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Heterocyclic Compounds (Closed)

A topical collection in Molecules (ISSN 1420-3049). This collection belongs to the section "Organic Chemistry".

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Editors


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Collection Editor
Department of Chemistry, Oklahoma State University, Stillwater, OK 74078-3071, USA
Interests: heterocycles; antibacterial agents; anticancer agents; enzyme inhibitors; medicinal chemistry; drug discovery; drug development; synthetic methodology
Special Issues, Collections and Topics in MDPI journals

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Collection Editor
School of Pharmacy, University Paris Descartes, UMR CNRS 8638, case 24. 4, avenue de l’Observatoire, 75006 Paris, France
Interests: heterocyclic synthesis; nitrogen-containing heterocycles; methodologies using organic or organometallic reagents; organometallic catalysis; cyclo-isomerization reactions; cyclo-functionalization reactions; benzannulation; aminobenzannulation; pi-acid metal catalysis; silver chemistry; gold chemistry; cobalt chemistry; Pauson-Khand reaction; bioactive compounds; alkaloids; kinases inhibition
Special Issues, Collections and Topics in MDPI journals

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Collection Editor
Department of Chemistry, Celestijnenlaan 200F, B-3001 Leuven, Belgium
Interests: organic synthesis; heterocycles; supramolecular chemistry; porphyrin analogues; natural products; helicenes
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

Heterocyclic compounds are an important class of molecules in organic chemistry, due to their presence in natural products and their use in pharmaceuticals and new materials. Heterocycles are the key to biological activity in many small molecule drugs, due to their ability to hydrogen bond, alter polarity, and modulate lipophilicity at specific sites in the pathogen or host, with the overall effect of inhibiting the biological processes that lead to the programmed progressions of diseases. Similar advantages can be cited in the area of materials chemistry, as heterocycles can impart unique properties to new materials, due to their polarity, solubility, and their electronic and optical properties. In this Molecules Topical Collection, entitled "Heterocyclic Compounds", we invite manuscript submissions that focus on the synthesis of natural and unnatural heterocyclic compounds and their potential uses in medicinal and materials chemistry. It is expected that most submissions will focus on nitrogen, oxygen, and sulfur heterocycles, but structures incorporating other heteroatoms will also be considered. Original research articles or reviews that discuss synthetic methodologies for preparing heterocyclic compounds, total synthesis, and structure studies of heterocycle-containing substances, as well as potential new applications to medicinal and materials chemistry, are particularly welcome.

Prof. Dr. Richard A. Bunce
Prof. Dr. Philippe Belmont
Prof. Dr. Wim Dehaen
Prof. Dr. Eugene Babaev
Collection Editors

Manuscript Submission Information

Manuscripts for the topical collection can be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on this website. The topical collection considers regular research articles, short communications and review articles. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page.

Please visit the Instructions for Authors page before submitting a manuscript. The article processing charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs).

Keywords

  • new synthetic approaches to heterocycles
  • synthesis of heterocyclic natural products
  • biologically active heterocycles
  • medicinal studies of heterocycles
  • structure-activity relationships of drugs containing heterocycles
  • new heterocycle-based materials
  • structure-property relationships of materials containing heterocycles
  • heterocycles with unique properties
  • applications of heterocycle-based materials

Published Papers (127 papers)

2023

Jump to: 2022, 2021, 2020, 2019, 2018, 2017, 2016, 2015

11 pages, 1110 KiB  
Article
Synthesis of New Polyheterocyclic Pyrrolo[3,4-b]pyridin-5-ones via an Ugi-Zhu/Cascade/Click Strategy
by Roberto E. Blanco-Carapia, Enrique A. Aguilar-Rangel, Mónica A. Rincón-Guevara, Alejandro Islas-Jácome and Eduardo González-Zamora
Molecules 2023, 28(10), 4087; https://doi.org/10.3390/molecules28104087 - 14 May 2023
Cited by 1 | Viewed by 1527
Abstract
A diversity-oriented synthesis (DOS) of two new polyheterocyclic compounds was performed via an Ugi-Zhu/cascade (N-acylation/aza Diels-Alder cycloaddition/decarboxylation/dehydration)/click strategy, both step-by-step to optimize all involved experimental stages, and in one pot manner to evaluate the scope and sustainability of this polyheterocyclic-focused [...] Read more.
A diversity-oriented synthesis (DOS) of two new polyheterocyclic compounds was performed via an Ugi-Zhu/cascade (N-acylation/aza Diels-Alder cycloaddition/decarboxylation/dehydration)/click strategy, both step-by-step to optimize all involved experimental stages, and in one pot manner to evaluate the scope and sustainability of this polyheterocyclic-focused synthetic strategy. In both ways, the yields were excellent, considering the high number of bonds formed with release of only one carbon dioxide and two molecules of water. The Ugi-Zhu reaction was carried out using the 4-formylbenzonitrile as orthogonal reagent, where the formyl group was first transformed into the pyrrolo[3,4-b]pyridin-5-one core, and then the remaining nitrile group was further converted into two different nitrogen-containing polyheterocycles, both via click-type cycloadditions. The first one used sodium azide to obtain the corresponding 5-substituted-1H-tetrazolyl-pyrrolo[3,4-b]pyridin-5-one, and the second one with dicyandiamide to synthesize the 2,4-diamino-1,3,5-triazine-pyrrolo[3,4-b]pyridin-5-one. Both synthesized compounds may be used for further in vitro and in silico studies because they contain more than two heterocyclic moieties of high interest in medicinal chemistry, as well as in optics due to their high π-conjugation. Full article
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12 pages, 1746 KiB  
Article
Macrocycle with Equatorial Coordination Sites Provides New Opportunity for Structure-Diverse Metallacages
by Yibo Zhao, Yunfeng Lu, Ao Liu, Zhi-Yuan Zhang, Chunju Li and Andrew C.-H. Sue
Molecules 2023, 28(6), 2537; https://doi.org/10.3390/molecules28062537 - 10 Mar 2023
Cited by 2 | Viewed by 1893
Abstract
Reported here is the synthesis of a macrocycle with equatorial coordination sites for the construction of self-assembled metallacages. The macrocycle is prepared via a post-modification on the equator of biphen[n]arene. Utilizing this macrocycle as a ligand, three prismatic cages and one [...] Read more.
Reported here is the synthesis of a macrocycle with equatorial coordination sites for the construction of self-assembled metallacages. The macrocycle is prepared via a post-modification on the equator of biphen[n]arene. Utilizing this macrocycle as a ligand, three prismatic cages and one octahedral cage were synthesized by regulating the geometric structures and coordination number of metal acceptors. The multi-cavity configuration of prismatic cage was revealed by single-crystal structure. We prove that a macrocycle with equatorial coordination sites can be an excellent building block for synthesizing structure-diverse metallacages. Our results provide a typical example and a general method for the design and synthesis of metallacages. Full article
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2022

