engleski

Novel tetracyclic imidazole derivatives: Synthesis, dynamic NMR study, and anti-inflammatory evaluation

A series of tetracyclic imidazole derivatives 9a–9v and 10a–10h are prepared by multistep route start- ing from the known tricyclic diketones 2a–2d. Intermediary dibenzooxepin[4, 5-d]imidazoles (3a, 3c) and dibenzothiepin[4, 5-d]imidazoles (3b, 3d) are N-protected to 4e, 4f and to the isomeric compounds 5a, 5b and 6a, 6b. The isomeric compounds 5 and 6 are separated. Compounds 4, 5, and 6 are formy- lated at C(2) to afford 7a–7j. In the last steps, aldehyde group is reduced, then alkylated to the two sets of isomeric x-dimethylaminoalkyl derivatives 9a–9v. N-deprotection of 9i–9v led to the compounds 10a–10h. Assignment of the syn/anti structure to 5a and 6a was supported by 1D selective ROESY NMR spectra, whereas conformational mobility for the selected representatives 8a and 8b is studied by and 16.2 kcal/mol, respectively. A series of derivatives 9 and 10 were tested in vitro for their anti- dynamic NMR. Activation energies (energy barriers for interconversion) are determined to be ?11.5 inflammatory activity.

tetracyclic imidazole derivative, synthesis, NMR

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