Synthesis of novel coumarin derivatives bearing heterocyclic substituents for chemoprophylactic evaluation

A series of coumarin derivatives bearing heterocyclic substituents was synthesized. Bromination of the key compound 8-acetyl-7-hydroxy-4-methylcoumarin [I] under varied conditions gave the brominated derivatives II, III and IV, Conversions of III by several cyclocondensations gave the corresponding thiazole V, quinoxaline VI, quinoxalinone VIII and furanone IX derivatives. Also, methylation and cyclocondensation of the methylene-active acetyl groups of II with several aldehydes gave the corresponding pyridone various amines gave the corresponding amino side chains. Some of these newly synthesized products were studied for their chemoprophylatic effect on Schistosoma mansoni infected mice. Compound Xc a showed moderate effect

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 chemoprophylactic effect of novel coumarin derivatives

A series of coumarin derivatives carrying different biologically active side chains and heterocyclic substituents were synthesized from 8-acetyl-4-methyl-7-hydroxycoumarin. Among these side chains are alkylamino, semicarbazono- and N[4]-substituted thiosemicarbazonoethyl, I-hydrazonoethyl and substituted I-hydroximinoethyl groups, while heterocyclic substituents were derived from pyran, oxadiazole, thiadiazole and thiazolidinone rings. Also, some derivatives of pyrano [2,3-h]chromen-9-carbaldehyde were synthesized. Some of these new products were studied for their chemoprophylactic effect in Schistosoma mansoni infected mice

Synthesis of some new coumarin derivatives incorporated to heterocyclie aromatic rings

3-bromo-4-methyl-7-coumarinyloxy acetic acid hydrazide was condensed with some aromatic aldehydes to give Schiff's bases 5 a-e which cyclized to thiazolidine derivatives 6a-e. Also, 7-O-[N-[succinimido] acetamido]-and 7-O-[[2-oxy-3-indolinylidene] acetic acid hydrazido]-3-bromo-4-methyl coumarins [3] and [4] were prepared. 7-O-[N-[sulfa drug] carbonyl methoxy]-3-bromo-4-methylcoumarin derivatives 10a-f were prepared via the formation of the acid chloride 9. Some of the new coumarin derivatives showed satisfactory results as molluscicidal activity against Biomphalaria alexandrina snails

Synthesis of some coumarin derivatives of possible biological activity

A series of bromocoumarins incorporated with aromatic derivatives via amino and ether linkages were synthesized. Also, hydrazocoumarin incorporated with thiosemicarbazides were prepared. Azole ring systems as 1,3,4-thiadiazole and 1,2,4-triazole were synthesized. Schiff bases which were cyclized with thioglycolic acid were prepared. Isatin moiety attached to hydrazocoumarin was prepared. The biological activity of some newly prepared compounds were carried out

Synthesis of novel uracil-5sulphonamide derivatives of possible biological activity

It has been reported that several uracil derivatives possess useful applications as anticancer agents. Also many uracil sulphonamides were found to possess inhibitory effect on the growth of Mycrnbacterium tuberculosis. On the other hand, several pyrazoles, 1, 2, 4-triazoles and pyridine derivatives were found to be bactericides, fungicides and anticancer agents. Based on these findings, it was of interest to prepare some novel uracil-5-sulphonamides linked to different heterocyclic systems namely 1, 2, 4-triazole5 5-pyrazolone and/or 3-pyridyl substituents starting with 5-[sulphonamido-p-carbethoxyphenyl] -uracil intermediate [III] in a trial to obtain compounds of possible biological activity