Jump to: 2023, 2021, 2020, 2019, 2018, 2017, 2016, 2015

23 pages, 6098 KiB  
Article
Synthesis, Structure and Photochemistry of Dibenzylidenecyclobutanones
by Marina V. Fomina, Alexandra Y. Freidzon, Lyudmila G. Kuz’mina, Anna A. Moiseeva, Roman O. Starostin, Nikolai A. Kurchavov, Vyacheslav N. Nuriev and Sergey P. Gromov
Molecules 2022, 27(21), 7602; https://doi.org/10.3390/molecules27217602 - 5 Nov 2022
Cited by 2 | Viewed by 1795
Abstract
A series of symmetrical dibenzylidene derivatives of cyclobutanone were synthesized with the goal of studying the physicochemical properties of cross-conjugated dienones (ketocyanine dyes). The structures of the products were established and studied by X-ray diffraction and by NMR and electronic spectroscopy. All the [...] Read more.
A series of symmetrical dibenzylidene derivatives of cyclobutanone were synthesized with the goal of studying the physicochemical properties of cross-conjugated dienones (ketocyanine dyes). The structures of the products were established and studied by X-ray diffraction and by NMR and electronic spectroscopy. All the products had E,E-geometry. The oxidation and reduction potentials of the dienones were determined by cyclic voltammetry. The potentials were shown to depend on the nature, position, and number of substituents in the benzene rings. A linear correlation was found between the difference of the electrochemical oxidation and reduction potentials and the energy of the long-wavelength absorption maximum. This correlation can be employed to analyze the properties of other compounds of this type. Quantum chemistry was used to explain the observed regularities in the electrochemistry, absorption, and fluorescence of the dyes. The results are in good agreement with the experimental redox potentials and spectroscopy data. Full article
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16 pages, 5349 KiB  
Article
Experimental and Computational Analysis of Newly Synthesized Benzotriazinone Sulfonamides as Alpha-Glucosidase Inhibitors
by Zunera Khalid, Maha Abdallah Alnuwaiser, Hafiz Adnan Ahmad, Syed Salman Shafqat, Munawar Ali Munawar, Kashif Kamran, Muhammad Mujtaba Abbas, M. A. Kalam and Menna A. Ewida
Molecules 2022, 27(20), 6783; https://doi.org/10.3390/molecules27206783 - 11 Oct 2022
Cited by 4 | Viewed by 1850
Abstract
Diabetes mellitus is a chronic metabolic disorder in which the pancreas secretes insulin but the body cells do not recognize it. As a result, carbohydrate metabolism causes hyperglycemia, which may be fatal for various organs. This disease is increasing day by day and [...] Read more.
Diabetes mellitus is a chronic metabolic disorder in which the pancreas secretes insulin but the body cells do not recognize it. As a result, carbohydrate metabolism causes hyperglycemia, which may be fatal for various organs. This disease is increasing day by day and it is prevalent among people of all ages, including young adults and children. Acarbose and miglitol are famous alpha-glucosidase inhibitors but they complicate patients with the problems of flatulence, pain, bloating, diarrhea, and loss of appetite. To overcome these challenges, it is crucial to discover new anti-diabetic drugs with minimal side effects. For this purpose, benzotriazinone sulfonamides were synthesized and their structures were characterized by FT-IR, 1H-NMR and 13C-NMR spectroscopy. In vitro alpha-glucosidase inhibition studies of all synthesized hybrids were conducted using the spectrophotometric method. The synthesized compounds revealed moderate-to-good inhibition activity; in particular, nitro derivatives 12e and 12f were found to be the most effective inhibitors against this enzyme, with IC50 values of 32.37 ± 0.15 µM and 37.75 ± 0.11 µM. In silico studies, including molecular docking as well as DFT analysis, also strengthened the experimental findings. Both leading compounds 12e and 12f showed strong hydrogen bonding interactions within the enzyme cavity. DFT studies also reinforced the strong binding interactions of these derivatives with biological molecules due to their lowest chemical hardness values and lowest orbital energy gap values. Full article
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15 pages, 31883 KiB  
Article
Synthesis, Experimental and Theoretical Study of Azidochromones
by Ena G. Narváez-Ordoñez, Kevin A. Pabón-Carcelén, Daniel A. Zurita-Saltos, Pablo M. Bonilla-Valladares, Trosky G. Yánez-Darquea, Luis A. Ramos-Guerrero, Sonia E. Ulic, Jorge L. Jios, Gustavo A. Echeverría, Oscar E. Piro, Peter Langer, Christian D. Alcívar-León and Jorge Heredia-Moya
Molecules 2022, 27(9), 2636; https://doi.org/10.3390/molecules27092636 - 20 Apr 2022
Cited by 1 | Viewed by 2382
Abstract
A series of 2-(haloalkyl)-3-azidomethyl and 6-azido chromones has been synthetized, characterized and studied by theoretical (DFT calculations) and spectroscopic methods (UV-Vis, NMR). The crystal structure of 3-azidomethyl-2-difluoromethyl chromone, determined by X-ray diffraction methods, shows a planar framework due to extended π-bond delocalization. Its [...] Read more.
A series of 2-(haloalkyl)-3-azidomethyl and 6-azido chromones has been synthetized, characterized and studied by theoretical (DFT calculations) and spectroscopic methods (UV-Vis, NMR). The crystal structure of 3-azidomethyl-2-difluoromethyl chromone, determined by X-ray diffraction methods, shows a planar framework due to extended π-bond delocalization. Its molecular packing is stabilized by F···H, N···H and O···H hydrogen bonds, π···π stacking and C–O···π intermolecular interactions. Moreover, AIM, NCI and Hirshfeld analysis evidenced that azido moiety has a significant role in the stabilization of crystal packing through weak intermolecular interactions, where analysis of electronic density suggested closed-shell (CS) interatomic interactions. Full article
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12 pages, 2772 KiB  
Article
Total Synthesis of Eliglustat via Diastereoselective Amination of Chiral para-Methoxycinnamyl Benzyl Ether
by Younggyu Kong, Pulla Reddy Boggu, Gi Min Park, Yeon Su Kim, Seong Hwan An, In Su Kim and Young Hoon Jung
Molecules 2022, 27(8), 2603; https://doi.org/10.3390/molecules27082603 - 18 Apr 2022
Cited by 2 | Viewed by 2734
Abstract
Eliglustat (Cerdelga®, Genzyme Corp. Cambridge, MA, USA) is an approved drug for a non-neurological type of Gaucher disease. Herein, we describe the total synthesis of eliglustat 1 starting from readily available 1,4-benzodioxan-6-carbaldehyde via Sharpless asymmetric dihydroxylation and diastereoselective amination of chiral [...] Read more.
Eliglustat (Cerdelga®, Genzyme Corp. Cambridge, MA, USA) is an approved drug for a non-neurological type of Gaucher disease. Herein, we describe the total synthesis of eliglustat 1 starting from readily available 1,4-benzodioxan-6-carbaldehyde via Sharpless asymmetric dihydroxylation and diastereoselective amination of chiral para-methoxycinnamyl benzyl ethers using chlorosulfonyl isocyanate as the key steps. Notably, the reaction between syn-1,2-dibenzyl ether 6 and chlorosulfonyl isocyanate in the mixture of toluene and hexane (10:1) afforded syn-1,2-amino alcohol 5 at a 62% yield with a diastereoselectivity > 20:1. This observation can be explained by competition between the SNi and the SN1 mechanisms, leading to the retention of stereochemistry. Full article
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13 pages, 2006 KiB  
Article
3,4-Unsubstituted 2-tert-Butyl-pyrrolidine-1-oxyls with Hydrophilic Functional Groups in the Side Chains
by Andrey I. Taratayko, Yurii I. Glazachev, Ilia V. Eltsov, Elena I. Chernyak and Igor A. Kirilyuk
Molecules 2022, 27(6), 1922; https://doi.org/10.3390/molecules27061922 - 16 Mar 2022
Cited by 5 | Viewed by 1901
Abstract
Pyrrolidine nitroxides with four bulky alkyl substituents adjacent to N–O group are known for their high resistance to bioreduction. The 3,4-unsubstituted 2-tert-butyl-2-ethylpyrrolidine-1-oxyls were prepared from the corresponding 2-tert-butyl-1-pyrroline-1-oxides via either the addition of ethinylmagnesium bromide with subsequent hydrogenation or [...] Read more.
Pyrrolidine nitroxides with four bulky alkyl substituents adjacent to N–O group are known for their high resistance to bioreduction. The 3,4-unsubstituted 2-tert-butyl-2-ethylpyrrolidine-1-oxyls were prepared from the corresponding 2-tert-butyl-1-pyrroline-1-oxides via either the addition of ethinylmagnesium bromide with subsequent hydrogenation or via treatment with ethyllithium. The new nitroxides showed excellent stability to reduction with ascorbate with no evidence for additional large hyperfine couplings in the EPR spectra. Full article
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13 pages, 6496 KiB  
Article
Synthesis and Fluorescent Properties of Aminopyridines and the Application in “Click and Probing”
by Zongyang Li, Yaxuan Li, Wenxu Chang, Sen Pang, Xuefeng Li, Liusheng Duan and Zhenhua Zhang
Molecules 2022, 27(5), 1596; https://doi.org/10.3390/molecules27051596 - 28 Feb 2022
Cited by 2 | Viewed by 1951
Abstract
Unsubstituted pyridin-2-amine has a high quantum yield and is a potential scaffold for a fluorescent probe. However, the facile access to conjugated highly substituted aminopyridines and the study of their fluorescent properties is scarce. In this paper, synthesis and fluorescent properties of multisubstituted [...] Read more.
Unsubstituted pyridin-2-amine has a high quantum yield and is a potential scaffold for a fluorescent probe. However, the facile access to conjugated highly substituted aminopyridines and the study of their fluorescent properties is scarce. In this paper, synthesis and fluorescent properties of multisubstituted aminopyridines were studied based on a recently developed Rh-catalyzed coupling of vinyl azide with isonitrile to form a vinyl carbodiimide intermediate, following tandem cyclization with an alkyne. An aminopyridine substituted with an azide group as a potential probe was further designed, synthesized, and evaluated. The “clicking-and-probing” experiment of it on BSA protein showed the potential of aminopyridine as a scaffold of a biological probe. Full article
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2021

