Quinolone analogues 10: Synthesis of antimalarial quinolones having pyridyl moiety in N1‐side chain

Abstract

in Wiley InterScience (www.interscience.wiley.com).Novel 4-quinolone-3-carboxylates 6,7 and 4-quinolone-3-carboxylic acids 8-11 were synthesized from 4-hydroxyquinoline-3-carboxylates. Ethyl 1-[1-ethoxycarbonyl-2-(4-pyridyl)vinyl]-6-fluoro-4-oxoquinoline-3-carboxylate 7a was found to show antimalarial activity from the screening data.

Quinolone Analogues 15: Synthesis and Antimalarial Activity of 4‐Phenyl‐1‐(1‐triazolylmethyl‐4‐quinolon‐3‐ylcarbonyl)semicarbazide and Related Compounds

“…The reaction of the 4‐quinolone‐3‐carboxylate ( 9 ) with hydrazine hydrate gave the 1‐hydrazinocarbonylmethyl‐4‐quinolone‐3‐carboxylate ( 10 ), whose hydrolysis with potassium hydroxide afforded the 1‐hydrazinocarbonylmethyl‐4‐quinolone‐3‐carboxylic acid ( 11 ) (Scheme ). The reaction of compound 11 with triethyl orthoacetate provided the 1‐[(1‐ethoxyethylidene)hydrazinocarbonylmethyl]‐4‐quinolone‐3‐carboxylic acid ( 12 ), whose reaction with hydrazine hydrate in the presence of 1,8‐diazabicyclo[5.4.0]‐7‐undecene furnished the 1‐(4‐amino‐1,2,4‐triazol‐3‐ylmethyl)‐4‐quinolone‐3‐carboxylic acid ( 13 ).…”

“…The in vitro antimalarial activity to chloroquine‐resistant P . falciparum (Gambia Cl D‐3 strain, ATCC 50037) was studied for new compounds according to a method described in previous articles . The 4‐phenyl‐1‐(1‐triazolylmethyl‐4‐quinolon‐3‐ylcarbonyl)(thio)semicarbazides 6a and 6b represented the antimalarial activity in concentration of 3.89 and 3.91 μM (IC 50 ), respectively, wherein the IC 50 of chloroquine as a reference was 0.22 μM.…”

“…In previous articles, we also reported the synthesis of the antimalarial 1‐(pyridin‐4‐ylalkenyl)‐4‐quinolone‐3‐carboxylate ( 1 ) , 1‐methyl‐4‐quinolone‐3‐[ N 2 ‐(pyridin‐2‐ylmethylene)]carbohydrazides ( 2 ) , and 1‐aryl‐3‐(4‐quinolon‐2‐yl)ureas ( 3 ) (Chart ). The 4‐quinolone ring and urea moiety of the 1‐aryl‐3‐(4‐quinolon‐2‐yl)ureas ( 3 ) were requisite for the antimalarial activity to Plasmodium falciparum , because the 1‐aryl‐3‐(4‐methoxyquinolin‐2‐yl)ureas ( 4 ) showed no antimalarial activity to P .…”

Quinolone Analogs 14: Synthesis of Antimalarial 1‐Aryl‐3‐(4‐quinolon‐2‐yl)ureas and Related Compounds

“…The in vitro antimalarial activity to chloroquine‐resistant P. falciparum (Gambia Cl D‐3, ATCC‐50037) was investigated for novel compounds 5 and 9 , 10 , 11 , 12 , 13 according to a method described in the previous papers . The screening data are shown in Table , wherein the IC 50 values are expressed in micromolar (μM) concentration.…”

“…Recently, we also reported the synthesis of the antimalarial 1‐(pyridin‐4‐ylalkenyl)‐4‐quinolone‐3‐carboxylate 3 and 1‐methyl‐4‐quinolone‐3‐[ N 2 ‐(pyridin‐2‐ylmethylene)]carbohydrazides 4 (Chart ) in the course of the study on structural modification of ordinary antibacterial new quinolones, which were also known as the antimalarial agent [IC 50 (below 10 µg/mL in ciprofloxacin)] . In continuation of the previous works, we synthesized 1‐aryl‐3‐(4‐quinolon‐2‐yl)ureas 5 in the present investigation, and some of compounds 5 were found to exhibit antimalarial activity better than compounds 3 and 4 , which would be due to the presence of urea moiety in compound 5 .…”