Regioselective domino C-C/C-O arylation of 1,2,3-triiodobenzenes and 1,3-diketones: Synthesis and in silico evaluation of 7-iodobenzo[b]furan as potential ALK inhibitors

被引:0
作者
Al-Zoubi, Raed M. [1 ,2 ,3 ]
Al-Jammal, Walid K. [3 ]
Shkoor, Mohanad [4 ]
Bani-Yaseen, Abdulilah D. [4 ]
Khan, Abbas [5 ,6 ]
Agouni, Abdelali [5 ]
Mcdonald, Robert [7 ]
机构
[1] Qatar Univ, Coll Hlth Sci, Dept Biomed Sci, QU Hlth, Doha 2713, Qatar
[2] Hamad Med Corp, Dept Surg, Surg Res Sect, Doha, Qatar
[3] Jordan Univ Sci & Technol, Dept Chem, POB 3030, Irbid 22110, Jordan
[4] Qatar Univ, Dept Chem & Earth Sci, POB 2713, Doha, Qatar
[5] Qatar Univ, Coll Pharm, Dept Pharmaceut Sci, QU Hlth, POB 2713, Doha, Qatar
[6] Sunway Univ, Jalan Univ, Sch Med & Life Sci, Dept Biomed Sci, Selangor 47500, Malaysia
[7] Univ Alberta, Gunning Lemieux Chem Ctr, Dept Chem, Edmonton, AB T6G2G2, Canada
关键词
Benzofuran; Iodination; Arylation; C-C coupling; C-O coupling; Substituent effect; Regioselectivity; SINGLE-CRYSTALLINE TRANSISTORS; METAL-IODINE EXCHANGE; 2,3-DISUBSTITUTED BENZOFURANS; CATALYZED SYNTHESIS; ACID-DERIVATIVES; FACILE SYNTHESIS; ONE-POT; X-RAY; EFFICIENT; PERFORMANCE;
D O I
10.1016/j.jorganchem.2025.123526
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
We report a simple, direct, and regioselective protocol for the synthesis of 2,3-disubstituted 7-iodobenzo[b]furans via domino double C-C/C-O arylations of 1,2,3-triiodobenzene and 1,3-dicarbonyl compounds. Remarkably, the C-arylation occurred exclusively at the terminal positions, which are the most reactive and least sterically hindered. The O-arylation reactions were selectively performed with the more reactive carbonyl group. This domino process demonstrated excellent substrate tolerance. Under optimized conditions, the reaction of electron-deficient 1,2,3-triiodoarenes with dicarbonyl compounds afforded the highest isolated yields. Furthermore, the designed novel compounds were screened against ALK, revealing that among the 17 tested, ALK-9p, ALK-9b, ALK-9n, and ALK-9m exhibited the best docking scores using the extra-precision docking method. Molecular simulations of these compounds with ALK confirmed their stable binding behavior, compact topology, and minimal residue flexibility. Finally, binding free energy calculations using MM/PBSA and MM/GBSA methods further validated the pharmacological potential of these shortlisted hits as ALK inhibitors. These results demand prompt experimental validation to determine the promising clinical applications of these compounds in the management of cancer
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页数:12
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