Evaluation of Quinazolin-2,4-Dione Derivatives as Promising Antibacterial Agents: Synthesis, In Vitro, In Silico ADMET and Molecular Docking Approaches DOI Creative Commons
Aboubakr H. Abdelmonsef, Mohamed El‐Naggar,

Amal O. A. Ibrahim

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(23), P. 5529 - 5529

Published: Nov. 22, 2024

A series of new quinazolin-2,4-dione derivatives incorporating amide/eight-membered nitrogen-heterocycles 2a–c, in addition, acylthiourea/amide/dithiolan-4-one and/or phenylthiazolidin-4-one 3a–d and 4a–d. The starting compound 1 was prepared by reaction 4-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-benzoyl chloride with ammonium thiocyanate cyanoacetic acid hydrazide. strong electrophiles, namely, o-aminophenol, o-amino thiophenol, o-phenylene diamine, resulted corresponding eight-membered 2a–d. Compounds 4a–d were synthesized good-to-excellent yield through a one-pot multi-component (MCR) carbon disulfide phenyl isocyanate under mild alkaline conditions, followed ethyl chloroacetate, iodide, methyl concentrated HCl, respectively. obtained products physicochemically characterized melting points, elemental analysis, spectroscopic techniques, such as FT-IR, 1H-NMR, 13C-NMR, MS. antibacterial efficacy the eleven molecules examined vitro against two Gram-positive bacterial strains (Staphylococcus aureus Staphylococcus haemolyticus). Furthermore, Computer-Aided Drug Design (CADD) performed on derivatives, standard drug (Methotrexate), reported target enzymes (S. S. haemolyticus) to explain their binding mode actions. Notably, our findings highlight compounds 2b 2c showing both best activity docking scores targets. Finally, according ADMET predictions, possessed acceptable pharmacokinetics properties drug-likeness properties.

Language: Английский

Unveiling the Synthesis of Indole-Fused Eight-Membered Aza-Heterocycles via FeCl3–Catalyzed Radical C–N Coupling and Photophysical Studies DOI
Sakshi Singh, Maitreya Maity, Shantanu Pal

et al.

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

A novel strategy toward construction of indole-fused eight-membered heterocyclic rings through a radical pathway has been reported. Our approach involves tandem cyclization via FeCl3-catalyzed cross-dehydrogenative double C–N bond formation using DDQ as an oxidant under mild condition. An EPR experiment and time course 1H NMR study confirm that the addition triggers pyrazole N-radical, which contributes to eight-member framework with good yield. The structural diversity synthetic utility have explored, along photophysical properties synthesized compounds.

Language: Английский

Citations

0
Palladium(0)-Catalyzed Regioselective Three-Component Cross-Coupling via C–H Activation: Synthesis of Eight-Membered Azacycles DOI

Qiongqiong Zhu,

Xiang Zuo,

Cang Cheng

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

A Pd(0)-catalyzed three-component cross-coupling reaction involving o-bromobenzylamines, aryl iodides, and alkynes was developed through C–H activation. This exhibits excellent regioselectivity, selectively forming a C(vinyl)–C(aryl) bond. The process yields eight-membered azacycles as the products, providing straightforward access to such compounds using simple substrates.

Language: Английский

Citations

0
Synthesis of 8-membered trifluoromethyl benzoxazocines via a Pd-catalyzed ring-expansion reaction of trifluoromethyl benzoxazinones with 2-methylidenetrimethylene carbonate and mechanistic investigations DOI
Bo Yang, Pengfei Sun, Xue Ma

et al.

Organic Chemistry Frontiers, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

A Pd-catalyzed ring-expansion reaction of trifluoromethyl benzoxazinones with 2-methylidenetrimethylene carbonate to access 8-membered benzoxazocines is reported.

Language: Английский

Citations

0
Ring opening of donor-acceptor-type cyclopropene unveils electrophilic ketene with vinylogous [4 C + n] periselective cyclization mode DOI Creative Commons
Jianhong Huang, Jiahang Li, Songlin Liu

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 29, 2025

Since its advent 120 years ago, the [2+n] coupling cyclization of ketene has been prevalently used for synthesis N- and O-heterocycles. In contrast, vinylogous version, i.e., use alkenyl as 4 C synthon, remain elusive. We report herein that in rare SN1-type ring-opening electron-deficient cyclopropene, initially formed sp2-carbocation-containing zwitterionic intermediate undergoes facile 1,4-alkoxy migration to generate a functionalized ketene. This electrophilic not only allows challenging N-nucleophiles be engaged conventional reactions (n = 1 ~ 3), also unveiled [4+n] mode, exemplified by [4 + 1] formal 4] construct pyrrolidinone azocine frameworks. The protocol offers unified entry distinct class lactam scaffolds exhibit anti-cancer potential, constituent key natural product scaffold display interesting 1e- 2e- reactivities. work reveals broader synthetic potential SN1 type cyclopropene "dehydro"-donor-acceptor cyclopropane (DDAC) substrate, could have ramifications chemistry, N-heterocyclic chemistry related medicinal research, well donor-acceptor system chemistry.

