Synthesis and Reactions of Pyrido[2,1‐a]isoquinolin‐4‐yl Formimidate Derivatives and Antimicrobial Activities of Isolated Products

Abstract

Treatment of arylidene malononitriles 2A–C with 1‐cyanomethylisoquinoline 1 afforded 4‐amino‐2‐arylpyrido[2,1‐a]isoquinoline‐1,3‐dicarbonitrile derivatives 5A–C, which converted to formimidates 6A–C via reaction with triethylorthoformate. Treatment of the latter compounds with hydrazine hydrate gave the corresponding amino–imino compounds 7A–C, which underwent Dimroth rearrangement to afford 13‐aryl‐1‐hydrazinylpyrimido[5′,4′:5,6]pyrido[2,1‐a]isoquinoline‐12‐carbonitrile 8A–C. The latter reacted with aldehyde to give 9a–i. Oxidative cyclization of the latter compounds 9a–i gave [1,2,4]triazolo[4″,3″:1′,6′]‐pyrimido[5′,4′:5,6]pyrido[2,1‐a]isoquinolines 10a,d,g. Such compounds isomerized to the thermodynamically more stable isomers [1,2,4]triazolo[1″,5″:1′,6′]pyrimido[5′,4′:5,6]‐pyrido[2,1‐a]isoquinolines 11a,d,g. Antimicrobial activities for some compounds were studied.

Hantzsch‐like reaction of isoquinoline‐1‐acetonitrile in synthesis of 4H‐pyrido[2,1‐a]isoquinolines with antibacterial evaluation

“…Based on the mentioned beneficials of isoquinoline derivatives specially pyrido [2,1-a]isoquinolines in continuation to the previous work of our research group that focused on the synthesis of isoquinoline-containing compounds [21][22][23][24][25][26][27], we sythesized new 4H-pyrido[2,1-a]isoquinolines by reacting 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl) acetonitrile 1 with ethylacetate derivatives 2,6,7 and ethyl 3-aryl-2-cyanoacrylates 11a-f. Moreover, we evaluated the antibacterial activity of the synthesized compounds against gram-positive and gram-negative bacteria.…”

Synthesis and Prediction of the Ubiquinol‐cytochrome c Reductase Inhibitory Activity of 3,4‐Dihydroisoquinolines and 2‐Azaspiro[4.5]decanes (Spiropyrrolines)

“…Isoquinoline derivatives evince a wide range of biological activities. For example, partially hydrogenated isoquinoline derivatives can act as antagonists of dopamine receptors, exhibit antiproliferative, antitumor, anthelmintic, analgesic, antimicrobial, antibacterial, and other activities . In synthesis of 3,4‐dihydroisoquinolines and their derivatives, the most frequently used reactions are those of Bischler–Napieralsky, Pictet–Spengler, and Pomeranz–Fritsch .…”