Jump to: 2023, 2022, 2020, 2019, 2018, 2017, 2016, 2015

9 pages, 1821 KiB  
Communication
BN-Embedded Perylenes
by Xiangdong Fang
Molecules 2021, 26(23), 7148; https://doi.org/10.3390/molecules26237148 - 25 Nov 2021
Cited by 6 | Viewed by 3186
Abstract
Transition metal catalyzed coupling reaction strategy has been utilized in the synthesis of two novel BN-perylenes starting from halogenated BN-naphthalene derivatives. The molecular structures and packing modes of BN-perylenes were confirmed by NMR spectroscopy and X-ray single-crystal diffraction experiments. Their photophysical properties were [...] Read more.
Transition metal catalyzed coupling reaction strategy has been utilized in the synthesis of two novel BN-perylenes starting from halogenated BN-naphthalene derivatives. The molecular structures and packing modes of BN-perylenes were confirmed by NMR spectroscopy and X-ray single-crystal diffraction experiments. Their photophysical properties were further investigated using UV-vis and fluorescence spectroscopy and DFT calculations. Interestingly, the isosteric BN-insertion in perylene system resulted in stronger π-π stacking interaction both in solid and solution phases. The synthesized BN-perylenes are proved to be highly stable and thus provide a new valuable platform for novel organic materials applications which is otherwise inaccessible to date. Full article
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28 pages, 22086 KiB  
Article
Studies towards the Design and Synthesis of Novel 1,5-Diaryl-1H-imidazole-4-carboxylic Acids and 1,5-Diaryl-1H-imidazole-4-carbohydrazides as Host LEDGF/p75 and HIV-1 Integrase Interaction Inhibitors
by Thompho J. Rashamuse, Muhammad Q. Fish, E. Mabel Coyanis and Moira L. Bode
Molecules 2021, 26(20), 6203; https://doi.org/10.3390/molecules26206203 - 14 Oct 2021
Cited by 8 | Viewed by 2325
Abstract
Two targeted sets of novel 1,5-diaryl-1H-imidazole-4-carboxylic acids 10 and carbohydrazides 11 were designed and synthesized from their corresponding ester intermediates 17, which were prepared via cycloaddition of ethyl isocyanoacetate 16 and diarylimidoyl chlorides 15. Evaluation of these new target [...] Read more.
Two targeted sets of novel 1,5-diaryl-1H-imidazole-4-carboxylic acids 10 and carbohydrazides 11 were designed and synthesized from their corresponding ester intermediates 17, which were prepared via cycloaddition of ethyl isocyanoacetate 16 and diarylimidoyl chlorides 15. Evaluation of these new target scaffolds in the AlphaScreenTM HIV-1 IN-LEDGF/p75 inhibition assay identified seventeen compounds exceeding the pre-defined 50% inhibitory threshold at 100 µM concentration. Further evaluation of these compounds in the HIV-1 IN strand transfer assay at 100 μM showed that none of the compounds (with the exception of 10a, 10l, and 11k, with marginal inhibitory percentages) were actively bound to the active site, indicating that they are selectively binding to the LEDGF/p75-binding pocket. In a cell-based HIV-1 antiviral assay, compounds 11a, 11b, 11g, and 11h exhibited moderate antiviral percentage inhibition of 33–45% with cytotoxicity (CC50) values of >200 µM, 158.4 µM, >200 µM, and 50.4 µM, respectively. The antiviral inhibitory activity displayed by 11h was attributed to its toxicity. Upon further validation of their ability to induce multimerization in a Western blot gel assay, compounds 11a, 11b, and 11h appeared to increase higher-order forms of IN. Full article
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19 pages, 2106 KiB  
Article
Synthesis of 6-Membered-Ring Fused Thiazine-Dicarboxylates and Thiazole-Pyrimidines via One-Pot Three-Component Reactions
by Reagan L. Mohlala, Elena Mabel Coyanis, Muhammad Q. Fish, Manuel A. Fernandes and Moira L. Bode
Molecules 2021, 26(18), 5493; https://doi.org/10.3390/molecules26185493 - 10 Sep 2021
Cited by 6 | Viewed by 2517
Abstract
A facile and efficient one-pot three-component reaction method for the synthesis of thiazine-dicarboxylates is reported. Reaction of an isocyanide and dialkyl acetylenedicarboxylate with 2-amino-4H-1,3-thiazin-4-one derivatives containing both an acidic proton and an internal nucleophile gave the products in good yields of [...] Read more.
A facile and efficient one-pot three-component reaction method for the synthesis of thiazine-dicarboxylates is reported. Reaction of an isocyanide and dialkyl acetylenedicarboxylate with 2-amino-4H-1,3-thiazin-4-one derivatives containing both an acidic proton and an internal nucleophile gave the products in good yields of 76–85%. The reactivity of dialkyl acetylenedicarboxylates was further tested in the synthesis of thiazole-pyrimidines where a two-component reaction of 2-aminothiazole with dialkyl acetylenedicarboxylates was successfully converted to a more efficient three-component reaction of a thiourea, α-haloketone and dialkyl acetylenedicarboxylate (DMAD/DEtAD) to give thiazole-pyrimidines in good yields of 70–91%. Full article
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28 pages, 40332 KiB  
Review
4,5,6,7-Tetrahydroindol-4-Ones as a Valuable Starting Point for the Synthesis of Polyheterocyclic Structures
by Tomas Horsten and Wim Dehaen
Molecules 2021, 26(15), 4596; https://doi.org/10.3390/molecules26154596 - 29 Jul 2021
Cited by 4 | Viewed by 2853
Abstract
This review focuses on the synthesis of polyheterocyclic structures with a variety of medicinal and optoelectronic applications, starting from readily available 4,5,6,7-tetrahydroindol-4-one analogs. First, routes toward the 4,5,6,7-tetrahydroindol-4-one starting materials are summarized, followed by synthetic pathways towards polyheterocyclic structures which are categorized based [...] Read more.
This review focuses on the synthesis of polyheterocyclic structures with a variety of medicinal and optoelectronic applications, starting from readily available 4,5,6,7-tetrahydroindol-4-one analogs. First, routes toward the 4,5,6,7-tetrahydroindol-4-one starting materials are summarized, followed by synthetic pathways towards polyheterocyclic structures which are categorized based on the size and attachment point of the newly formed (hetero)cyclic ring. Full article
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10 pages, 1496 KiB  
Article
3-Benzoylisoxazolines by 1,3-Dipolar Cycloaddition: Chloramine-T-Catalyzed Condensation of α-Nitroketones with Dipolarophiles
by Xinhui Pan, Xiaobing Xin, Ying Mao, Xin Li, Yanan Zhao, Yidi Liu, Ke Zhang, Xiaoda Yang and Jinhui Wang
Molecules 2021, 26(12), 3491; https://doi.org/10.3390/molecules26123491 - 8 Jun 2021
Cited by 5 | Viewed by 2440
Abstract
In this study, 3-benzoylisoxazolines were synthesized by reacting alkenes with various α-nitroketones using chloramine-T as the base. The scope of α-nitroketones and alkenes is extensive, including different alkenes and alkynes to form various isoxazolines and isoxazoles. The use of chloramine-T, as the low-cost, [...] Read more.
In this study, 3-benzoylisoxazolines were synthesized by reacting alkenes with various α-nitroketones using chloramine-T as the base. The scope of α-nitroketones and alkenes is extensive, including different alkenes and alkynes to form various isoxazolines and isoxazoles. The use of chloramine-T, as the low-cost, easily handled, moderate base for 1,3-dipolar cycloaddition is attractive. Full article
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20 pages, 4683 KiB  
Article
Synthesis and Rational Design of New Appended 1,2,3-Triazole-uracil Ensembles as Promising Anti-Tumor Agents via In Silico VEGFR-2 Transferase Inhibition
by Nadipolla Naresh Reddy, Sung-Jen Hung, Merugu Kumara Swamy, Ananthula Sanjeev, Vankadari Srinivasa Rao, Rondla Rohini, Atcha Krishnam Raju, Kuthati Bhaskar, Anren Hu and Puchakayala Muralidhar Reddy
Molecules 2021, 26(7), 1952; https://doi.org/10.3390/molecules26071952 - 30 Mar 2021
Cited by 8 | Viewed by 2527
Abstract
Angiogenesis inhibition is a key step towards the designing of new chemotherapeutic agents. In a view to preparing new molecular entities for cancer treatment, eighteen 1,2,3-triazole-uracil ensembles 5ar were designed and synthesized via the click reaction. The ligands were well characterized [...] Read more.
Angiogenesis inhibition is a key step towards the designing of new chemotherapeutic agents. In a view to preparing new molecular entities for cancer treatment, eighteen 1,2,3-triazole-uracil ensembles 5ar were designed and synthesized via the click reaction. The ligands were well characterized using 1H-, 13C-NMR, elemental analysis and ESI-mass spectrometry. The in silico binding propinquities of the ligands were studied sequentially in the active region of VEGFR-2 using the Molegro virtual docker. All the compounds produced remarkable interactions and potentially inhibitory ligands against VEGFR-2 were obtained with high negative binding energies. Drug-likeness was assessed from the ADME properties. Cytotoxicity of the test compounds was measured against HeLa and HUH-7 tumor cells and NIH/3T3 normal cells by MTT assay. Compound 5h showed higher growth inhibition activity than the positive control, 5-fluorouracil (5-FU), against both HeLa and HUH-7 cells with IC50 values of 4.5 and 7.7 μM respectively. Interestingly, the compounds 5ar did not show any cytotoxicity towards the normal cell lines. The results advance the position of substituted triazoles in the area of drug design with no ambiguity. Full article
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22 pages, 10490 KiB  
Article
Dihydroquinolines, Dihydronaphthyridines and Quinolones by Domino Reactions of Morita-Baylis-Hillman Acetates
by Joel K. Annor-Gyamfi, Ebenezer Ametsetor, Kevin Meraz and Richard A. Bunce
Molecules 2021, 26(4), 890; https://doi.org/10.3390/molecules26040890 - 8 Feb 2021
Cited by 3 | Viewed by 2392
Abstract
An efficient synthetic route to highly substituted dihydroquinolines and dihydronaphthyridines has been developed using a domino reaction of Morita-Baylis-Hillman (MBH) acetates with primary aliphatic and aromatic amines in DMF at 50–90 °C. The MBH substrates incorporate a side chain acetate positioned adjacent to [...] Read more.
An efficient synthetic route to highly substituted dihydroquinolines and dihydronaphthyridines has been developed using a domino reaction of Morita-Baylis-Hillman (MBH) acetates with primary aliphatic and aromatic amines in DMF at 50–90 °C. The MBH substrates incorporate a side chain acetate positioned adjacent to an acrylate or acrylonitrile aza-Michael acceptor as well as an aromatic ring activated toward SNAr ring closure. A control experiment established that the initial reaction was an SN2′-type displacement of the side chain acetate by the amine to generate the alkene product with the added nitrogen nucleophile positioned trans to the SNAr aromatic ring acceptor. Thus, equilibration of the initial alkene geometry is required prior to cyclization. A further double bond migration was observed for several reactions targeting dihydronaphthyridines from substrates with a side chain acrylonitrile moiety. MBH acetates incorporating a 2,5-difluorophenyl moiety were found to have dual reactivity in these annulations. In the absence of O2, the expected dihydroquinolines were formed, while in the presence of O2, quinolones were produced. All of the products were isolated in good to excellent yields (72–93%). Numerous cases (42) are reported, and mechanisms are discussed. Full article
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2020

