Acridine derivatives

Quinacrine. Quinacrine (7), C23H2QCIN2O, is an acridine derivative. It is used in the form of the dihydrochloride dihydrate,... 

In future a third new group will be required, according to another preliminary statement published quite recently by a team of Australian chemists, Messrs. Hughes, Lahey, Price and Webb. They have isolated six alkaloids from three rutaceous species of that country, five of which have been definitely shown to be acridine derivatives. This appears to be the fiipst-fruits of a survey of the type referred to above, which is being carried out on the Australian flora under the auspices of the Council for Scientific and Industrial Research and several of the Australian Universities. ... 

The ring expansions of acridine derivatives to dibenz[/j, / ]azcpines (see Section 3.2.1.4.1.5.) are reversible in hot mineral acid.29 161-184 227 For example, 5-acetyl-52/-dibcnz[/j./]azcpine (1) in refluxing 48% hydrobromic acid furnishes 9-methylacridine (2).29... 

Harrison RJ et al. (1999) Human telomerase inhibition by substituted acridine derivatives. Bioorg Med Chem Lett 9(17) 2463-2468... 

The aromatic spacer group of the model receptors prevent the formation of intramolecular hydrogen bonds between the opposing carboxyls yet these functions are ideally positioned for intermolecular hydrogen bonds of the sort indicated in 32. The acridine derivatives do indeed form stoichiometric complexes with oxalic, malonic (and C-substituted malonic acids) as well as maleic and phthalic acids, Fumaric, succinic or glutaric acids did not form such complexes. Though protonation appears to be a necessary element in the recognition of these diacids, the receptor has more to... 

Acridine derivatives, such a proflavine (5) and acridine orange (6) (Scheme 3), are a second class of intercalative DNA guest molecules for which binding dynamics have been extensively studied. 

A-acetoxy-lV-/e//-butoxybenzamide, 55 /V-acyloxy- /V-alkoxyalky lam ides, 55 /V- acy I o x y- /V-a I k o x y u re as, 56 /V-chlorohydroxamic esters, 56 N, /V-dialkoxyamidcs, 56 Intercalative guest molecules, binding dynamics of DNA with, 186-201 acridine derivatives, 190-194 9-aminoacridine carboxamide derivatives, 194, 195... 

Acridine derivatives, such as acriflavine (1.31), can be regarded as relatives of the diphenylmethane class in which the two benzene nuclei are linked by nitrogen to form a pyridine ring. Their insignificance nowadays resembles that of their relatives, but they were formerly useful mainly as orange or yellow basic dyes [28]. 

Cyclic 1,3-diketones can also participate in this MCR. Thus, utilization of two equivalents of 1,3-cyclohexanedione or dimedone instead of (3-ketoesters led to hydrogenated acridine derivatives. However, when only one equivalent of cyclic 1,3-dicarbonyl is used in combination with one equivalent of (3-ketoester, unsym-metric 1,4-DHPs may be obtained (Scheme 3). For example, this reaction was applied to the synthesis of ZD0947, a potassium chaimel opener [20]. 

Hypersensitivity to tacrine or acridine derivatives patients previously treated with tacrine who developed treatment-associated jaundice a serum bilirubin greater than 3 mg/dL signs or symptoms of hypersensitivity (eg, rash or fever) in association with ALT elevations. 

Reaction of aldoximes with dimedone derivatives under microwave irradiation leads to partially hydrated acridine derivatives . Eused heterocyclic compounds containing partially hydrogenated pyridine and quinoUne rings were prepared by intramolecular cycloaddition reaction of 5-alkynyl oxime derivatives . (Z)-l,10a-Dihydropyrrolo[l,2-i>]... 

Chemical Class Cholinesterase inhibitor monoamine acridine derivative Clinical Pharmacology ... 

The synthesis of 2-hydroxycarbostyrils has recently been described (81S729). Patent literature also details their preparation, for example that of (97), and their use as antidepressants (69USP3452027). A somewhat similar acridine derivative (98) is a reported antiviral (79GEP2759468). 

