New antimicrobial 9-[p-heterocyclo-substituted anilino]-tetrahydroacridines

The chemistry of tetrahydroacridines is of continuous interest, as they are associated with pharmacological activities[1-9]. Some members of this class of compounds are used as memory-enhancing agents for treating Alzheimer disease [1, 2] acetylcholine esterase inhibitors[3-5], DNA-binding agents[6], antimicrobial agents[7] and as amoebicides[7-9]. The present work deals with the synthesis of a new series of 9-[p-[4-aryl- 3-cyano-2-iminopyridin-6-yl] anilino]-1, 2, 3, 4-tetrahydroacridines [3] and their 2-oxo-[or thioxo]-pyridinylanilino derivatives 4 and 5, besides other related products 7-12 to be evaluated against bacteria and fungi. Synthesis was achieved by allowing 9-chloro-1, 2, 3, 4-tetrahydroacridine [1][10] to react with p-aminoacetophenone to give the 9-[p-acetylanilino] derivative 2. The one pot reaction of 2 with malononitrile, ammonium acetate and the appropriate aromatic aldehyde afforded the corresponding 9-[p-[4-aryl-3-cyano-2-iminopyridin-6-yl]-anilino]-1, 2, 3, 4-tetrahydroacridines [3a-e], respectively [Route a]. Similarly, reaction of 2 with ethyl cyanoacetate, ammonium acetate and the appropriate aromatic aldehyde in n-butanol afforded the corresponding 9-[p-[4-aryl-3-cyano-2[1H]-oxo-pyridin-6-yl] anilino]-1, 2, 3, 4-tetrahydroacridines [4a-d], respectively. On the other hand, the reaction of an ethanolic mixture of 2 with substituted arylmethylene cyanothioacetanilides [5][11, 12] in the presence of ammonium acetate gave the corresponding 3-cyano-4-arylpyridin-2[1H]-thiones [6a-d], respectively [Route a]. Also reaction of 1 with ethyl-p-aminobenzoate gave the corresponding ethyl-p-[1, 2, 3, 4-tetra-hydroacridin-9-yl] aminobenzoate [7] which upon reaction with hydrazine hydrate afforded the corresponding acid hydrazide 8. [Route b]. In addition, acetylation of 2 was accomplished by heating it with ethyl acetate in the presence of sodium metal to give p-[[1, 2, 3, 4-tetrahydroacridin-9-yl]amino]acetylacetophenone [9]. Bromination of 2 afforded 9-[p-bromo-acetyl anilino]-1, 2, 3, 4-tetrahydroacridine [10] which upon reaction with thiourea gave the corresponding 9-[p-[2-aminothiazol-4-yl]aniline-1, 2, 3, 4-tetrahydroacridine [11] was hydrobromide salt, while reaction of 10 with malononitrile afforded p-[1, 2, 3, 4-tetrahydroacridin-9-yl]amino-benzoylmethyl malononitrile [12] [Route c]

Novel 5,6,7,8-Tetrahydronaphth-2-yl heterocycles of possible biological activity

2-cyclocondensation 2 underwent with different alpha-cyanocinnamonitriles to give the corresponding poly substituted pyran derivatives 3[a-d] which upon treatment with carbon disulphide gave the pyranopyrimidindithione derivatives 4[a-c]. Also, treatment of 2 with different aldehydes afforded the corresponding cinnamonitrile derivatives 5[a,b] which upon reaction with 3-methyl-1- phenylpyrazol-5-one gave the corresponding pyranopyrazole derivatives 6[a,b]. Moreover imidazo [2,3-b] thiazoles 8[a,c]; 1,2,3- thia- or 1,2,3- selena-diazoles 10[a,b]; thiazolidinones 16[a,b] and benzoxazin-4-one derivatives 18[a,b] derivatives were synthesized starting with 2-acetyltetralin. Compounds 3[c],11[b],12 were tested as antibilharzial agents and compounds 6[a],8[a] as antileukemia agents in experimental animals. Some of these compounds showed moderate activity

Synthesis, molecular modeling and anticancer activity of certain acridine derivatives

