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19 pages, 2412 KiB

Open AccessArticle

N-Aryl Benzimidazole and Benzotriazole Derivatives and Their Hybrids as Cytotoxic Agents: Design, Synthesis and Structure–Activity Relationship Studies

by Yulia R. Aleksandrova, Natalia S. Nikolaeva, Inna A. Shagina, Karina D. Smirnova, Alla A. Zubishina, Alexander I. Khlopotinin, Artem N. Fakhrutdinov, Alexander L. Khokhlov, Roman S. Begunov and Margarita E. Neganova

Molecules 2024, 29(22), 5360; https://doi.org/10.3390/molecules29225360 - 14 Nov 2024

Viewed by 628

Abstract

The era of chemotherapy began in the 1940s, which is the basis of traditional antitumor approaches and, being one of the most high-tech treatment methods, is still widely used to treat various types of cancer. A promising direction in modern medicinal chemistry is [...] Read more.

The era of chemotherapy began in the 1940s, which is the basis of traditional antitumor approaches and, being one of the most high-tech treatment methods, is still widely used to treat various types of cancer. A promising direction in modern medicinal chemistry is currently the creation of hybrid molecules containing several pharmacophore fragments of different structures. This strategy is successfully used to increase the therapeutic efficacy of cytotoxic agents and reduce side effects. In this work, we synthesized 10 1-aryl derivatives of benzimidazole and benzotriazole and 11 hybrids based on them. Among the compounds obtained, the most promising hybrid molecules were diphenylamines, containing an amino group and a benzotriazole cycle in the ortho position to the bridging NH group, which showed significant cytotoxic activity, excellent antioxidant properties and the ability to suppress the migration activity of tumor cells. Taken together, our results demonstrate that substituted diphenylamine-based bipharmacophoric compounds may serve as a promising platform for further optimization to obtain effective antitumor compounds. Full article

(This article belongs to the Special Issue Synthesis and Properties of Heterocyclic Compounds: Recent Advances)

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24 pages, 3226 KiB

Open AccessArticle

Design, Synthesis, and Photophysical Properties of 5-Aminobiphenyl Substituted [1,2,4]Triazolo[4,3-c]- and [1,2,4]Triazolo[1,5-c]quinazolines

by Tatyana N. Moshkina, Alexandra E. Kopotilova, Marya A. Ivan’kina, Ekaterina S. Starnovskaya, Denis A. Gazizov, Emiliya V. Nosova, Dmitry S. Kopchuk, Oleg S. El’tsov, Pavel A. Slepukhin and Valery N. Charushin

Molecules 2024, 29(11), 2497; https://doi.org/10.3390/molecules29112497 - 24 May 2024

Cited by 1 | Viewed by 942

Abstract

Two series of novel [1,2,4]triazolo[4,3-c]- and [1,2,4]triazolo[1,5-c]quinazoline fluorophores with 4′-amino[1,1′]-biphenyl residue at position 5 have been prepared via Pd-catalyzed cross-coupling Suzuki–Miyaura reactions. The treatment of 2-(4-bromophenyl)-4-hydrazinoquinazoline with orthoesters in solvent-free conditions or in absolute ethanol leads to the formation [...] Read more.

Two series of novel [1,2,4]triazolo[4,3-c]- and [1,2,4]triazolo[1,5-c]quinazoline fluorophores with 4′-amino[1,1′]-biphenyl residue at position 5 have been prepared via Pd-catalyzed cross-coupling Suzuki–Miyaura reactions. The treatment of 2-(4-bromophenyl)-4-hydrazinoquinazoline with orthoesters in solvent-free conditions or in absolute ethanol leads to the formation of [4,3-c]-annulated triazoloquinazolines, whereas [1,5-c] isomers are formed in acidic media as a result of Dimroth rearrangement. A 1D-NMR and 2D-NMR spectroscopy, as well as a single-crystal X-ray diffraction analysis, unambiguously confirmed the annelation type and determined the molecular structure of p-bromophenyl intermediates and target products. Photophysical properties of the target compounds were investigated in two solvents and in the solid state and compared with those of related 3-aryl-substituted [1,2,4]triazolo[4,3-c]quinazolines. The exclusion of the aryl fragment from the triazole ring has been revealed to improve fluorescence quantum yield in solution. Most of the synthesized structures show moderate to high quantum yields in solution. Additionally, the effect of solvent polarity on the absorption and emission spectra of fluorophores has been studied, and considerable fluorosolvatochromism has been stated. Moreover, electrochemical investigation and DFT calculations have been performed; their results are consistent with the experimental observation. Full article

