Synthesis of new 2-[2-(dialkyl(diaryl)-phosphoryl)-2-methylpropyl]quinoline-4-carboxylic acids

Abstract

The quinoline nucleus is widely present in pharmacologically active compounds. Quinoline derivatives exhibit various types of biological effects, including antibacterial, 1-4 tuberculostatic, 5-7 antimalarial, 8 and antitumor activity. 9,10 It was also found that quinoline derivatives containing phosphonate or phosphine oxide fragments 11,12 possess antiinflammatory 13 and antiHIV activity. 14 Besides that, we previously showed that hydrazones of isoniazid and dimephosphone (antacid medication, dimethyl (2-methyl-4-oxopent-2-yl)phosphonate) 15 or its Р,С-analogs, dialkyl (2-methyl-4-oxopentyl)phosphine oxides, 16 are significantly less toxic compared to isoniazid, while maintaining its therapeutic effect. [17][18][19] We have recently found that phosphine oxides 1, 16 containing a methyl ketone fragment, are capable of interacting in the Pfitzinger reaction with isatin to yield new phosphorus-containing quinoline-4-carboxylic acids 2. 20,21 In this work, we report the synthesis of a range of new 4-quinolinecarboxylic acid derivatives containing a phosphine oxide fragment by using the Pfitzinger reactioninteraction of isatin with 2-methyl(4-oxopent-2-yl)dialkyl-(diphenyl)phosphine oxides (Scheme 1, Table 1). We also performed preliminary biological activity screening for the obtained compounds.The quinolinecarboxylic acids 2a-g were synthesized by refluxing equimolar amounts of isatin and oxoalkylphosphine oxides 1a-g in aqueous ethanolic medium. The optimum reaction duration according to TLC control was 18-24 h.A Pfitzinger reaction of isatin with 2-methyl-(4-oxopent-2-yl)dialkyl(diphenyl)phosphine oxides was used to synthesize new derivatives of 4-quinolinecarboxylic acids, containing a phosphine oxide fragment, and screening for antimicrobial activity was performed.