Triazoles in Medicinal Chemistry: Physicochemical Properties, Bioisosterism, and Application

Guan, Qianwen; Xing, Shuaishuai; Wang, Lei; Zhu, Jiawei; Guo, Can; Xu, Chunlei; Zhao, Qun; Wu, Yulan; Chen, Yao; Sun, Haopeng

doi:10.1021/acs.jmedchem.4c00652

Cited by 18 publications

(1 citation statement)

References 201 publications

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“…The 11th ranked nitrogen heterocycle is 1,2,4-triazole, with nine new small-molecule drugs (Figure ) along with the 1,2,3-triazole drugs daridorexant (approved 1/2022) and suvorexant (approved 8/2014), which are approved for hypotension and insomnia, respectively . This dataset includes the antifungal triazolium drug isavuconazonium (approved 3/2015) and the oxidized triazole HIV/AIDS drug doravirine (approved 8/2018).…”

Section: Us Fda-approved Nitrogen-containing Drugs (January 2013–dece...mentioning

confidence: 99%

An Update on the Nitrogen Heterocycle Compositions and Properties of U.S. FDA-Approved Pharmaceuticals (2013–2023)

Marshall,

Federice,

Bell

et al. 2024

J. Med. Chem.

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This Perspective is a continuation of our analysis of U.S. FDA-approved small-molecule drugs (1938−2012) containing nitrogen heterocycles. In this study we report drug structure and property analyses of 321 unique new small-molecule drugs approved from January 2013 to December 2023 as well as information about frequency of important heteroatoms such as sulfur and fluorine and key small nitrogen substituents (CN and NO 2 ). The most notable change is an incredible increase in drugs containing at least one nitrogen heterocycle�82%, compared to 59% from preceding decades�as well as a significant increase in the number of nitrogen heterocycles per drug. Pyridine has claimed the #1 high-frequency nitrogen heterocycle occurrence spot from piperidine (#2), with pyrimidine (#5), pyrazole (#6), and morpholine (#9) being the big top 10 climbers. Also notable is high number of fused nitrogen heterocycles, apparently driven largely by newly approved cancer drugs. ■ SIGNIFICANCEThis Perspective reinforces the significant role nitrogen heterocycles play as diverse tunable structural components of U.S. FDA-approved drugs (2013FDA-approved drugs ( −2023. This follow-up study reveals major increases in 1) the percentage of drugs containing a nitrogen heterocycle, 2) the number of nitrogen heterocycles per drug, and 3) the diversity of nitrogen heterocycles as well as the important roles fluorine and sulfur substituents continue to play. New atoms (B, D, and Si) are also introduced into this arena.

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Section: Us Fda-approved Nitrogen-containing Drugs (January 2013–dece...mentioning

confidence: 99%

An Update on the Nitrogen Heterocycle Compositions and Properties of U.S. FDA-Approved Pharmaceuticals (2013–2023)

Marshall,

Federice,

Bell

et al. 2024

J. Med. Chem.

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Mono‐ and bis(steroids) containing a cyclooctane core: Synthesis, antiproliferative activity, and action on cell cytoskeleton microtubules

Ryzhikova,

Churkina,

Sedenkova

et al. 2024

Archiv der Pharmazie

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Steroid dimers of natural and synthetic origin possess an unusual and complex molecular architecture that may lead to the realization of peculiar effects in biological systems, in particular in different cancer cell lines. In the present work, diastereoselective ring‐opening of mono‐ and polyoxiranes, containing a cyclooctane core, by azide‐anion was performed to yield a series of azidoalcohols with different types of symmetry. The products were involved in copper‐catalyzed azyde‐alkyne cycloaddition (CuAAC) reaction with ethinylestradiol and ethinyltestosterone, and the resulting steroids and steroid dimers with triazole linkers were screened for their antiproliferative activity via (3‐(4,5‐dimethylthiazol‐2‐yl)2,5‐diphenyl tetrazolium bromide) assay. All the compounds revealed cytotoxicity toward several cancer cell lines. The effect of the most potent compound, containing two estradiol moieties, on the microtubules (MT) dynamics was investigated by immunofluorescent microscopy. The disruption of the majority of interphase cell cytoplasmic MT and mitotic event disturbances in the presence of the studied compound were observed. The latter effect caused the appearance of numerous multinucleated cells.

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Molecular Interactions and Structural Transformations in Water Complexes with Azoles in Solid Films: IR and DFT Study

Kapustin,

Grinvald,

Agrba

et al. 2024

ChemistrySelect

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Azoles are widely used as bioactive substances, herbicides, catalysts, corrosion inhibitors, polymeric compositors, organometallic ligands, and optical elements’ components. The interaction with water plays a crucial role in many applications of azoles. The objective of this study is to observe the molecular interaction and structural transformations of 1,2‐ and 1,3‐diazoles’, 1,2,3‐ and 1,2,4‐triazoles’ complexes with water molecules. We have selected the most valuable for application and theoretical interest azoles with different molecular structures, which have allowed us to consider the basic features of their aqueous complexes. We used the IR study method allowing to fix water intermediates in the solid phase. We have also employed the hybrid B3LYP functional DFT method with GD3BJ dispersion correction. At the cluster formation, the hydrogen atom transfer arises, providing a labile spatial arrangement of the water system. The formation of azoles’ complexes with a hydronium ion having relatively low binding energy allows the reshaping of the complexes’ structure at the hydrogen atom cluster‐to‐cluster transition. The complex formation is accompanied by the hydrogen atom transfer with the participation of both water and azole hydrogen atoms. This transfer provides the mobile spatial arrangement of clusters and hydrogen atom transition from donor to acceptor centers.

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Triazoles in Medicinal Chemistry: Physicochemical Properties, Bioisosterism, and Application

Cited by 18 publications

References 201 publications

An Update on the Nitrogen Heterocycle Compositions and Properties of U.S. FDA-Approved Pharmaceuticals (2013–2023)

An Update on the Nitrogen Heterocycle Compositions and Properties of U.S. FDA-Approved Pharmaceuticals (2013–2023)

Mono‐ and bis(steroids) containing a cyclooctane core: Synthesis, antiproliferative activity, and action on cell cytoskeleton microtubules

Molecular Interactions and Structural Transformations in Water Complexes with Azoles in Solid Films: IR and DFT Study

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