(This article belongs to the Special Issue Synthesis and Properties of Heterocyclic Compounds: Recent Advances)

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21 pages, 2955 KiB

Open AccessArticle

Synthesis of 5-(Aryl)amino-1,2,3-triazole-containing 2,1,3-Benzothiadiazoles via Azide–Nitrile Cycloaddition Followed by Buchwald–Hartwig Reaction

by Pavel S. Gribanov, Anna N. Philippova, Maxim A. Topchiy, Dmitry A. Lypenko, Artem V. Dmitriev, Sergey D. Tokarev, Alexander F. Smol’yakov, Alexey N. Rodionov, Andrey F. Asachenko and Sergey N. Osipov

Molecules 2024, 29(9), 2151; https://doi.org/10.3390/molecules29092151 - 6 May 2024

Cited by 1 | Viewed by 1607

Abstract

An efficient access to the novel 5-(aryl)amino-1,2,3-triazole-containing 2,1,3-benzothiadiazole derivatives has been developed. The method is based on 1,3-dipolar azide–nitrile cycloaddition followed by Buchwald–Hartwig cross-coupling to afford the corresponding N-aryl and N,N-diaryl substituted 5-amino-1,2,3-triazolyl 2,1,3-benzothiadiazoles under NHC-Pd catalysis. The one-pot [...] Read more.

An efficient access to the novel 5-(aryl)amino-1,2,3-triazole-containing 2,1,3-benzothiadiazole derivatives has been developed. The method is based on 1,3-dipolar azide–nitrile cycloaddition followed by Buchwald–Hartwig cross-coupling to afford the corresponding N-aryl and N,N-diaryl substituted 5-amino-1,2,3-triazolyl 2,1,3-benzothiadiazoles under NHC-Pd catalysis. The one-pot diarylative Pd-catalyzed heterocyclization opens the straightforward route to triazole-linked carbazole-benzothiadiazole D-A systems. The optical and electrochemical properties of the compound obtained were investigated to estimate their potential application as emissive layers in OLED devises. The quantum yield of photoluminescence (PLQY) of the synthesized D-A derivatives depends to a large extent on electron-donating strengths of donor (D) component, reaching in some cases the values closed to 100%. Based on the most photoactive derivative and wide bandgap host material mCP, a light-emitting layer of OLED was made. The device showed a maximum brightness of 8000 cd/m² at an applied voltage of 18 V. The maximum current efficiency of the device reaches a value of 3.29 cd/A. Full article

(This article belongs to the Special Issue Synthesis and Properties of Heterocyclic Compounds: Recent Advances)

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15 pages, 1589 KiB

Open AccessCommunication

Dearomatization of 3-Aminophenols for Synthesis of Spiro[chromane-3,1′-cyclohexane]-2′,4′-dien-6′-ones via Hydride Transfer Strategy-Enabled [5+1] Annulations

by Jia-Cheng Ge, Yufeng Wang, Feng-Wei Guo, Xiangyun Kong, Fangzhi Hu and Shuai-Shuai Li

Molecules 2024, 29(5), 1012; https://doi.org/10.3390/molecules29051012 - 26 Feb 2024

Cited by 1 | Viewed by 960

Abstract

The Sc(OTf)₃-catalyzed dearomative [5+1] annulations between readily available 3-aminophenols and O-alkyl ortho-oxybenzaldehydes were developed for synthesis of spiro[chromane-3,1′-cyclohexane]-2′,4′-dien-6′-ones. The “two-birds-with-one-stone” strategy was disclosed by the dearomatization of phenols and direct α-C(sp³)–H bond functionalization of oxygen through cascade [...] Read more.

