Synthesis and anticoagulant and antiarrhythmic activity of oximes of isoquinolyl-1-glyoxylic acid derivatives

Abstract

As is known, isoquinoline derivatives possess antiarrhythmic and and anticoagulant properties [ 1 8]. Previously we have reported on these types of activity in 3,4-dihydroisoquinoline derivatives [9, 10]. The purpose of this work is to synthesize a series of oximes of 3,3-disubstituted 3,4-dihydroisoquinoline derivatives and study their antiarrhythmic and and anticoagulant activity. Aleksandrov et al. [11, 12] showed that oximes of this type can be obtained by treating monoand disubstituted derivatives of 1,3,3-trimethyl-3,4-dihydroisoquinoline with nitrous acid, whereby one of the substituents is eliminated in the form of alcohol. Since 1,3,3-trimethyl-3,4-dihydroisoquinoline derivatives containing carbonyl, carbamoyl, or ester groups can be formally considered as analogs of I]-dicarbonyl compounds, it was expected that these derivatives would readily interact with nitrous acid to form the corresponding nitroso compounds. These intermediate products can be subsequently rearranged to form the oximes of 3,3-dialkyl-3,4-dihydroisoquinolyl-l-glyoxylic acid derivatives and related compounds. Indeed, treatment of the solutions of the carbonyl-containing derivatives of 3,3-dialkyl-3,4-dihydroisoquinoline in 10% aqueous HCI with a sodium nitrite equivalent, followed by neutralization of the reaction mass, led to a high yield of the expected oximes with the characteristics listed in Table 1. It must be noted that, in contrast to what was reported in [12], we failed to isolate the intermediate nitroso compounds.