we describe some changes that intertwine chemical structure, newer therapeutic targets (e.g., kinases), including a significant increase in the use of fluorine and of heterocycles, and some other evolutionary modifications, such as the progressive increase in molecular weight. Alongside these, small signs of change can be spotted, such as the rise in spirocyclic scaffolds and small rings and the emergence of unconventional structural moieties that might forecast the future to come.

Highlights

Remember the biblical story of the Tower of Babel, in which the attempt to build a tower that would reach the heavens by the Babylonians was disrupted by the inability of the builders, that spoke different languages, to understand each other? Well, apparently there are today over 7000 spoken languages, and 34 of them are spoken by at least 45 million people.[1]
We evaluated whether medicinal chemistry has escaped from flatland in the last 20 years but found that Fsp[3] is roughly similar between period A and B (Figure 16A), in line with what was reported by Ivanenkov et al for launched drugs.[76]
This somehow is a surprising finding, and when attempting to find a trend in the last 20 years, we found a small downward trend (Figure 16B), in analogy to what reported when analyzing discovery compounds published in the Journal of Medicinal Chemistry in the period of 1995−2009.78 Despite this, small signs of change toward an enhanced spatial complexity can be observed at the granular level, and we concentrated on chirality, spirocyclic compounds, and small rings

Summary

■ INTRODUCTION

Remember the biblical story of the Tower of Babel, in which the attempt to build a tower that would reach the heavens by the Babylonians was disrupted by the inability of the builders, that spoke different languages, to understand each other? Well, apparently there are today over 7000 spoken languages, and 34 of them are spoken by at least 45 million people.[1]. INNs, by definition, are used globally, and it is possible that some drugs that have been classified as “not approved” in our analysis have been approved elsewhere in the world To support this statement, we searched different Web sites and databases[32] to investigate whether the molecules depicted in the figures of this review and not listed in the FDA, EMA, or PMDA sites had been authorized elsewhere in the world, and we found that a number of these are marketed (mainly in South America or the Far East).

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

Findings

■ REFERENCES