Synthesis of some new 4-[P-heterocyclo-substituted aniline] -2,7-dimethyl-l,8-naphthyridines of expected antimicrobial activity

The reaction of 4-chloro-2,7-dimethyl-l,8-naphthyridine [1] with benzocaine and/or aminophenol gives the corresponding ethyl naphthyridineaminobenzoate derivative 2a and/or p-hydroxy-anilinonaphthyridine derivative 2b depending upon the nature of the reactants used. The reaction of compound 2a with hydrazine hydrate gives the corresponding acid hydrazide 3 which was allowed to react with CS[2] at different conditions giving the oxadiazole 4 and / or the dithiocarbazate 5, and with a beta-diketone and a [3-dikctoester to give the corresponding pyrazole 9 and/or the pyrazolone 10. As well as, the reaction of the acid hydrazide 3 with different aromatic aldehydes afforded the Schiff bases 11a-d. which upon cyclization with thioglycolic acid afforded the thiazolidinones 12. On the other hand, the reaction of 1 with different amines, afforded 4-substituted 1,8-naphthyridines 13a-c, which gave the 2,7- distyrylnaphthyridines 14a-d upon reaction with different aromatic aldehydes. Moreover, reaction of 1 with p-hydroxy- acetophenone and/or p-aminophenol gave the corresponding 4-[p-acetylphenoxy] and/or 4-[p-aminophenoxy]-1,8-naphthyndine derivatives 15a and/or 15b, respectively. Reaction of 15a with different aldehydes afforded the chalcones 16a-d, 2-[lH] oxopyridines 17a-f, 2-[lH]iminopyndmes 19a,b, 2-[lH] thioxopyndincs 20a-c, while reaction of 15b with aromatic aldehydes gave the 1,8-naphthyridine-p-phenoxy Schiff bases 21a-c and other related compounds have been synthesized. Furthermore, some 1,8-naphthyridine Mannich bases 24a-d were produced by treatment of 2b with p-formaldchyde and secondary amines. In addition, reaction of 4 with ethanolic solution of paraformaldehyde and the appropriate secondary amine, afforded the corresponding 1,3,4-oxadiazole Mannich bases 25a-c. Some of the new compounds were evaluated for their antimicrobial activity

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]

Synthesis and in vitro anticancer evaluation of some new [tetrahydronaphthalen-2y1] nitrogen heterocycles

Condensation of 2-acetyltetralin I with two aromatic aldehydes afforded the respective chalcones 7a,b. When the reaction of 1 with aldehydes was conducted in presence of ethylcyanoacetate and/or malononitrile and ammonium acetate, it yielded tetrahydronaphthalenyl nicotinonitriles of types 3 and 4. Chalcones 7a,b yielded 2-pyrimidinones 8a,b, 2- thiopyrimidines 9a,b and pyrazoline derivatives 10a,b upon reaction with urea, thiourea and hydrazine, respectively. Reaction of compound 5 with different amines gave the corresponding anilino-derivatives. Compounds 3a, 9a, 10a, 5, and 6b were evaluated for their anticancer activity