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16 pages, 1483 KiB  
Article
A General and Scalable Synthesis of Polysubstituted Indoles
by David Tejedor, Raquel Diana-Rivero and Fernando García-Tellado
Molecules 2020, 25(23), 5595; https://doi.org/10.3390/molecules25235595 - 28 Nov 2020
Cited by 4 | Viewed by 3179
Abstract
A consecutive 2-step synthesis of N-unprotected polysubstituted indoles bearing an electron-withdrawing group at the C-3 position from readily available nitroarenes is reported. The protocol is based on the [3,3]-sigmatropic rearrangement of N-oxyenamines generated by the DABCO-catalyzed reaction of N-arylhydroxylamines and [...] Read more.
A consecutive 2-step synthesis of N-unprotected polysubstituted indoles bearing an electron-withdrawing group at the C-3 position from readily available nitroarenes is reported. The protocol is based on the [3,3]-sigmatropic rearrangement of N-oxyenamines generated by the DABCO-catalyzed reaction of N-arylhydroxylamines and conjugated terminal alkynes, and delivers indoles endowed with a wide array of substitution patterns and topologies. Full article
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75 pages, 27336 KiB  
Review
Synthetic Strategies, Reactivity and Applications of 1,5-Naphthyridines
by Maria Fuertes, Carme Masdeu, Endika Martin-Encinas, Asier Selas, Gloria Rubiales, Francisco Palacios and Concepcion Alonso
Molecules 2020, 25(14), 3252; https://doi.org/10.3390/molecules25143252 - 16 Jul 2020
Cited by 7 | Viewed by 5124
Abstract
This review covers the synthesis and reactivity of 1,5-naphthyridine derivatives published in the last 18 years. These heterocycles present a significant importance in the field of medicinal chemistry because many of them exhibit a great variety of biological activities. First, the published strategies [...] Read more.
This review covers the synthesis and reactivity of 1,5-naphthyridine derivatives published in the last 18 years. These heterocycles present a significant importance in the field of medicinal chemistry because many of them exhibit a great variety of biological activities. First, the published strategies related to the synthesis of 1,5-naphthyridines are presented followed by the reactivity of these compounds with electrophilic or nucleophilic reagents, in oxidations, reductions, cross-coupling reactions, modification of side chains or formation of metal complexes. Finally, some properties and applications of these heterocycles studied during this period are examined. Full article
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10 pages, 1423 KiB  
Communication
Two Annulated Azaheterocyclic Cores Readily Available from a Single Tetrahydroisoquinolonic Castagnoli–Cushman Precursor
by Elizaveta Karchuganova, Olga Bakulina, Dmitry Dar’in and Mikhail Krasavin
Molecules 2020, 25(9), 2049; https://doi.org/10.3390/molecules25092049 - 28 Apr 2020
Cited by 2 | Viewed by 2700
Abstract
A novel approach to indolo[3,2-c]isoquinoline and dibenzo[c,h][1,6]naphthyridine tetracyclic systems was discovered based on switchable reduction of 2-methoxy-3-(2-nitrophenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid prepared via Castagnoli–Cushman reaction. Reduction with ammonium formate resulted in the expected selective transformation of the nitro group (thus [...] Read more.
A novel approach to indolo[3,2-c]isoquinoline and dibenzo[c,h][1,6]naphthyridine tetracyclic systems was discovered based on switchable reduction of 2-methoxy-3-(2-nitrophenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid prepared via Castagnoli–Cushman reaction. Reduction with ammonium formate resulted in the expected selective transformation of the nitro group (thus providing access to substituted dibenzo[c,h][1,6]naphthyridine via cyclization and dehydrogenation). However, attempted reduction with sodium sulfide initiated a previously unknown reaction cascade including double reduction, cyclization, and decarboxylation, leading to formation of indolo[3,2-c]isoquinoline polyheterocycle in one synthetic step. Full article
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14 pages, 2630 KiB  
Article
Synthesis and Antibacterial Evaluation of Novel 1,3,4-Oxadiazole Derivatives Containing Sulfonate/Carboxylate Moiety
by Lei Wang, Xia Zhou, Hui Lu, Xianfu Mu and Linhong Jin
Molecules 2020, 25(7), 1488; https://doi.org/10.3390/molecules25071488 - 25 Mar 2020
Cited by 6 | Viewed by 3013
Abstract
In order to discover new lead compounds with high antibacterial activity, a series of new derivatives were designed and synthesized by introducing a sulfonate or carboxylate moiety into the 1,3,4-oxadiazole structure. Antibacterial activity against two phytopathogens, Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas [...] Read more.
In order to discover new lead compounds with high antibacterial activity, a series of new derivatives were designed and synthesized by introducing a sulfonate or carboxylate moiety into the 1,3,4-oxadiazole structure. Antibacterial activity against two phytopathogens, Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac), was assayed in vitro. The preliminary results indicated that ten compounds including 4a-1-4a-4 and 4a-11-4a-16 had good antibacterial activity against Xoo, with EC50 values ranging from 50.1-112.5 µM, which was better than those of Bismerthiazol (253.5 µM) and Thiodiazole copper (467.4 µM). Meanwhile, 4a-1, 4a-2, 4a-3 and 4a-4 demonstrated good inhibitory effect against Xanthomonas axonopodis pv. citri with EC50 values around 95.8-155.2 µM which were better than those of bismerthiazol (274.3 µM) and thiodiazole copper (406.3 µM). In addition, in vivo protection activity of compound 4a-2 and 4a-3 against rice bacterial leaf blight was 68.6% and 62.3%, respectively, which were better than bismerthiazol (49.6%) and thiodiazole copper (42.2%). Curative activity of compound 4a-2 and 4a-3 against rice bacterial leaf blight was 62.3% and 56.0%, which were better than bismerthiazol (42.9%) and thiodiazole copper (36.1%). Through scanning electron microscopy (SEM) analysis, it was observed that compound 4a-2 caused the cell membrane of Xanthomonas oryzae pv. oryzae ruptured or deformed. The present results indicated novel derivatives of 5-phenyl sulfonate methyl 1,3,4-oxadiazole might be potential antibacterial agents. Full article
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8 pages, 1303 KiB  
Article
Formal [3+2] Cycloaddition Reactions of Electron-Rich Aryl Epoxides with Alkenes under Lewis Acid Catalysis Affording Tetrasubstituted Tetrahydrofurans
by Víctor E. Macías-Villamizar, Luís Cuca-Suárez, Santiago Rodríguez and Florenci V. González
Molecules 2020, 25(3), 692; https://doi.org/10.3390/molecules25030692 - 6 Feb 2020
Viewed by 3997
Abstract
We report on the regio- and stereoselective synthesis of tetrahydrofurans by reaction between epoxides and alkenes in the presence of a Lewis acid. This is an unprecedented formal [3+2] cycloaddition reaction between an epoxide and an alkene. The chemical reaction represents a very [...] Read more.
We report on the regio- and stereoselective synthesis of tetrahydrofurans by reaction between epoxides and alkenes in the presence of a Lewis acid. This is an unprecedented formal [3+2] cycloaddition reaction between an epoxide and an alkene. The chemical reaction represents a very concise synthesis of tetrahydrofurans from accessible starting compounds. Full article
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2019