Eight series of new acridine derivatives of anticipated antitumor activity were synthesized. The first and second series belong to 9- anilinoacridines. The third series belongs to 9-anilinoacridine-4- ylmethylamino benzenesulfonamides. The fourth one composes of acridone methylamino benzenesulfonamides. The fifth and sixth series comprise of 9-anilinoacridine-4-acetamide derivatives. The seventh series is the derivatives of 9-oxo-9,10-dihydroacridine-4-acetamide. The last series includes 9-oxo-9,10-dihydroacridine-2-sulfonamides. Also, one known final compound has been synthesized following a new pathway. The rationale behind the synthesis of these compounds, their methods of synthesis as well as their antitumor activity, were discussed

Atomic absorption spectrophotometry for the determination of some antihypertensive agents

Atomic absorption spectrophotometric methods for the determination of oxprenolol hydrochloride, indapamide and captopril were developed. The methods were based on the determination of oxprenolol hydrochloride and indapamide via their chloride contents and captopril via its sulphur content. In case of oxprenolol hydrochloride, an excess of standard silver nitrate was added, the precipitated silver chloride was centrifuged and the silver contents of both the precipitate and the decanted solution were determined by atomic absorption spectrophotometry. In case of indapamide, oxygen flask combustion method was first carried out. Captopril was ashed using oxygen flask combustion method, followed by adding a known excess of barium chloride and the precipitated barium sulfate was centrifuged. The excess barium chloride in the decanted solution was determined by atomic absorption spectrophotometry

Synthesis of certain period [1,2-c] pyramid [5,4-e] pyrimidines of expected pharmacological interest

Five series of the titled nucleus were prepared. Enaminonitrile I reacted with oxalyl chloride and chloroacetyl chloride to afford the tricyclic compounds II and III, respectively. II reacted with various alcohols to give the corresponding ester, also III reacted with various amines to yield the corresponding compounds. The anti-inflammatory effect of some members showed significant results as compared with Diclofenac. Another derivatives were found to inhibit 50% of the histamine induced contraction of guinea pig ileum. It is worth mentioning that the animals treated with the test substances were more quiet and less aggressive than the control

Substituted nitrogen bridgehead heterocycles of potential smooth muscle relaxant and antihypertensive activities

Pyrrolo [1,2-c] pyrimidine derivatives I reacted with various acid chlorides to afford a number of 3-substituted pyrimido [5,4-e] pyrrolo [1,2-c] pyrimidines. The 3-chlorocarbonyl intermediate I-A reacted with different alcohols to give the corresponding esters. Moreover, 3-chloromethyl derivative I-B reacted with thiourea, alkoxides and sodium salts of aromatic acids to yield thiouronium salts, ethers and esters, respectively. Some members were tested as smooth muscle relaxant diuretic and hypotensive activities. It was shown that compound VII-a is the potent as hypotensive and diuretic agent. Also, it was noticed that, while all the test substances inhibit the uterine motility, VII-a stimulates the uterine motility in all stages

Synthesis of benzopyrono-1,4-oxazines as new tricyclic antidepressant agents

A number of benzopyrano [7,6-b], [7,8-b]- and [5,6-b]-1,4-oxazines was synthesized by elaboration of the oxazine ring on a performed substituted benzopyrone nucleus. Six of the final compounds as well as 2 of their precursors, o-acetamidobenzopyron-yloxyketones were found to have an antidepressant like profile in behavioral and calorigenic tests predictive of antidepressant efficacy

Synthesis of some novel heterocyclic compounds of potential antiallergic activity

Dicyanomethylidene 1a and its piperidine analogue 1b reacted with B-chloroethylisocyanate to afford unexpectedly the heterocycles: imidazo [1,2-c] pyrrolo [2,1-f] pryrimidine-10-carbonitrile and imidazo [1,2-c] pyrido [2,1-f] pyrimidine-11-carbonitrile hydrochlorides 3a and 3b respectively. Subsequent hydrolysis gave the corresponding carboxamides 4a,b and carboxylic acids 6a,b. The structures of the new nuclei have been confirmed by chemical and spectral means. Two compounds were subjected to pharmacological testing and have shown 50% inhibition of the histamine induced contraction of guinea pig ileum