Language: Английский

Citations

0
Lewis Acid-Catalyzed Domino Inverse Electron-Demand Diels–Alder/Thermal Ring Expansion Reaction for the Synthesis of Arene-Annulated Eight-Membered Nitrogen Heterocycles DOI Creative Commons

Michel Große,

Christopher M. Leonhardt, P. Campbell

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

A domino inverse electron-demand Diels-Alder reaction/thermal ring expansion sequence was developed to enable the one-step synthesis of arene-annulated eight-membered nitrogen heterocycles from readily available aromatic 1,2-diazines. boron-based, bidentate Lewis acid catalyst facilitates initial cycloaddition Boc-protected 2-azetine with various electron-poor and electron-rich phthalazines. The subsequent electrocyclic furnishes azocines fused differently substituted aromatics, a structural motif that holds vast potential for further derivatization.

Language: Английский

Citations

0
Visible Light-Induced Cascade Phosphorylation/Cyclization to Access Phosphorus-Containing Diazocinocarbazoles DOI
Yifan Yin, Fei Liu, Miao Tian

et al.

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 16, 2025

Herein, we developed a novel radical cascade phosphorylation/cyclization strategy to access phosphorus-containing diazocine-fused carbazoles in moderate good yields, offering expanded opportunities for the exploration of biologically active molecules. This method features metal-free photochemical tandem, mild conditions, broad substrate scopes, and scale-up ability. Mechanistic experiments implied that this photocatalyzed reaction was realized by sequence EnT/SET/SET/radical addition/cyclization/SET/deprotonation processes.

Language: Английский

Citations

0
Expedient synthesis of 8-membered azasultams: A combined synthetic, DFT, and in vitro study DOI Creative Commons
Heorhii V. Posternak,

Olena D. Semoshkina,

Vasyl Y. Hys

et al.

Tetrahedron Chem, Journal Year: 2024, Volume and Issue: 11, P. 100085 - 100085

Published: July 17, 2024

Language: Английский

Citations

2
Sc(OTf)3-Catalyzed Precise Construction of Medium-Sized [4.2.1]-Oxabridged Scaffolds DOI

Dong-Sheng Ji,

Chenxing Zhou,

Xudong Wang

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 18, 2024

In this study, the readily available and inexpensive Sc(OTf)

Language: Английский

Citations

2
Palladium/Phosphine Complex Catalyzed [4＋4] Annulations of Morita-Baylis-Hillman Carbonates and 1-Azadienes DOI
Bo Zhu, Yang Yang, Qiang Liu

et al.

Chinese Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 44(12), P. 3761 - 3761

Published: Jan. 1, 2024

Language: Английский

Citations

1
Evaluation of Quinazolin-2,4-Dione Derivatives as Promising Antibacterial Agents: Synthesis, In Vitro, In Silico ADMET and Molecular Docking Approaches DOI Creative Commons
Aboubakr H. Abdelmonsef, Mohamed El‐Naggar,

Amal O. A. Ibrahim

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(23), P. 5529 - 5529

Published: Nov. 22, 2024

A series of new quinazolin-2,4-dione derivatives incorporating amide/eight-membered nitrogen-heterocycles 2a–c, in addition, acylthiourea/amide/dithiolan-4-one and/or phenylthiazolidin-4-one 3a–d and 4a–d. The starting compound 1 was prepared by reaction 4-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-benzoyl chloride with ammonium thiocyanate cyanoacetic acid hydrazide. strong electrophiles, namely, o-aminophenol, o-amino thiophenol, o-phenylene diamine, resulted corresponding eight-membered 2a–d. Compounds 4a–d were synthesized good-to-excellent yield through a one-pot multi-component (MCR) carbon disulfide phenyl isocyanate under mild alkaline conditions, followed ethyl chloroacetate, iodide, methyl concentrated HCl, respectively. obtained products physicochemically characterized melting points, elemental analysis, spectroscopic techniques, such as FT-IR, 1H-NMR, 13C-NMR, MS. antibacterial efficacy the eleven molecules examined vitro against two Gram-positive bacterial strains (Staphylococcus aureus Staphylococcus haemolyticus). Furthermore, Computer-Aided Drug Design (CADD) performed on derivatives, standard drug (Methotrexate), reported target enzymes (S. S. haemolyticus) to explain their binding mode actions. Notably, our findings highlight compounds 2b 2c showing both best activity docking scores targets. Finally, according ADMET predictions, possessed acceptable pharmacokinetics properties drug-likeness properties.

Language: Английский

Citations

0