Phenothiazine analogue

Thioxanthenes differ structurally from phenothiazine in that the nitrogen atom of the central ring of the tricyclic system is replaced by carbon, which is joined to a side chain with a double bond. Their pharmacological action is similar to the corresponding phenothiazine analogues. They have the exact mechanism of action and an analogons effect on the CNS. Drugs of this series differ from one another by quantitative indexes. 

Describe how would you synthesize ethopropazine hydrochioride—a phenothiazine analogue from diphenylamine. 

Moricizine (Ethmozine) (Fig. 26.13) is a phenothiazine analogue that processes the same electrophysiological effects on the heart as those of Class 1C antiarrhythmics. Despite its short half-life after oral administration, its antiarrhythmio effects can persist for many hours, suggesting that some of its metabolites may be active. 

X = NO2) with triethyl phosphite or by heating the azide (229 X = N3) was not successful, but phenothiazine analogues were obtained by the Bamford-Stevens reaction with (229 X = CH=NNHTos). ... 

In the field of phenothiazine analogues, Grol has described the synthesis of some isomeric dithienothiazines and thienobenzothiazines by applying an Ullmann-type cyclization to the appropriate dithienyl and thienyl aryl sulphides. A more convenient route to the dithienothiazine ring system is illustrated by the direct sulphuration of the dithienylamide (87) with sulphur dichloride,... 

The synthesis of 2-hydroxy-3H-phenoxazinones from o-aminophenols and quinones has been successfully adapted to the preparation of the phenothiazine analogues, e.g. (138), by condensation of 2,5-dimethoxy-l,4-benzoquinones with SH-protected o-aminobenzenethiols (137), followed by... 

Chlorpromazine is technically described as a phenothiazine, as are thioridazine and fluphenazine. Together with their structural analogues the thioxanthenes (e.g., clopenthixol) and the butyrophenones (e.g., haloperidol), the phenothiazines comprise the three major families of typical neuroleptics. They were developed in the late 1950s and early 1960s (Table 11.3). All these drugs block dopamine receptors, principally the D2 subtypes, with an affinity that correlates highly (r = +0.90) with their clinical... 

Recently, several series of tetracyclic analogues related to tenidap, represented by (158) (X = S, O, or CH2 R = aryl), have been reported to display a better balance of 5-LO and CO inhibition [386]. However, these compounds may also be considered as modified phenothiazine, phenoxazines, and acridines, and the enhanced 5-LO inhibition may be more closely related to that of other phenothiazines such as (88). 

Neuroleptic activity profiles. The marked differences in action spectra of the phenothiazines, their derivatives and analogues, which may partially resemble those of butyrophenones, are important in determining therapeutic uses of neuroleptics. Relevant parameters include antipsychotic efficacy (symbolized by the arrow) the extent of sedation and the ability to induce ex-trapyramidal adverse effects. The latter depends on relative differences in antagonism towards dopamine and acetylcholine, respectively (p. 188). Thus, the butyrophenones carry an increased risk of adverse motor reactions because Lullmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and oonditlons of lloense. 

As structural analogues of the phenothiazines, thioxanthenes (e.g., chlorprothixene, flupentixol) possess a central nucleus in which the N atom is replaced by a carbon linked via a double bond to the side chain. Unlike the phenothiazines, they display an added thy-moleptk activity. 

It is known from electrochemical studies that fullerenes are easily reduced. Up to 6 electrons can be added reversibly [19], and, as mentioned earlier, the excited states are even more easily reduced. A large number of electron donors were investigated including aromatic and alkyl amines [29,43,79,119-140,152,161], ni-troxide radicals [57,117], suspensions of Ti02 [118], polyaromatic compounds, [19,127] organo-silicon compounds, [133,158] phenothiazine, [133] acridine [145,154], (3-carotene [141], tetrathiafulvalenes [146], tetraethoxyethene [147], phthalocyanines [148], porphyrines [151,153], NADH and analogues [150,154, 155], borates [156,159], and naphtoles [23] to name a few representative cases. 

Treatment of [RuCl(terpy)(bipy)]+ with CF3S03H under N2 gives [Ru(03SCF3)(terpy)(bipy)]+, which when treated with dry air at 110°C for 5h yields the Ru 1 analogue [Ru(03S-CF3)(terpy)(bipy)]2+.1256 Aquation of [Ru(03SCF3)(terpy)(bipy)]2+ occurs readily to give [Ru(terpy)(bipy)OH2]3+.1203,1204,1256 The luminescence and redox chemistry of [Ru(terpy)(bipy)L]2+ (L = OH2, phenothiazine, TV-methylphenothiazine, thianthrene) have been reported.1259... 

The phosphorescence of trivalent cations (as analogues of Ca ) is also widely used in binding studies. The photobinding of phenothiazine derivatives has been studied for different types of biological membranes. The specificity of binding is low, although general, and can be used to identify and localize membrane proteins. The influence of Ca " and phase behaviour in synaptosomal lipids have been examined by the steady-state fluorescence polarization of A fluorescent probe of the tumour promoter phorbol... 

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