The Sc(OTf)₃-catalyzed dearomative [5+1] annulations between readily available 3-aminophenols and O-alkyl ortho-oxybenzaldehydes were developed for synthesis of spiro[chromane-3,1′-cyclohexane]-2′,4′-dien-6′-ones. The “two-birds-with-one-stone” strategy was disclosed by the dearomatization of phenols and direct α-C(sp³)–H bond functionalization of oxygen through cascade condensation/[1,5]-hydride transfer/dearomative-cyclization process. In addition, the antifungal activity assay and derivatizations of products were conducted to further enrich the utility of the structure. Full article

(This article belongs to the Special Issue Synthesis and Properties of Heterocyclic Compounds: Recent Advances)

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12 pages, 2602 KiB

Open AccessCommunication

A Facile Ugi/Ullmann Cascade Reaction to Access Fused Indazolo-Quinoxaline Derivatives with Potent Anticancer Activity

by Yong Li, Liujun He, Hongxia Qin, Yao Liu, Binxin Yang, Zhigang Xu and Donglin Yang

Molecules 2024, 29(2), 464; https://doi.org/10.3390/molecules29020464 - 17 Jan 2024

Cited by 1 | Viewed by 1305

Abstract

A facile methodology for the construction of a complex heterocycle indazolo-fused quinoxalinone has been developed via an Ugi four-component reaction (U-4CR) followed by an intramolecular Ullmann reaction. The expeditious process features an operationally simple approach, time efficiency, and a broad substrate scope. Biological [...] Read more.

A facile methodology for the construction of a complex heterocycle indazolo-fused quinoxalinone has been developed via an Ugi four-component reaction (U-4CR) followed by an intramolecular Ullmann reaction. The expeditious process features an operationally simple approach, time efficiency, and a broad substrate scope. Biological activity was evaluated and demonstrated that compound 6e inhibits human colon cancer cell HCT116 proliferation with an IC₅₀ of 2.1 μM, suggesting potential applications for developing a drug lead in medicinal chemistry. Full article

(This article belongs to the Special Issue Synthesis and Properties of Heterocyclic Compounds: Recent Advances)

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22 pages, 7715 KiB

Open AccessArticle

Synthesis of Seven Indolizine-Derived Pentathiepines: Strong Electronic Structure Response to Nitro Substitution in Position C-9

by Roberto Tallarita, Lukas Manuel Jacobsen, Benedict J. Elvers, Stefan Richter, Siva S. M. Bandaru, Jevy V. Correia and Carola Schulzke

Molecules 2024, 29(1), 216; https://doi.org/10.3390/molecules29010216 - 30 Dec 2023

Cited by 2 | Viewed by 1290

Abstract

Seven new 1,2,3,4,5-pentathiepino[6,7-a]indolizines were synthesized in which the pentathiepine moieties bear an indolizine backbone that is derivatized from C–H to F-, Cl-, Br-, I-, NO₂-, and CH₃-substitutions, respectively, in a meta position relative to the aza group [...] Read more.