Jump to: 2023, 2022, 2021, 2020, 2018, 2017, 2016, 2015

18 pages, 1428 KiB  
Article
A Suitable Functionalization of Nitroindazoles with Triazolyl and Pyrazolyl Moieties via Cycloaddition Reactions
by Mohammed Eddahmi, Nuno M. M. Moura, Latifa Bouissane, Ouafa Amiri, M. Amparo F. Faustino, José A. S. Cavaleiro, Ricardo F. Mendes, Filipe A. A. Paz, Maria G. P. M. S. Neves and El Mostapha Rakib
Molecules 2020, 25(1), 126; https://doi.org/10.3390/molecules25010126 - 28 Dec 2019
Cited by 3 | Viewed by 3277
Abstract
The alkylation of a series of nitroindazole derivatives with 1,2-dibromoethane afforded the corresponding N-(2-bromoethyl)- and N-vinyl-nitro-1H-indazoles. The Cu(I)-catalysed azide- alkyne 1,3-dipolar cycloaddition was selected to substitute the nitroindazole core with 1,4-disubstituted triazole units after converting one of the N [...] Read more.
The alkylation of a series of nitroindazole derivatives with 1,2-dibromoethane afforded the corresponding N-(2-bromoethyl)- and N-vinyl-nitro-1H-indazoles. The Cu(I)-catalysed azide- alkyne 1,3-dipolar cycloaddition was selected to substitute the nitroindazole core with 1,4-disubstituted triazole units after converting one of the N-(2-bromoethyl)nitroindazoles into the corresponding azide. The reactivity in 1,3-dipolar cycloaddition reactions with nitrile imines generated in situ from ethyl hydrazono-α-bromoglyoxylates was studied with nitroindazoles bearing a vinyl unit. The corresponding nitroindazole-pyrazoline derivatives were obtained in good to excellent yields. Full article
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17 pages, 813 KiB  
Article
Synthesis and Antimicrobial Activity of a New Series of Thiazolidine-2,4-diones Carboxamide and Amino Acid Derivatives
by Rakia Abd Alhameed, Zainab Almarhoon, Sarah I. Bukhari, Ayman El-Faham, Beatriz G. de la Torre and Fernando Albericio
Molecules 2020, 25(1), 105; https://doi.org/10.3390/molecules25010105 - 27 Dec 2019
Cited by 18 | Viewed by 3652
Abstract
Novel thiazolidine-2,4-dione carboxamide and amino acid derivatives were synthesized in excellent yield using OxymaPure/N,N′-diisopropylcarbodimide coupling methodology and were characterized by chromatographic and spectrometric methods, and elemental analysis. The antimicrobial and antifungal activity of these derivatives was evaluated against two Gram-positive bacteria [...] Read more.
Novel thiazolidine-2,4-dione carboxamide and amino acid derivatives were synthesized in excellent yield using OxymaPure/N,N′-diisopropylcarbodimide coupling methodology and were characterized by chromatographic and spectrometric methods, and elemental analysis. The antimicrobial and antifungal activity of these derivatives was evaluated against two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), two-Gram negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and one fungal isolate (Candida albicans). Interestingly, several samples demonstrated weak to moderate antibacterial activity against Gram-negative bacteria, as well as antifungal activity. However, only one compound namely, 2-(5-(3-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetic acid, showed antibacterial activity against Gram-positive bacteria, particularly S. aureus. Full article
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16 pages, 1650 KiB  
Article
Synthesis and Antimicrobial Activity of Some New Substituted Quinoxalines
by Mohamed A. El-Atawy, Ezzat A. Hamed, Mahjoba Alhadi and Alaa Z. Omar
Molecules 2019, 24(22), 4198; https://doi.org/10.3390/molecules24224198 - 19 Nov 2019
Cited by 25 | Viewed by 5122
Abstract
A number of new symmetrically and asymmetrically 2,3-disubstituted quinoxalines were synthesized through functionalization of 2,3-dichloroquinoxaline (2,3-DCQ) with a variety of sulfur and/or nitrogen nucleophiles. The structures of the obtained compounds were established based on their spectral data and elemental analysis. The antimicrobial activity [...] Read more.
A number of new symmetrically and asymmetrically 2,3-disubstituted quinoxalines were synthesized through functionalization of 2,3-dichloroquinoxaline (2,3-DCQ) with a variety of sulfur and/or nitrogen nucleophiles. The structures of the obtained compounds were established based on their spectral data and elemental analysis. The antimicrobial activity for the prepared compounds was investigated against four bacterial species and two fungal strains. The symmetrically disubstituted quinoxalines 2, 3, 4, and 5 displayed the most significant antibacterial activity, while compounds 6a, 6b, and the pentacyclic compound 10 showed considerable antifungal activity. Furthermore, compounds 3f, 6b showed broad antimicrobial spectrum against most of the tested strains. Full article
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21 pages, 4977 KiB  
Review
Pyrido[2,3-d]pyrimidin-7(8H)-ones: Synthesis and Biomedical Applications
by Guillem Jubete, Raimon Puig de la Bellacasa, Roger Estrada-Tejedor, Jordi Teixidó and José I. Borrell
Molecules 2019, 24(22), 4161; https://doi.org/10.3390/molecules24224161 - 16 Nov 2019
Cited by 25 | Viewed by 5947
Abstract
Pyrido[2,3-d]pyrimidines (1) are a type of privileged heterocyclic scaffolds capable of providing ligands for several receptors in the body. Among such structures, our group and others have been particularly interested in pyrido[2,3-d]pyrimidine-7(8H)-ones (2) [...] Read more.
Pyrido[2,3-d]pyrimidines (1) are a type of privileged heterocyclic scaffolds capable of providing ligands for several receptors in the body. Among such structures, our group and others have been particularly interested in pyrido[2,3-d]pyrimidine-7(8H)-ones (2) due to the similitude with nitrogen bases present in DNA and RNA. Currently there are more than 20,000 structures 2 described which correspond to around 2900 references (half of them being patents). Furthermore, the number of references containing compounds of general structure 2 have increased almost exponentially in the last 10 years. The present review covers the synthetic methods used for the synthesis of pyrido[2,3-d]pyrimidine-7(8H)-ones (2), both starting from a preformed pyrimidine ring or a pyridine ring, and the biomedical applications of such compounds. Full article
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12 pages, 1783 KiB  
Article
A Simple, Efficient, and Eco-Friendly Method for the Preparation of 3-Substituted-2,3-dihydroquinazolin-4(1H)-one Derivatives
by Zainab Almarhoon, Kholood A. Dahlous, Rakia Abd Alhameed, Hazem A. Ghabbour and Ayman El-Faham
Molecules 2019, 24(22), 4052; https://doi.org/10.3390/molecules24224052 - 9 Nov 2019
Cited by 3 | Viewed by 3799
Abstract
A simple, cost-effective method under environmentally benign conditions is a very important concept for the preparation of 2,3-dihydroquinazolin-4(1H)-one derivatives. The present work describes an efficient and eco-friendly protocol for the synthesis of 2-amino-N-(2-substituted-ethyl)benzamide and 3-substituted-2,3-dihydroquinazolin-4(1H)-one derivatives. The [...] Read more.
A simple, cost-effective method under environmentally benign conditions is a very important concept for the preparation of 2,3-dihydroquinazolin-4(1H)-one derivatives. The present work describes an efficient and eco-friendly protocol for the synthesis of 2-amino-N-(2-substituted-ethyl)benzamide and 3-substituted-2,3-dihydroquinazolin-4(1H)-one derivatives. The novel feature of this protocol is the use of 2-methyl tetrahydrofuran (2-MeTHF) as an eco-friendly alternative solvent to tetrahydrofuran (THF) in the first step. In the second step, methanol in the presence of potassium carbonate as a catalyst was used under conventional heating or microwave irradiation, which provided an eco-friendly method to afford the target products in excellent yields and purities. NMR (1H and 13C), elemental analysis, and LC-MS confirmed the structures of all compounds. X-ray crystallography further confirmed the structure of the intermediate 2-amino-N-(2-substituted-ethyl)benzamide 3a. The molecular structure of 3a was monoclinic crystal, with P21/c, a = 13.6879 (11) Å, b = 10.2118 (9) Å, c = 9.7884 (9) Å, β = 105.068 (7)°, V = 1321.2 (2) Å3, and Z = 4. Full article
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12 pages, 1483 KiB  
Article
One Pot and Metal-Free Approach to 3-(2-Hydroxybenzoyl)-1-aza-anthraquinones
by Jiaqi Yuan, Qian He, Shanshan Song, Xiaofei Zhang, Zehong Miao and Chunhao Yang
Molecules 2019, 24(16), 3017; https://doi.org/10.3390/molecules24163017 - 20 Aug 2019
Cited by 4 | Viewed by 3445
Abstract
Herein, a direct strategy to synthesize 3-(2-hydroxybenzoyl)-1-aza-anthraquinones with excellent efficiency, mild conditions, and benign functional group compatibility was reported. A variety of 3-formylchromone compounds were employed as compatible substrates and this protocol gave the 3-(2-hydroxybenzoyl)-1-aza-anthraquinone derivatives in good to excellent yields without inert [...] Read more.
Herein, a direct strategy to synthesize 3-(2-hydroxybenzoyl)-1-aza-anthraquinones with excellent efficiency, mild conditions, and benign functional group compatibility was reported. A variety of 3-formylchromone compounds were employed as compatible substrates and this protocol gave the 3-(2-hydroxybenzoyl)-1-aza-anthraquinone derivatives in good to excellent yields without inert gas and expensive transition metal catalysts. Some compounds displayed good anti-proliferative activities. Full article
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14 pages, 2044 KiB  
Article
Intramolecular Carbene C-H Insertion Reactions of 2-Diazo-2-sulfamoylacetamides
by Chuqiang Que, Peipei Huang, Zhanhui Yang, Ning Chen and Jiaxi Xu
Molecules 2019, 24(14), 2628; https://doi.org/10.3390/molecules24142628 - 19 Jul 2019
Cited by 2 | Viewed by 4687
Abstract
The intramolecular C-H insertions of carbenes derived from 2-diazo-2-sulfamoylacetamides were studied. 2-Diazo-2-sulfamoylacetamides were first prepared from chloroacetyl chloride and secondary amines through acylation followed by sequential treatments with sodium sulfite, phosphorus oxychloride, secondary amines, and 4-nitrobenzenesulfonyl azide. The results indicate that: (1) 2-diazo- [...] Read more.
