Synthesis of pharmacologically active 1-amino-isoquinolines prepared via silver triflate-catalyzed cyclization of o-alkynylbenzaldoximes with isocyanates

Abstract

The synthesis of a series of 1-amino-isoquinolines prepared via electrophilic cyclization [3+2] cycloaddition/rearrangement reactions of o-alkynylbenzaldoxime 1 with isocyanates 2 in the presence of catalytic amount of AgOTf was demonstrated. The cyclized products were obtained in good yields under an air atmosphere. 1-Amino-isoquinoline derivatives 3a, 3b, 3j and 3t were screened in vitro for the antioxidant potential and efficacy to inhibit cerebral monoamine oxidase (MAO) activity. The antidepressant-like action of some 1-amino-isoquinolines was performed in the mouse forced swimming test (FST). The pharmacological screening of 1-amino-isoquinoline derivatives indicated that 3a, 3b, 3j and 3t were antioxidants and inhibited cerebral MAO-A and B activities at low concentrations. Although at different doses 3a, 3b, 3j and 3t were effective antidepressant-like drugs in the mouse FST. None of 1-amino-isoquinolines tested caused acute cerebral, hepatic or renal toxicity in mice.

Keywords: Antidepressant-like; Antioxidant; Cyclization reaction; Isoquinolines; Silver cycloaddition.