FDA-approved heterocyclic molecules for cancer treatment: Synthesis, dosage, mechanism of action and their adverse effect

Abstract

As the incorporation of heterocycles increases the physical characteristics and biological activity of pharmacological molecules, heterocyclic scaffolds are commonly discovered as common cores in a wide spectrum of biologically active drugs. In the contemporary context, many heterocycles have arisen, playing vital roles in diverse pharmaceutical compounds that benefit humanity. Over 85 % of FDA-approved medication molecules contain heterocycles, and most importantly, numerous heterocyclic medicinal molecules indicate potential benefits against a range: of malignancies. The unique flexibility and dynamic core scaffold of these compounds have aided anticancer research. These medications are used to treat cancer patients by targeting particular genes, enzymes, and receptors. Aside from the drugs that are now on the market, numerous forms are being researched for their potential anti-cancer activity. Here in this review, we classified some molecules and biologically active heterocycles containing anticancer medicinal moieties approved by the FDA between 2019 and 2021 based on their use in various forms of cancer. We will focus on those that are suitable for cancer treatment, as well as the essential biochemical mechanisms of action, biological targets, synthetic methods, and inherent limiting considerations in their use.

Fig. 1

The active ingredients containing heterocyclic fragments of the top 5 small molecule drug brands by retail sales in 2022 worldwide.

Fig. 2

The worldwide estimated number of new incidents of all cancers, distributed by region, considering all ages and both genders in 2020.

Fig. 3

Worldwide crude incidence rates by type of cancer in all ages and both genders in 2020 (Excluding Non-melanoma skin cancers).

Fig. 4

Comparison of the crude incidence and mortality rates of males and females of all ages in the world in 2020 (Excluding Non-melanoma skin cancers).

Scheme 1

Synthesis of Alpelisib.

Scheme 2

Synthesis of Tucatinib.

Scheme 3

Synthesis of Entrectinib.

Scheme 4

Synthesis of Capmatinib.

Scheme 5

Synthesis of Pralsetinib.

Scheme 6

Synthesis of Tepotinib.

Scheme 7

Synthesis of Mobocertinib.

Scheme 8

Synthesis of Lurbinectedin.

Scheme 9

Synthesis of Trilaciclib.

Scheme 10

Synthesis of Darolutamide.

Scheme 11

Synthesis of Relugolix.

Scheme 12

Synthesis of Sotorasib.

Scheme 13

Synthesis of Selpercatinib.

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Synthesis of Avapritinib.

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Synthesis of Ripretinib.

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Synthesis of Tivozanib.

Scheme 17

Synthesis of Erdafitinib.

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Synthesis of Zanubrutinib.

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Synthesis of Umbralisib.

Scheme 20

Synthesis of Selinexor.

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Synthesis of Pemigatinib.

Scheme 22

Synthesis of Tazemetostat.

Scheme 23

Synthesis of Fedratinib.

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Synthesis of Decitabine using 5-azacytosine.

Scheme 25

Synthesis of Cedazuridine from Gemcitabine.

Scheme 26

Synthesis of Selumetinib.

Scheme 27

Synthesis of Piflufolastat F 18.