Other Quinolines

The reaction follows the same course when one of the alkoxy groups in the starting material is replaced by alkyl. Thus, condensation of aniline (23-4) with EMME 

Antunalarial activity also predominates in a quinohne that bears a diaminoalkyl side chain at a rather different position from the agents noted in the previous section. Thus, Mannich condensation of the hydroxyquinoline (25-1) with formaldehyde and Ai,Ai-diethylpropylenediamine affords clamoxyquin (25-2) [29]. 

The quinoline nucleus sometimes serves as a surrogate for aromatic moieties this is illustrated by two NSAlDs that are closely related to the anthranUic acid fenac  

A somewhat different approach is used for the preparation of the analogue that contains a trifluoromethyl group. The scheme involves first the conversion of ort/zo-trifluoromethyl aniline (27-1) to a quinolol. The compound is thus condensed with EMME and cyclized thermally (27-2). That intermediate is then saponified the resulting acid is decarboxylated and finally converted to the 4-chloroquinoline (27-3) by reaction with phosphorus oxychloride. The displacement of chlorine with methyl anthranilate (27-4) then affords the coupled intermediate (27-5). An ester interchange of that product with glycerol leads to the glyceryl ester. There is thus obtained the NSAID flocatfenine (27-6) [31]. 

Similar considerations apply to leukotriene antagonists quinoline rings provide a role comparable to the benzopyran in the antagonist ablukast (11-7), discussed earlier in this chapter. Reaction of the product (28-1) from side chain chlorination 

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This mixture is known as Quinoline Yellow A [8003-22-3] (Cl 47000) and is most widely used with polyester fibers (109). Upon sulfonation, the water-soluble Quinoline Yellow S or Acid Yellow 3 [8004-92-0] (Cl 47005) is obtained. This dye is used with wool and its aluminum salt as a pigment. Foron Yellow SE-3GL (Cl Disperse Yellow 64) is the 3-hydroxy-4-bromo derivative. Several other quinoline dyes are commercially available and find apphcations as biological stains and analytical reagents (110). 

With quinoline and palladium-on-carbon the yields and conversions with different batches of catalyst were found to vary very widely but this matter has not been studied in detail, and similar data are still lacking for other quinolines. 

Most of the reactions with quinolines and degassed Raney nickels have been carried out at the atmospheric boiling point (above 230 C), a condition which is known to favor the formation of by-products. With quinoline and 4-methylquinoline (lepidine), however, the yields of the 2,2 -biquinolines were increased three to four times by heating in vacuo at 150° C, and it seems probable that other quinolines will behave similarly. Table II also shows that the yields of 2,2 -biquino-lines obtained under comparable conditions vary with the position of the methyl group in a fashion reminiscent of the trends observed with the pyridines (Table I). This similarity extends to the behavior of the two 2-methyl substituted quinolines studied, which undergo loss of the 2-methyl group to some extent and form traces of 2,2 -biquinolines. 

Walash et al. [10] determined primaquine and other quinoline drugs in bulk and in pharmaceuticals by a titrimetric method. The method is based on reaction with l,3-dibromo-5,5-dimethylhydantoin or TV-bromosuccinimide as the titrant. Primaquine was determined either by usual titration or by potentiometric titration with the brominating agents. The recovery was approximately 100%. The method was simple, precise, and accurate. 

Zheng and Sun [67] used a thin-layer chromatographic method for the analysis of primaquine and other quinoline derivatives. The drug and other compounds were chromatographed on silica gel GF254 plate, with methanol aqueous 25 28% ammonia (200 3) and chloroform dichloromethane diethylamine (4 3 1), as mobile phases. Spots were located under ultraviolet radiation. The detection limit was 12 pg/mL. Total separation could be achieved by the use of two plates and the respective mobile phase. 

Other quinoline A-oxide derivatives have been examined. A 1,3-oxazepine is the major product of irradiation of 2-cyanoquinoline A-oxide whereas lactam formation predominates on irradiation of 4-methylquinoline N-oxide in aqueous ethanol.60 Lactam formation has been shown to be influenced by an external magnetic field and on this basis it has been proposed that the first step in this transformation is the formation of an excited radical-ion pair.61 1,3-Oxazepines undergo further reaction on prolonged irradiation. The synthesis of 4-substituted indoles, for example, has been accomplished in this way by irradiation of 5-substituted quinoline A-oxides.62... 

This mixture is known as Quinoline Yellow A and is most widely used with polyester fibers. Several other quinoline dyes are commercially available and find applications as pigments, biological stains, and analytical reagents. 

F. Eden, A historical trip quinine and other quinoline alkaloids. Part 2. elucidation of the stereochemistry of quinoline alkaloids , Pharm. Zt., 1999, 28, 11-20 [in German],... 

Quinoline forms part of the structure of quinine, the malaria remedy found in cinchona bark and known since the time of the Incas. The quinoline in quinine has a 6-MeO substituent and a side chain attached to C4. In discussing the synthesis of quinolines, we will be particularly interested in this pattern. This is because the search for anti-malarial compounds continues and other quinolines with similar structures are among the available anti-malarial drugs. 

An important use of the traditional Skraup synthesis is to make 6-methoxy-8-nitroquinoline from an aromatic amine with only one free ortho position, glycerol, the usual concentrated sulfuric acid, and the oxidant arsenic pentoxide. Though the reported procedure uses 588 grams of As2Os, which might disconcert many chemists, it works well and the product can be turned into other quinolines by reduction of the nitro group, diazotization, and nucleophilic substitution (Chapter 23). 

Anodic oxidation of quinoline at a platinum anode in 75% sulfuric acid yields quinolinic acid (77%) [269] other quinolines bearing substituents in the hetero ring in the 3-position may do similarly, whereas some 2- and 4-substituted derivatives form tar [261]. 

Despite the emergence of drug-resistant strains of the parasite Plasmodium falciparum, the substituted 6-chloro-4-aminoquinoline, which is formally a 3-chloroaniline derivative, known as resochin, or chloroquine (130), and other quinolines, are still widely... 

Table 6.5 Highly enantioselective hydrogenations of other quinolines.

Oxidative aminations are possible at other quinoline and isoquinoline positions, even on the benzene ring, providing a nitro group is present to promote the nucleophilic addition ... 

Chou, A. C., and Fitch, C. D. (1993). Control of heme polymerase by chloroquine and other quinoline derivatives. Biochem. Biophys. Res. Commun. 195, 422 427. 

Loria, P., Miller, S., Foley, M., and Tilley, L. (1999). Inhibition of the peroxidative degradation of haem as the basis of action of chloroquine and other quinoline antimalarials. Biochem. ]. 339(Pt 2), 363-370. 

It was found among other quinolines and quinoxalines by Baltes and Knoch (1993) after roasting tryptophan with D-glucose or D-xylose. 

The mechanism of action of mefloquine is unknown but may be similar to that of chloroquine. Certain isolates of P. falciparum exhibit resistance to mefloquine via unknown mechanisms. Chloroquine-resistant alleles of the crt gene actually confer increased sensitivity to mefloquine and some other quinolines. Amplification of the pfmdrl gene is associated with resistance to mefloquine and quinine. 

One of the most interesting features of this type of ligands is that they present a binding cleft. In the conformational analysis of the 0s04(DHQD)2PHAL system, Norrby et al. observed that despite the large number of conformations a priori possible for this system, only a few variations of this U-shape conformation were found [39]. This U-shape conformation is formed by one quinoline in one side, the heterocyclic spacer at the bottom, and the OSO4 unit and sometimes the other quinoline at the other side (see Fig. 3). 

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