The intramolecular C-H insertions of carbenes derived from 2-diazo-2-sulfamoylacetamides were studied. 2-Diazo-2-sulfamoylacetamides were first prepared from chloroacetyl chloride and secondary amines through acylation followed by sequential treatments with sodium sulfite, phosphorus oxychloride, secondary amines, and 4-nitrobenzenesulfonyl azide. The results indicate that: (1) 2-diazo-N,N-dimethyl-2-(N,N-diphenylsulfamoyl)acetamide can take the formal aromatic 1,5-C-H insertion in its N-phenylsulfonamide moiety to afford the corresponding 1,3-dihydrobenzo[c]isothiazole-3-carboxamide 2,2-dioxide derivative; (2) no aliphatic C-H insertions occur for 2-diazo-2-(N,N-dialkylsulfamoyl)acetamides; and (3) for 2-diazo-N-phenyl-2-(N-phenylsulfamoyl)acetamides, the formal aromatic 1,5-C-H insertion in the N-phenylacetamide moiety is favorable to afford the corresponding 3-sulfamoylindolin-2-one derivatives as sole or major products. The intramolecular competitive aromatic 1,5-C-H insertion reactions of 2-diazo-2-sulfamoylacetamides with aryl groups on both amide and sulfonamide groups reveal that the N-aryl substituents on acetamide are more active than those on sulfonamide. The chemoselectivity is controlled by electronic effect of the aryl group. Full article
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33 pages, 3134 KiB  
Article
Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds—Mechanistic Insights
by Salem El Kharrat, Philippe Laurent, Laurent Boiteau and Hubert Blancou
Molecules 2019, 24(12), 2328; https://doi.org/10.3390/molecules24122328 - 25 Jun 2019
Cited by 3 | Viewed by 4107
Abstract
We report a new one-pot synthesis of 2-trifluoromethylated/2-perfluoroalkylated N-aryl-substituted pyridiniums, 5,6,7,8-tetrahydroquinoliniums and 6,7,8,9-tetrahydro-5H-cyclohepta[b]-pyridinium compounds starting from an activated β-dicarbonyl analogue (here a perfluoro-alkylated gem-iodoacetoxy derivative), an aromatic amine and a (cyclic or acyclic) ketone. The key step of [...] Read more.
We report a new one-pot synthesis of 2-trifluoromethylated/2-perfluoroalkylated N-aryl-substituted pyridiniums, 5,6,7,8-tetrahydroquinoliniums and 6,7,8,9-tetrahydro-5H-cyclohepta[b]-pyridinium compounds starting from an activated β-dicarbonyl analogue (here a perfluoro-alkylated gem-iodoacetoxy derivative), an aromatic amine and a (cyclic or acyclic) ketone. The key step of this multicomponent reaction, involves the formation of a 3-perfluoroalkyl-N,N’-diaryl-1,5-diazapentadiene intermediate, various examples of which were isolated and characterized for the first time, together with investigation of their reactivity. We propose a mechanism involving a concurrent inverse electron demand Diels-Alder or Aza-Robinson cascade cyclisation, followed by a bis-de-anilino-elimination. Noteworthy, a meta-methoxy substituent on the aniline directs the reaction towards a 2-perfluoroalkyl-7-methoxyquinoline, resulting from the direct cyclization of the diazapentadiene intermediate, instead of pyridinium formation. This is the first evidence of synthesis of pyridinium derivatives from activated β-dicarbonyls, ketones, and an aromatic amine, the structures of which (both reactants and products) being analogous to species involved in biological systems, especially upon neurodegenerative diseases such as Parkinson’s. Beyond suggesting chemical/biochemical analogies, we thus hope to outline new research directions for understanding the mechanism of in vivo formation of pyridiniums, hence possible pharmaceutical strategies to better monitor, control or prevent it. Full article
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13 pages, 1349 KiB  
Article
Facile Assembling of Novel 2,3,6,7,9-pentaazabicyclo- [3.3.1]nona-3,7-diene Derivatives under Microwave and Ultrasound Platforms
by Hamad M. Al-Matar, Kamal M. Dawood, Wael M. Tohamy and Mona A. Shalaby
Molecules 2019, 24(6), 1110; https://doi.org/10.3390/molecules24061110 - 20 Mar 2019
Cited by 6 | Viewed by 2820
Abstract
Reactions of a series of 3-oxo-2-arylhydrazonopropanal derivatives with two molar ratio of ammonium acetate afforded a library of tetrasubstituted 2,3,6,7,9-pentaazabicyclo[3.3.1]nona- 3,7-diene derivatives in good to excellent isolated yields. The reaction was activated with triethylamine catalyst under three different heating modes: thermal, ultrasonic and [...] Read more.
Reactions of a series of 3-oxo-2-arylhydrazonopropanal derivatives with two molar ratio of ammonium acetate afforded a library of tetrasubstituted 2,3,6,7,9-pentaazabicyclo[3.3.1]nona- 3,7-diene derivatives in good to excellent isolated yields. The reaction was activated with triethylamine catalyst under three different heating modes: thermal, ultrasonic and microwave irradiating conditions in ethanol solvent. The structures of the isolated products were fully characterized by spectral and analytical data as well as X-ray single crystal of selected examples. Full article
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20 pages, 1545 KiB  
Article
Synthesis, In Vitro Antimicrobial and Cytotoxic Activities of Some New Pyrazolo[1,5-a]pyrimidine Derivatives
by Ahmed M. Fouda, Hebat-Allah S. Abbas, Eman H. Ahmed, Ali A. Shati, Mohammad Y. Alfaifi and Serag Eldin I. Elbehairi
Molecules 2019, 24(6), 1080; https://doi.org/10.3390/molecules24061080 - 19 Mar 2019
Cited by 44 | Viewed by 4387
Abstract
A new series of pyrazole 47 and pyrazolo[1,5-a]pyrimidine 813 were synthesized by using a simple, efficient procedure, and screened for their in-vitro antimicrobial and antitumor activities. Symmetrical and asymmetrical 3,6-diarylazo-2,5,7-triaminopyrazolo[1,5-a]pyrimidine were synthesized by the conventional [...] Read more.
A new series of pyrazole 47 and pyrazolo[1,5-a]pyrimidine 813 were synthesized by using a simple, efficient procedure, and screened for their in-vitro antimicrobial and antitumor activities. Symmetrical and asymmetrical 3,6-diarylazo-2,5,7-triaminopyrazolo[1,5-a]pyrimidine were synthesized by the conventional method and also subjected to microwave irradiation and under ultrasound conditions. The biological results revealed that most of the tested compounds proved to be active as antibacterial and antifungal agents. The antitumor activity of the synthesized compounds was evaluated against human cancer cell lines, MCF-7, HCT-116, and HepG-2, as compared with Doxorubicin as a control. Full article
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13 pages, 3049 KiB  
Article
Convenient Synthesis of 6,7,12,13-Tetrahydro-5H-Cyclohepta[2,1-b:3,4-b’]diindole Derivatives Mediated by Hypervalent Iodine (III) Reagent
by Lei Peng, Xiaofei Zhang and Chunhao Yang
Molecules 2019, 24(5), 960; https://doi.org/10.3390/molecules24050960 - 8 Mar 2019
Cited by 8 | Viewed by 3476
Abstract
Bisindolyl alkaloids represent a large family of natural and synthetic products that display various biological activities. Among the bisindole compounds, 6,7,12,13-tetrahydro-5H-cyclohepta[2,1-b:3,4-b’]diindoles have received little attention. Only two methods have been developed for the construction of the 6,7,12,13-tetrahydro-5 [...] Read more.
Bisindolyl alkaloids represent a large family of natural and synthetic products that display various biological activities. Among the bisindole compounds, 6,7,12,13-tetrahydro-5H-cyclohepta[2,1-b:3,4-b’]diindoles have received little attention. Only two methods have been developed for the construction of the 6,7,12,13-tetrahydro-5H-cyclohepta[2,1-b:3,4-b’]diindole scaffold thus far, including the classical Fischer indole synthesis conducted by reacting indole-fused cycloheptanone and hydrazines, and the condensation reaction to build the seven-membered ring. Here, we report for the first time a new route to synthesize 6,7,12,13-tetrahydro-5H-cyclohepta[2,1-b:3,4-b’]diindoles through intramolecular oxidative coupling of 1,3-di(1H-indol-3-yl)propanes in the presence of PIFA, DDQ and TMSCl with moderate to excellent yields. Full article
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15 pages, 2717 KiB  
Article
Facile Access to Fe(III)-Complexing Cyclic Hydroxamic Acids in a Three-Component Format
by Evgeny Chupakhin, Olga Bakulina, Dmitry Dar’in and Mikhail Krasavin
Molecules 2019, 24(5), 864; https://doi.org/10.3390/molecules24050864 - 28 Feb 2019
Cited by 7 | Viewed by 3506
Abstract
Cyclic hydroxamic acids can be viewed as effective binders of soluble iron and can therefore be useful moieties for employing in compounds to treat iron overload disease. Alternatively, they are analogs of bacterial siderophores (iron-scavenging metabolites) and can find utility in designing antibiotic [...] Read more.
Cyclic hydroxamic acids can be viewed as effective binders of soluble iron and can therefore be useful moieties for employing in compounds to treat iron overload disease. Alternatively, they are analogs of bacterial siderophores (iron-scavenging metabolites) and can find utility in designing antibiotic constructs for targeted delivery. An earlier described three-component variant of the Castagnoli—Cushman reaction of homophthalic acid (via in situ cyclodehydration to the respective anhydride) was extended to involve hydroxylamine in lieu of the amine component of the reaction. Using hydroxylamine acetate and O-benzylhydroxylamine was key to the success of this transformation due to greater solubility of the reagents in refluxing toluene (compared to hydrochloride salt). The developed protocol was found suitable for multigram-scale syntheses of N-hydroxy- and N-(benzyloxy)tetrahydroisoquinolonic acids. The cyclic hydroxamic acids synthesized in the newly developed format have been tested and shown to be efficient ligands for Fe3+, which makes them suitable candidates for the above-mentioned applications. Full article
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20 pages, 5334 KiB  
Article
Synthesis of 4-Alkyl-4H-1,2,4-triazole Derivatives by Suzuki Cross-Coupling Reactions and Their Luminescence Properties
by Monika Olesiejuk, Agnieszka Kudelko, Marcin Swiatkowski and Rafal Kruszynski
Molecules 2019, 24(3), 652; https://doi.org/10.3390/molecules24030652 - 12 Feb 2019
Cited by 8 | Viewed by 4104
Abstract
New derivatives of 4-alkyl-3,5-diaryl-4H-1,2,4-triazole were synthesized utilizing the Suzuki cross-coupling reaction. The presented methodology comprises of the preparation of bromine-containing 4-alkyl-4H-1,2,4-triazoles and their coupling with different commercially available boronic acids in the presence of ionic liquids or in conventional [...] Read more.
New derivatives of 4-alkyl-3,5-diaryl-4H-1,2,4-triazole were synthesized utilizing the Suzuki cross-coupling reaction. The presented methodology comprises of the preparation of bromine-containing 4-alkyl-4H-1,2,4-triazoles and their coupling with different commercially available boronic acids in the presence of ionic liquids or in conventional solvents. The obtained compounds were tested for their luminescence properties. Full article
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2018

