5-nitro-2-furyl derivatives

Nitroheteroarenes continue to attract research activity. A series of 5-nitro-2-furyl derivatives were evaluated for in vivo efficacy against T cruzi [64] and an improved toxicity profile. Compound 65 showed a good efficacy profile in vivo and better acute toxicity profile when compared to nifurti-mox. A series of 5-nitroindazoles, represented by 66 (IC50 = 7.4 iM), were reported as having activity similar to nifurtimox (IC50 = 3.4 iM) in a growth inhibition assay [65]. 

Furyl)-3-(5-nitro-2-furyl)acrylamide (see AF-2) Fusarenon-X (see Toxins derived trom Fusarium graminearum,... 

Bromo-2-furyl)quinoxaIine and 3-(5-nitro-2-furyl)-2-quin-oxalinone, and numerous substituted derivatives, have been synthesized and found to be active antibacterials and antimicrobials.153 2-[2-(5-Nitro-2-furyl)vinyl]quinoxalines (147) have also been prepared, and some derivatives (6-nitro and 6-amino) were found to have high tuberculostatic activity.134... 

The nitration of l-methyl-2-(2-furyl)- and l-methyl-2-(2-thienyl)imidazoles in polyphosphoric acid was described [149, 150], At room temperature the nitro group enters at position 5 both of the furan and of the thiophene rings. Nitration of the furan derivative by 2 moles of nitric acid leads mainly to the dinitro derivative l-methyl-2-(5-nitro-2-furyl)-5-nitroimidazole [149], The introduction of a second nitro group into the thienyl derivative requires more rigorous conditions (80°C, 2 moles of nitric acid). Its position in the imidazole ring was not established [150],... 

In a boiling mixture of nitric (d 1.50) and concentrated sulfuric acids 2-chloroben-zimidazole gives 2-chloro-5,6-dinitrobenzimidazole in a 75-80% yield [67], In analogous conditions, benzimidazole and 2-alkyl substituted benzimidazoles are also transformed into 5,6-dinitro derivatives however, in this case simultaneous formation of 4,6-dinitro isomers, which can be separated by fractional crystallization, has been fixed [48, 68], 5(6)-Nitro-2-heterylbenzimidazoles (thiazolyl-4-, furyl-4-, and pyrrolyl-4-) having antihelminthic activity were obtained by nitration with sulfuric-nitric mixture on cooling [69],... 

Solvolyses data for 5-substituted 2-furylmethanol derivatives have been correlated.446 Results for arylation fit Hammett plots using a+ values provided that the aryl radical contains strongly polar substituents such as nitro or halogen.4461 Another correlation involves eliminations in 1 -(2-furyl)-ethyl acetate to give furyl alkenes.447 The furan ring itself has been assigned a a value.4-146... 

Other uses of reduced indoxazenes include the antibacterial and antiprotozoal activity of 3-(5-nitro-2-furyl)-3a,4,5,6,7,7a-hexahydro derivatives,127... 

The antibacterial action of several new nitrofurans in vitro against a number of organisms has been reported by Skagius . These data indicate that 5-(5-nitro-2-furyl)-2-amino-l,3,4-thiadiazole (NF-475, ASA-140, Ph/ 778, LXXI) and its formyl derivative LXXII) have been recommended for further study in the treatment of intestinal infections of various aetiology. 

The isopropyl and ethoxycarbonylmethyl derivatives of 3-(5-nitro-2-furyl) acrylamide proved to be effective in the treatment of Schistosoma japonicum °. After one to two weeks of therapy with a total dosage of 700 to 1,500 mg of one of the drugs, 50 per cent of all treated patients had negative stool specimens. The rate of worm elimination in animals (drug doses were not stated) was extremely high in mice 100 per cent, in rabbits 97 to 100 per cent, and in dogs 85 to 90 per cent . 

The valine-derived thiourea (236) has been shown to catalyse addition of (cyclic) )3-keto esters to RCH=CHN02 (R = aryl, 2-furyl, and PhCH2CH2) in toluene at -18 °C with <98 2 dr and <98% ee at 2mol% loading. Thiourea (131) at (g) 10mol% loading exhibited <94% ee in the addition of methoxycarbonyl succinimide to nitro alkenes, carried out in CH2CH2 at -20 °C.322 0... 

The first rec-assay survey on food additives was carried out in 1971 for synthetic dyes, and phloxine (Red Dye No. 104) was found to be positive. The mutagenicity of phloxine was then demonstrated in E. coli WP2 try. AF-2 [2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide], a nitrofuran food preservative, was rec-assayed and found to be a potent mutagen. This substance has been widely used in Japan, and the results initiated a continuing debate on the problem of toxicities due to chemical mutagens. Like other nitrofuran derivatives, AF-2 at first gave negative results with the Ames assay. Positive results appeared later using strains with R plasmid pKMlOl. 

The antischistosome activity of nitrofuran compounds was further investigated. Comparison of 3-(5-nitro-2-furyl)-substituted derivatives of propionic, acrylic and propiolic acids showed that a vinyl group is necessary for activity.1 5 in derivatives of 3-(5-nitro-2-furyl) acrylic acid, the 5-nitro group was required for activity.12 In a group of (5-nitro-2-furyl)-vinyl heterocycles containing a weakly basic N in a specific position, both the vinyl group and the N were essential for antischistosome activity.1 ... 

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