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
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.
Other Information
Published in: Journal of Organometallic Chemistry
License: http://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.1016/j.jorganchem.2025.123526
Funding
Open Access funding provided by the Qatar National Library.
History
Language
- English
Publisher
ElsevierPublication Year
- 2025
License statement
This Item is licensed under the Creative Commons Attribution 4.0 International License.Institution affiliated with
- Hamad Medical Corporation
- Qatar University
- Qatar University Health - QU
- College of Health Sciences - QU HEALTH
- College of Pharmacy - QU HEALTH
- College of Arts and Sciences - QU