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ID: ALA1131354

Journal: Bioorg Med Chem Lett

Title: Synthesis of benzocycloalkane derivatives as new conformationally restricted ligands for melatonin receptors.

Authors: Kloubert S, Mathé-Allainmat M, Andrieux J, Sicsic S, Langlois M.

Abstract: Benzocycloalkane derivatives 1-4 were synthesized as new conformationally restricted melatoninergic ligands. They were prepared by the reaction of the ketones 5 with diethylcyanophosphonate and the reduction of the corresponding cyano compounds or by the Wittig reaction and Curtius degradation to obtain the amines 8. The 1-Cyanobenzocyclobutane derivative was obtained by the benzyne cyclisation reaction. The amines 8 were acylated with acetyl, propionyl or butyryl groups. The affinity of the compounds for chicken brain melatonin receptors was evaluated using 2-[125I]-iodomelatonin as the radioligand. The indanyl (2b,c), tetralin (3a-c) and benzocycloheptane (4c) derivatives were potent compounds with nanomolar affinity and an important enantioselectivity of the receptor was observed with the (+) enantiomers 2b and 3b.

CiteXplore: 9873728

DOI: 10.1016/s0960-894x(98)00601-5