Polycyclic N-Heterocyclic Compounds. Part 64: Synthesis of 5-Amino-1,2,6,7-tetrahydrobenzo[f]furo[2,3-c]isoquinolines and Related Compounds. Evaluation of Their Bronchodilator Activity and Effects on Lipoprotein Lipase mRNA Expression

Abstract

Reaction of 1-(3-cyanopropoxy)-3,4-dihydronaphthalene-2-carbonitriles with potassium tert-butoxide gave 5-amino-1,2,6,7-tetrahydrobenzo[f]furo[2,3-c]isoquinolines via a Truce–Smiles rearrangement. The 5-amino group was transformed to the bromo derivatives which were allowed to react with aliphatic cyclic amines to produce amino derivatives. In contrast, a combination of imidazole and NaH gave a dihydrofuran ring cleaved product, the structure of which was confirmed by X-ray crystallographic analysis. Effects of the newly synthesized compounds on carbamylcholine chloride-induced contractions of trachea and lipoprotein lipase mRNA expression were also evaluated and found one promising bronchodilator.