Seven new 1,2,3,4,5-pentathiepino[6,7-a]indolizines were synthesized in which the pentathiepine moieties bear an indolizine backbone that is derivatized from C–H to F-, Cl-, Br-, I-, NO₂-, and CH₃-substitutions, respectively, in a meta position relative to the aza group on the pyridine moiety. Their preparation took place via two common steps: (i) a Sonogashira coupling between (4-substituted) 2-bromo- or 2-chloropyridines and propynyl 3,3-diethylacetal, and (ii) a ring closing reaction mediated by a molybdenum oxo-bistetrasulfido complex and elemental sulfur. The latter simultaneously facilitates the 1,2,3,4,5-pentathiepino chain/ring- and indolizine ring-formations. The fluoro derivative was addressed with 2-bromo-5-aminopyridine as the starting material via a Sandmeyer reaction. The iodo derivative was obtained from 5-bromo-2-alkynylpiridine using a metal-assisted variation of the Finkelstein reaction. The requirement to explore different reaction conditions and the varied respective yields of the final products are discussed. The influence of the distinct substitutions on the pyridine moieties, their electronic structures, and respective chemical properties was investigated through a set of spectroscopic/analytical characterizations. Intriguingly, in all cases, the nitro-substituted derivative exhibited a distinct behavior compared to the six other investigated derivatives, which was also addressed computationally. All seven new pentathiepines were crystallized, and their respective molecular structures were determined using single crystal X-ray diffraction. These structures are compared and discussed as are their respective packing patterns. Full article

(This article belongs to the Special Issue Synthesis and Properties of Heterocyclic Compounds: Recent Advances)

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Review

Jump to: Research

18 pages, 4275 KiB

Open AccessReview

Recent Advances in the Synthesis of Rosettacin

by Xiao Tang, Yukang Jiang, Liangliang Song and Erik V. Van der Eycken

Molecules 2024, 29(10), 2176; https://doi.org/10.3390/molecules29102176 - 7 May 2024

Cited by 1 | Viewed by 853

Abstract

Camptothecin and its analogues show important antitumor activity and have been used in clinical studies. However, hydrolysis of lactone in the E ring seriously attenuates the antitumor activity. To change this situation, aromathecin alkaloids are investigated in order to replace camptothecins. Potential antitumor [...] Read more.

Camptothecin and its analogues show important antitumor activity and have been used in clinical studies. However, hydrolysis of lactone in the E ring seriously attenuates the antitumor activity. To change this situation, aromathecin alkaloids are investigated in order to replace camptothecins. Potential antitumor activity has obtained more and more attention from organic and pharmaceutical chemists. As a member of the aromathecin alkaloids, rosettacin has been synthesized via different methods. This review summarizes recent advances in the synthesis of rosettacin. Full article

(This article belongs to the Special Issue Synthesis and Properties of Heterocyclic Compounds: Recent Advances)

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19 pages, 8433 KiB

Open AccessReview

Recent Trends in the Petasis Reaction: A Review of Novel Catalytic Synthetic Approaches with Applications of the Petasis Reaction

by Sadaf Saeed, Saba Munawar, Sajjad Ahmad, Asim Mansha, Ameer Fawad Zahoor, Ali Irfan, Ahmad Irfan, Katarzyna Kotwica-Mojzych, Malgorzata Soroka, Mariola Głowacka and Mariusz Mojzych

Molecules 2023, 28(24), 8032; https://doi.org/10.3390/molecules28248032 - 10 Dec 2023

Cited by 2 | Viewed by 2253

Abstract

The Petasis reaction, also called the Petasis Borono–Mannich reaction, is a multicomponent reaction that couples a carbonyl derivative, an amine and boronic acids to yield substituted amines. The reaction proceeds efficiently in the presence or absence of a specific catalyst and solvent. By [...] Read more.

The Petasis reaction, also called the Petasis Borono–Mannich reaction, is a multicomponent reaction that couples a carbonyl derivative, an amine and boronic acids to yield substituted amines. The reaction proceeds efficiently in the presence or absence of a specific catalyst and solvent. By employing this reaction, a diverse range of chiral derivatives can easily be obtained, including α-amino acids. A broad substrate scope, high yields, distinct functional group tolerance and the availability of diverse catalytic systems constitute key features of this reaction. In this review article, attention has been drawn toward the recently reported methodologies for executing the Petasis reaction to produce structurally simple to complex aryl/allyl amino scaffolds. Full article

(This article belongs to the Special Issue Synthesis and Properties of Heterocyclic Compounds: Recent Advances)

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