U.S. FDA Approved Drugs from 2015–June 2020: A Perspective

Abstract

In the present work, we report compilation and analysis of 245 drugs, including small and macromolecules approved by the U.S. FDA from 2015 until June 2020. Nearly 29% of the drugs were approved for the treatment of various types of cancers. Other major therapeutic areas of focus were infectious diseases (14%); neurological conditions (12%); and genetic, metabolic, and cardiovascular disorders (7−8% each). Itemization of the approved drugs according to the year of approval, sponsor, target, chemical class, major drug-metabolizing enzyme(s), route of administration/elimination, and drug−drug interaction liability (perpetrator or/and victim) is presented and discussed. An effort has been made to analyze the pharmacophores to identify the structural (e.g., aromatic, heterocycle, and aliphatic), elemental (e.g., boron, sulfur, fluorine, phosphorus, and deuterium), and functional group (e.g., nitro drugs) diversity among the approved drugs. Further, descriptor-based chemical space analysis of FDA approved drugs and several strategies utilized for optimizing metabolism leading to their discoveries have been emphasized. Finally, an analysis of drug-likeness for the approved drugs is presented.

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

“… 20 While this could be somehow expected, 36 the extent of the use of fluorine might possibly surprise some. Indeed, a recent analysis made on FDA-approved drugs from 2015 to 2020 showed that 26% of drugs displayed fluorine, 37 already a very high number, but in our analysis we find 40% of drugs in the same time frame (compared to 17% in the first four years of the century) and 55% of fluorinated drugs issued a name in 2020.…”

Design, Synthesis and Biological Evaluation of New 5‐(2‐Nitrophenyl)‐1‐aryl‐1H‐pyrazoles as Topoisomerase Inhibitors

“…[24] We recently analysed that nitrogen heterocyclics still hold the major share of small molecules in the US FDA approved drugs, including pyrazole, indazole, pyridine, etc. [25] Elexacaftor, darolutamide, zanubrutinib, erdafitinib, voxelotor and entrectinib are the FDA approved pyrazole-based drugs for the treatment of various diseases, including cancer, also (Figure 1). [25,26] Thus, the pyrazole ring has attracted much attention for the synthesis due to its diverse biological properties and accessibility.…”

“…[25] Elexacaftor, darolutamide, zanubrutinib, erdafitinib, voxelotor and entrectinib are the FDA approved pyrazole-based drugs for the treatment of various diseases, including cancer, also (Figure 1). [25,26] Thus, the pyrazole ring has attracted much attention for the synthesis due to its diverse biological properties and accessibility. [27] Teloxantrone and iosoxantrone are the important pyrazole-based topo II inhibitors that are under clinical trial.…”

“…It is found that these comprise mainly fluorine-containing molecules and aromatic nitrogen molecules like opicapone, risdiplam, remimazolam. [29] Similarly, after knowing the importance of various scaffolds, the addition of functional groups like nitro [25,30] to many N-heterocyclic scaffolds has successfully proved to impart better anticancer activity against various cell lines, and the results of the study demonstrated that the nitro group was of vital importance for the topoisomerase inhibition. [31] Recently our research group reported 2-nitro substituted Nacetyl/formyl pyrazolines [22,32] as effective anticancer agents, and interestingly compound 29 [22] showed topoisomerase inhibition as well.…”

“…To combat these limitations, researchers, including our research group, have identified and designed numerous Topo inhibitors [18,21,22] by modification of the existing Topo inhibitors such as camptothecin like molecules, novel N‐heterocyclic compounds, [23] derivatives of quinone, flavonoids, coumarin, lignan, polyphenol, diterpenes, fatty acids, and metal complexes [24] . We recently analysed that nitrogen heterocyclics still hold the major share of small molecules in the US FDA approved drugs, including pyrazole, indazole, pyridine, etc [25] …”