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10 pages, 1033 KiB  
Article
HFIP-Promoted Bischler Indole Synthesis under Microwave Irradiation
by Guangkai Yao, Zhi-Xiang Zhang, Cheng-Bei Zhang, Han-Hong Xu and Ri-Yuan Tang
Molecules 2018, 23(12), 3317; https://doi.org/10.3390/molecules23123317 - 14 Dec 2018
Cited by 5 | Viewed by 4786
Abstract
1,1,1,3,3,3-Hexafluoropropan-2-ol (HFIP) was found to be effective for the Bischler indole synthesis under microwave irradiation in the absence of a metal catalyst. Under the catalysis of HFIP, a wide range of α-amino arylacetones were successfully transformed into indole derivatives with moderate to good [...] Read more.
1,1,1,3,3,3-Hexafluoropropan-2-ol (HFIP) was found to be effective for the Bischler indole synthesis under microwave irradiation in the absence of a metal catalyst. Under the catalysis of HFIP, a wide range of α-amino arylacetones were successfully transformed into indole derivatives with moderate to good yields. Full article
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16 pages, 1657 KiB  
Article
Synthesis, Antibacterial, and Anti HepG2 Cell Line Human Hepatocyte Carcinoma Activity of Some New Potentially Benzimidazole-5-(Aryldiazenyl)Thiazole Derivatives
by Mohamed E. Khalifa, Adil A. Gobouri, Fahad M. Kabli, Tarik A. Altalhi, Abdulraheem S. A. Almalki and Mahmoud A. Mohamed
Molecules 2018, 23(12), 3285; https://doi.org/10.3390/molecules23123285 - 11 Dec 2018
Cited by 18 | Viewed by 4105
Abstract
The paper describes the synthesis and biological evaluation of some new benzimidazole derivatives as potent clinical drugs that are useful in the treatment of some microbial infections and tumor inhibition. The starting compound 2-(bromomethyl)-1H-benzimidazole (1) was prepared, and hence [...] Read more.
The paper describes the synthesis and biological evaluation of some new benzimidazole derivatives as potent clinical drugs that are useful in the treatment of some microbial infections and tumor inhibition. The starting compound 2-(bromomethyl)-1H-benzimidazole (1) was prepared, and hence underwent interesting functionalization reactions to afford several series of benzimidazole-5-(aryldiazenyl)thiazole derivatives: 3ac, 7ac, and 8ac. The antibacterial activities of the synthesized compounds were evaluated by calculation of the inhibition zone diameter (mm) and the determination of minimum inhibitory concentration (µg/mL) against selected pathogenic bacteria Staphylococcus aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria).Noticeable efficiency was found based on in vitro screening for their antioxidant activity and cytotoxicity effect against the human liver cancer cell line (HepG2) and human hepatocyte carcinoma cells at relatively high concentrations. Full article
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9 pages, 770 KiB  
Article
Conversion of Medium-Sized Lactams to α-Vinyl or α-Acetylenyl Azacycles via N,O-Acetal TMS Ethers
by Minjun Kim, Jaebong Jang, Goyoung Choi, Sungkyun Chung, Changjin Lim, Joonseong Hur, Hyun Su Kim, Younghwa Na, Woo Sung Son, Young-Ger Suh, Jong-Wha Jung and Seok-Ho Kim
Molecules 2018, 23(11), 3023; https://doi.org/10.3390/molecules23113023 - 19 Nov 2018
Cited by 5 | Viewed by 3627
Abstract
α-Vinyl or α-acetylenyl azacycles were easily synthesized from 7- to 9-membered lactams and 6- to 9-membered lactams via N,O-acetal trimethylsilyl (TMS) ethers. Organocopper and organostannane reagents afforded reasonable yields for the respective N-acyliminium ion vinylation and acetylenylation intermediates generated [...] Read more.
α-Vinyl or α-acetylenyl azacycles were easily synthesized from 7- to 9-membered lactams and 6- to 9-membered lactams via N,O-acetal trimethylsilyl (TMS) ethers. Organocopper and organostannane reagents afforded reasonable yields for the respective N-acyliminium ion vinylation and acetylenylation intermediates generated from N,O-acetal TMS ethers in the presence of a Lewis acid. Full article
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13 pages, 1551 KiB  
Article
Eco-Friendly Synthesis, Characterization and Biological Evaluation of Some Novel Pyrazolines Containing Thiazole Moiety as Potential Anticancer and Antimicrobial Agents
by Mastoura M. Edrees, Sraa Abu- Melha, Amirah M. Saad, Nabila A. Kheder, Sobhi M. Gomha and Zeinab A. Muhammad
Molecules 2018, 23(11), 2970; https://doi.org/10.3390/molecules23112970 - 14 Nov 2018
Cited by 36 | Viewed by 3748
Abstract
The one-pot synthesis of a series of pyrazoline derivatives containing the bioactive thiazole ring has been performed through a 1,3-dipolar cycloaddition reaction of N-thiocarbamoylpyrazoline and different hydrazonoyl halides or α-haloketones in the presence of DABCO (1,4-diazabicyclo[2.2.2] octane) as an eco-friendly catalyst using [...] Read more.
The one-pot synthesis of a series of pyrazoline derivatives containing the bioactive thiazole ring has been performed through a 1,3-dipolar cycloaddition reaction of N-thiocarbamoylpyrazoline and different hydrazonoyl halides or α-haloketones in the presence of DABCO (1,4-diazabicyclo[2.2.2] octane) as an eco-friendly catalyst using the solvent-drop grinding method. The structure of the synthesized compounds was elucidated using elemental and spectroscopic analyses (IR, NMR, and Mass). The activity of these compounds against human hepatocellular carcinoma cell line (HepG2) was tested and the results showed that the pyrazoline 11f, which has a fluorine substituent, is the most active. The antimicrobial activities of the newly synthesized compounds were determined against two fungi and four bacterial strains, and the results indicated that some of the newly synthesized pyrazolines are more potent than the standard drugs against test organisms. Full article
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22 pages, 6119 KiB  
Article
From Quinoxaline, Pyrido[2,3-b]pyrazine and Pyrido[3,4-b]pyrazine to Pyrazino-Fused Carbazoles and Carbolines
by Frédéric Lassagne, Timothy Langlais, Elsa Caytan, Emmanuelle Limanton, Ludovic Paquin, Manon Boullard, Coline Courtel, Idriss Curbet, Clément Gédéon, Julien Lebreton, Laurent Picot, Valérie Thiéry, Mohamed Souab, Blandine Baratte, Sandrine Ruchaud, Stéphane Bach, Thierry Roisnel and Florence Mongin
Molecules 2018, 23(11), 2961; https://doi.org/10.3390/molecules23112961 - 13 Nov 2018
Cited by 5 | Viewed by 5211
Abstract
2,3-Diphenylated quinoxaline, pyrido[2,3-b]pyrazine and 8-bromopyrido[3,4-b]pyrazine were halogenated in deprotometalation-trapping reactions using mixed 2,2,6,6-tetramethyl piperidino-based lithium-zinc combinations in tetrahydrofuran. The 2,3-diphenylated 5-iodo- quinoxaline, 8-iodopyrido[2,3-b]pyrazine and 8-bromo-7-iodopyrido[3,4-b]pyrazine thus obtained were subjected to palladium-catalyzed couplings with arylboronic acids [...] Read more.
2,3-Diphenylated quinoxaline, pyrido[2,3-b]pyrazine and 8-bromopyrido[3,4-b]pyrazine were halogenated in deprotometalation-trapping reactions using mixed 2,2,6,6-tetramethyl piperidino-based lithium-zinc combinations in tetrahydrofuran. The 2,3-diphenylated 5-iodo- quinoxaline, 8-iodopyrido[2,3-b]pyrazine and 8-bromo-7-iodopyrido[3,4-b]pyrazine thus obtained were subjected to palladium-catalyzed couplings with arylboronic acids or anilines, and possible subsequent cyclizations to afford the corresponding pyrazino[2,3-a]carbazole, pyrazino[2′,3′:5,6] pyrido[4,3-b]indole and pyrazino[2′,3′:4,5]pyrido[2,3-d]indole, respectively. 8-Iodopyrido[2,3-b] pyrazine was subjected either to a copper-catalyzed C-N bond formation with azoles, or to direct substitution to introduce alkylamino, benzylamino, hydrazine and aryloxy groups at the 8 position. The 8-hydrazino product was converted into aryl hydrazones. Most of the compounds were evaluated for their biological properties (antiproliferative activity in A2058 melanoma cells and disease-relevant kinase inhibition). Full article
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16 pages, 3608 KiB  
Article
Quinazolin-4(3H)-ones and 5,6-Dihydropyrimidin-4(3H)-ones from β-Aminoamides and Orthoesters
by Joshua T. Gavin, Joel K. Annor-Gyamfi and Richard A. Bunce
Molecules 2018, 23(11), 2925; https://doi.org/10.3390/molecules23112925 - 9 Nov 2018
Cited by 15 | Viewed by 4308
Abstract
Quinazolin-4(3H)-ones have been prepared in one step from 2-aminobenzamides and orthoesters in the presence of acetic acid. Simple 2-aminobenzamides were easily converted to the heterocycles by refluxing in absolute ethanol with 1.5 equivalents of the orthoester and 2 equivalents of acetic [...] Read more.
Quinazolin-4(3H)-ones have been prepared in one step from 2-aminobenzamides and orthoesters in the presence of acetic acid. Simple 2-aminobenzamides were easily converted to the heterocycles by refluxing in absolute ethanol with 1.5 equivalents of the orthoester and 2 equivalents of acetic acid for 12–24 h. Ring-substituted and hindered 2-aminobenzamides as well as cases incorporating an additional basic nitrogen required pressure tube conditions with 3 equivalents each of the orthoester and acetic acid in ethanol at 110 °C for 12–72 h. The reaction was tolerant towards functionality on the benzamide and a range of structures was accessible. Workup involved removal of the solvent under vacuum and either recrystallization from ethanol or trituration with ether-pentane. Several 5,6-dihydropyrimidin-4(3H)-ones were also prepared from 3-amino-2,2-dimethylpropionamide. All products were characterized by melting point, FT-IR, 1H-NMR, 13C-NMR, and HRMS. Full article
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15 pages, 4884 KiB  
Article