This rearrangement, however, is complex and further studies show it to be dependent on temperature, solvent, pH and, most importantly, the absence or presence of oxygen. A similar overall mechanistic scheme operates for the acid-catalyzed rearrangement of A/-nitroso-5//-dibenz[6,/]azepine to acridine derivatives e.g. acridine-9-aldehyde) (74CRV101). 

To come to a water-soluble, ditopic receptor model, Lehn etal. attached JV6-[24] crown-8 with an acridine-derived DNA-intercalator, so combining the anion binding strength of the first (in protonated state) [67] with the n-stacking capacity of the latter. Indeed, increased binding of ATP by 46 was observed as compared with the unsubstituted azacrown [68]. Additionally, the multifunctional host 46 catalyzes the hydrolysis of ATP [69] with a higher selectivity over ADP as compared with the parent crown but with a somewhat reduced eflectiv-ity. The reaction intermediate was shown to be the Af-phosphorylated crown. 

The most frequently reported oxidation reaction of isatins is the oxidation with alkaline hydrogen peroxide to give anthranilic acids. This procedure has been both as a proof of structure of isatins and as a method of synthesis of anthranilic acids. The oxidation has been applied to alkyl 8"10 11 23 33>38-40>46 49>50>118halo n.18.35.36-38-40.47.10 .11 . 119,136,240 alkoxy,26,a8 39,47,75.io7,ii8,i36 trifluoromethyl,33,38,137 and nitro8,120,217 isatins. Use of N-substituted isatins led to N-substituted anthranilic acids.66,71,125,158,169,243 In the oxidation of 5-bromo-l-(y-carbethoxypropyl)-7-ethylisatin, 60 was isolated after treatment with ethanol and acid.11 Oxidation of isatin derivatives 61 led, after treatment with diazomethane, to the acridine derivatives 62.67 Application of this oxidation method to 7-hydroxyisatins gave rise to benzoxazo-lones (63).2,41... 

Quinoline and acridine derivatives, which are not very numerous and are mostly yellow, orange or red. 

B. Assemblies of Anthryl, Pyrenyl, Ethidium, and Acridine Derivatives... 

Fukuda, R. Takenaka, S. Takagi, M., (1990) Metal ion assisted DNA-intercalation of crown ether-linked acridine derivatives Chem. Commun. 1028-1030. 

The calculated [a]D for 1 (5R,11R) is -341.5 (aug-cc-pVDZ) and -319.8 (6-311 + +G(2s,2p) [the calculated [a]D(0) are -242.3 and -224.0, respectively]. The last value is in excellent agreement with the experimental result (91JOC485). Italian authors (03JOC5186) have tried unsuccessfully to use small basis sets with 1 only to have a moderate success with an acridine derivative similar to NIHMEW (Scheme 21) experimental [a]D = 4800 (04HCA279), calculated (6-31G ) [ ]D = 2384 (03JOC5186). 

In addition, the UV spectra have been explored more thoroughly. In two papers, Tatibouet and Demeunynck reported the study of acridine derivatives. First they noted that the UV-visible absorption of the acridine chromophore in 16a (NIH-MEW, Scheme 21) exhibits large variations as compared to the parent acridine (97BSF495). As was commented in Section IV.A.2, these authors recorded the UV-visible spectrum of (+)-16b in the presence of increasing concentrations of calf thymus DNA, experiments used to demonstrate that 16b interacts with DNA (99CC161). As reported in Section IV.A.4, the UV-visible titration of 38b with tetraamines confirmed the formation of 2 1 and 1 1 complexes (98CC11). 

In the case of terpyridine and acridine derivatives, the bis(methylamines) are the most convenient intermediates. Substituted 4/-phenyl-2,2/ 6/,2"-terpyridines were prepared by reacting (ii)-propenons and iV-[2-(pyrid-2 -yl)-2-o octln l p ridinium iodide with ammonium acetate in acetic acid or in methanol. The terminal pyridine moieties were oxidized with 3-chloroperbenzoic acid to iV, A" -dio idcs followed by modified Reisserty-Henze reaction to obtain 6,6"-dicarbonitriles. The bis(methylamines) were obtained by reduction of the 6,6"-dicarbonitriles withborane (scheme 8 (Mukkala et al., 1993)). 

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