Synthesis and effect of new tetrahdronaphthyl pyrazoline on carbohydrate metabolism in bilharzia snails

A series of 1-acetyl-5-aryl-3-[6-[1,2,3,4-tetrahydronaphthyl]]- delta2-pyrazolines [IIa-f] were synthesized by the reaction of the corresponding 1,2,3,4-tetrahydronaphthalene-chalcones [Ia-f] with hydrazine hydrate in boiling acetic acid. The effect of two of the new delta2-pyrazolines [IIa and IIb] on aerobic oxidation, glucose level, glycogen content and activity of transaminases in Biomphalaria alex and rina snails tissues were determined. The most pronounced effects of these compounds were on the activities of lactate oxidase and pyruvate reductase, while no effect of these compounds was detected on glucose, glycogen and transaminases when used at their LC50 concentration. The relationship between the metabolic effects of these compounds and their molluscicidal activities are discussed

Synthesis and antitumor activity of some N [p-substituted sulfamoylphenyl] Arcadian 4-carboxamides and N [p-substituted sulfamoylphenyl] -11-oxo-11 H pyrido [2, 1-b] quinazoline-6-carboxamides

Two series of N [p-substituted sulfamoylphenyl] acridone-4- carboxamides and N [p-substituted sulfamoylphenyl]-11-oxo-11-H-pyrido [2,1-b] quinazoline-6-carboxamides have been synthesized, representative compounds have been tested for antitumor activity

Synthesis and biological activity of some new 5-nitrothiazole derivatives

Synthesis of certain new 5-nitrothiazole derivatives as analogues of niridazole was described. Preliminary antischistosomal evaluation and the effect on the content of nucleic of compounds VI and VE in white mice liver were studied

Condensed pyrimidines

Treatment of enaminonitriles pyrrolo [1, 2-c] pyrimidine and pyrimido [1, 6-a] azepine with different arylaldehydes yielded either the tricyclic compounds pyrimido [5, 4-e] pyrrolo [1, 2-c] pyrimidine and pyrimido [4', 5': 4, 5] pyrimido [1, 2-a] azepine respectively or the uncyclized 3-benzylidene derivatives

Condensed pyrimidines XIII

Acylation of the enaminonitriles was carried out using halogenated acid chlorides yielding substituted alkyl halides. The chlorine atom in the chloroalkyl moiety was replaced by different amines or condensed with thiourea and the formed salts were hydrolized to give the thioalkyl compounds. Moreover, enaminonitriles were reacted with oxalyl chloride to afford the 3-chlorocarbonyl derivatives from which esters and amide were prepared. The 3-carboxylic acid derivatives were also prepared and subjected to decarboxylation. Compounds containing the pyrimidine ring represent an important group of heterocyclic compounds that draw attention for their biological activities

Synthesis of some new quinoline-mannich bases and other related products of possible antimicrobial activity

The synthesis of thirteen new quinoline-Mannich bases and 1,2,4- triazolo [4,3-a] quinolines was reported. These include four intermediates and nine final new compounds. The chemical structures of these compounds were confirmed by elemental and spectral analyses. Two representative compounds were tested for antimicrobial and antifungal activities. The results obtained indicated that the tested compounds possess a potent antimicrobial activity and lower antifungal properties

New 5-nitrothiazolyl heterocycles of possible schistosomicidal activity

Some new p-cinamoylanilinothiazoles and other 5-nitrothiazoles attached to pyrazoles, isoxazoles and/or pyrimidones were synthesized for the purpose of biological evaluation against Schistosoma mansoni in mice. Some of them showed marked activity

New tetrahydronaphthyl pyridones of possible analgesic activity

For possible analgesic activity, a series of 6-[6-tetrahydronaphthyl]-3-cyano-pyridin-2-ones [IIa-c] were synthesized by two different routes. All of the tested pyridones showed considerable analgesic properties on experimental animals corresponding to 1.4 times as acetyl salicylic acid using hot-plate method