Regioselective Synthesis of New 2,4-(Het)aryl-3H-pyrido[1′,2′:1,5]pyrazolo[4,3-d]pyrimidines Involving Palladium-Catalyzed Cross-Coupling Reactions
by Abdelaziz Ejjoummany, Rabia Belaroussi, Ahmed El Hakmaoui, Mohamed Akssira, Gérald Guillaumet, Frédéric Buron and Sylvain Routier
Molecules 2018, 23(11), 2740; https://doi.org/10.3390/molecules23112740 - 23 Oct 2018
Cited by 6 | Viewed by 3068
Abstract
The design of some novel di-(het)arylated-3H-pyrido[1′,2′:1,5]pyrazolo[4,3-d]pyrimidine derivatives is reported. The series was developed from 1-aminopyridinium iodide, which afforded the key intermediate bearing two thiomethyl and amide functions, each of them useful for palladium catalyzed cross coupling reactions by alkyl [...] Read more.
The design of some novel di-(het)arylated-3H-pyrido[1′,2′:1,5]pyrazolo[4,3-d]pyrimidine derivatives is reported. The series was developed from 1-aminopyridinium iodide, which afforded the key intermediate bearing two thiomethyl and amide functions, each of them useful for palladium catalyzed cross coupling reactions by alkyl sulfur release and C-O activation, respectively. The two regioselective and successive cross-coupling reactions were first carried out in C-4 by in situ C-O activation and next in C-2 by a methylsulfur release. Process optimization furnished conditions leading to products in high yields. The scope and limitations of the methodologies were evaluated and the final compounds characterized. Full article
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19 pages, 26755 KiB  
Review
Synthesis of Multi-Substituted Pyrrole Derivatives Through [3+2] Cycloaddition with Tosylmethyl Isocyanides (TosMICs) and Electron-Deficient Compounds
by Zhengning Ma, Zicheng Ma and Dawei Zhang
Molecules 2018, 23(10), 2666; https://doi.org/10.3390/molecules23102666 - 17 Oct 2018
Cited by 48 | Viewed by 14538
Abstract
Pyrrole and its polysubstituted derivatives are important five-membered heterocyclic compounds, which exist alone or as a core framework in many pharmaceutical and natural product structures, some of which have good biological activities. The Van Leusen [3+2] cycloaddition reaction based on tosylmethyl isocyanides (TosMICs) [...] Read more.
Pyrrole and its polysubstituted derivatives are important five-membered heterocyclic compounds, which exist alone or as a core framework in many pharmaceutical and natural product structures, some of which have good biological activities. The Van Leusen [3+2] cycloaddition reaction based on tosylmethyl isocyanides (TosMICs) and electron-deficient compounds as a substrate, which has been continuously developed due to its advantages such as operationally simple, easily available starting materials, and broadly range of substrates, is one of the most convenient methods to synthetize pyrrole heterocycles. In this review, we discuss the different types of two carbon synthons in the Van Leusen pyrrole reaction and give a summary of the progress of these synthesis methods in the past two decades. Full article
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14 pages, 5283 KiB  
Article
Synthesis, Spectroscopic Characterization, and In Vitro Antibacterial Evaluation of Novel Functionalized Sulfamidocarbonyloxyphosphonates
by Abdeslem Bouzina, Khaoula Bechlem, Hajira Berredjem, Billel Belhani, Imène Becheker, Jacques Lebreton, Marc Le Borgne, Zouhair Bouaziz, Christelle Marminon and Malika Berredjem
Molecules 2018, 23(7), 1682; https://doi.org/10.3390/molecules23071682 - 10 Jul 2018
Cited by 13 | Viewed by 4353
Abstract
Several new sulfamidocarbonyloxyphosphonates were prepared in two steps, namely carbamoylation and sulfamoylation, by using chlorosulfonyl isocyanate (CSI), α-hydroxyphosphonates, and various amino derivatives and related (primary or secondary amines, β-amino esters, and oxazolidin-2-ones). All structures were confirmed by 1H, 13C, and 31 [...] Read more.
Several new sulfamidocarbonyloxyphosphonates were prepared in two steps, namely carbamoylation and sulfamoylation, by using chlorosulfonyl isocyanate (CSI), α-hydroxyphosphonates, and various amino derivatives and related (primary or secondary amines, β-amino esters, and oxazolidin-2-ones). All structures were confirmed by 1H, 13C, and 31P NMR spectroscopy, IR spectroscopy, and mass spectroscopy, as well as elemental analysis. Eight compounds were evaluated for their in vitro antibacterial activity against four reference bacteria including Gram-positive Staphylococcus aureus (ATCC 25923), and Gram-negative Escherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 700603), Pseudomonas aeruginosa (ATCC 27853), in addition to three clinical strains of each studied bacterial species. Compounds 1a7a and 1b showed significant antibacterial activity compared to sulfamethoxazole/trimethoprim, the reference drug used in this study. Full article
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3 pages, 175 KiB  
Correction
Correction: El-kalyoubi, S.; et al. Novel 2-Thioxanthine and Dipyrimidopyridine Derivatives: Synthesis and Antimicrobial Activity. Molecules, 2015, 20, 19263–19276
by Samar El-kalyoubi, Fatmah Agili and Shaker Youssif
Molecules 2018, 23(7), 1592; https://doi.org/10.3390/molecules23071592 - 29 Jun 2018
Viewed by 2721
Abstract
The authors wish to make the following changes to their paper [1].[...] Full article
11 pages, 3978 KiB  
Article
Synthesis of 8-Fluoro-3,4-dihydroisoquinoline and Its Transformation to 1,8-Disubstituted Tetrahydroisoquinolines
by Csilla Hargitai, Tamás Nagy, Judit Halász, Gyula Simig and Balázs Volk
Molecules 2018, 23(6), 1280; https://doi.org/10.3390/molecules23061280 - 26 May 2018
Cited by 3 | Viewed by 4282
Abstract
A simple procedure for the synthesis of 8-fluoro-3,4-dihydroisoquinoline is described below, based on a directed ortho-lithiation reaction. This key intermediate was then applied in various transformations. Fluorine–amine exchange afforded the corresponding 8-amino-3,4-dihydroisoquinolines, suitable starting compounds for the synthesis of 1-substituted 8-amino-tetrahydroisoquinolines. On [...] Read more.
A simple procedure for the synthesis of 8-fluoro-3,4-dihydroisoquinoline is described below, based on a directed ortho-lithiation reaction. This key intermediate was then applied in various transformations. Fluorine–amine exchange afforded the corresponding 8-amino-3,4-dihydroisoquinolines, suitable starting compounds for the synthesis of 1-substituted 8-amino-tetrahydroisoquinolines. On the other hand, reduction and alkylation reactions of 8-fluoro-3,4-dihydroisoquinoline led to novel 1,2,3,4-tetrahydroisoquinoline derivatives that can be used as building blocks in the synthesis of potential central nervous system drug candidates. Full article
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17 pages, 3418 KiB  
Article
Synthesis and Pharmacological Studies of Unprecedented Fused Pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b][1,3,4]thiadiazine Derivatives
by Rania S. Ali and Hosam A. Saad
Molecules 2018, 23(5), 1024; https://doi.org/10.3390/molecules23051024 - 27 Apr 2018
Cited by 5 | Viewed by 4094
Abstract
A novel fused system with three or four fused rings—pyridazino[3′,4′:5,6][1,2,4]triazino[4,3-b][1,2,4,5]tetrazine and pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b]pyrimido[4,5-e][1,3,4]thiadiazine was obtained from the starting materials 4(6H)-amino-3-hydrazino-7-(2-thienyl)pyridazino[3,4-e][1,2,4]-triazine 2 and 9-amino-3-(2-thienyl)-2H,8H-pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b][1,3,4]thiadiazine-8-carbonitrile 12. Each of the [...] Read more.
A novel fused system with three or four fused rings—pyridazino[3′,4′:5,6][1,2,4]triazino[4,3-b][1,2,4,5]tetrazine and pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b]pyrimido[4,5-e][1,3,4]thiadiazine was obtained from the starting materials 4(6H)-amino-3-hydrazino-7-(2-thienyl)pyridazino[3,4-e][1,2,4]-triazine 2 and 9-amino-3-(2-thienyl)-2H,8H-pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b][1,3,4]thiadiazine-8-carbonitrile 12. Each of the starting compounds was subjected to a number of cyclization reactions to obtain a series of new heterocyclic fused systems, 310 and 1323, via bifunctional reagents. Some of the synthesized compounds were screened against three cell lines including HepG2, HCT-116 and MCF-7 to discover their anticancer activity. The synthesized compounds were characterized depending on their elemental analyses and spectral data. Full article
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24 pages, 4066 KiB  
Article
Synthesis of Some Novel Fused Pyrimido[4″,5″:5′,6′]-[1,2,4]triazino[3′,4′:3,4] [1,2,4]triazino[5,6-b]indoles with Expected Anticancer Activity
by Rania S. Ali and Hosam A. Saad
Molecules 2018, 23(3), 693; https://doi.org/10.3390/molecules23030693 - 19 Mar 2018
Cited by 11 | Viewed by 4768
Abstract
Our current goal is the synthesis of polyheterocyclic compounds starting from 3-amino-[1,2,4]triazino[5,6-b]indole 1 and studying their anticancer activity to determine whether increasing of the size of the molecules increases the anticancer activity or not. 1-Amino[1,2,4]triazino[3′,4′:3,4]-[1,2,4]triazino[5,6-b]indole-2-carbonitrile (4) was [...] Read more.
Our current goal is the synthesis of polyheterocyclic compounds starting from 3-amino-[1,2,4]triazino[5,6-b]indole 1 and studying their anticancer activity to determine whether increasing of the size of the molecules increases the anticancer activity or not. 1-Amino[1,2,4]triazino[3′,4′:3,4]-[1,2,4]triazino[5,6-b]indole-2-carbonitrile (4) was prepared by the diazotization of 3-amino[1,2,4]-triazino[5,6-b]indole 1 followed by coupling with malononitrile in basic medium then cyclization under reflux to get 4. Also, new fused pyrimido[4″,5″:5′,6′