Synthetic studies of Alkoxy isoindole-1 , 3-diones tetra-azabenzo [ f ] azulenes and their Antibacterial activity

3-Methylpyrazol-5-one 3 reacts with substituted benzaldehydes 4a-d in the presence of anhydrous sodium acetate to produce the corresponding 4arylidene-5-methyl-2,4-dihydro-pyrazol-3-ones 5a-d and the condensation of 5a-d with 2-bromoalkoxy-1H-isoindole-1, 3-(2H)-diones 2a-c furnished corresponding 2-[2-(4-arylidene-3-methyl-5-oxo-4,5-dihydro-pyrazol-1-yl)alkoxy]-isoindole-1,3diones 6a-l, which on cyclisation with o-phenylendiamine give titled compounds 7a-l. All the synthesized compounds have been characterized by elemental analysis and spectral data and screened for their antibacterial properties against various bacterial strains in order to obtain chemotherapeutic properties.


Introduction
A great deal of synthesis work has been done in last few years on various compounds having a condensed diazepine nucleus, especially benzodiazepin have attracted the attention of several chemist and biologists because of their valuable therapeutic properties like tranquillizer 1-3 , neuroleptic agents 4 , antineoplastic 5,6 , HIV-1 RT inhibitors 7,8 antileukemic 9 and antifungal 10 etc.It is interesting to note that pyrazoles are also reported as well known pharmacophores [11][12][13][14] .As a part of our studies aimed to synthesis of various heterocyclic imidoxy derivatives and in continuation to our work [15][16][17][18] it seems interesting to integrate structural features from different biological active compounds in a single molecule.Consequently there have been many efforts for designing of novel, hybrid molecules possessing significant bioactivity.In the present work, we report the synthetic efforts to 29 G. L. TALESARA et al synthesize alkoxy isoindole-1,3-dionestetra-azabenzo[f]azulenes containing benzodiazepine, pyrazole and imidoxy moieties.
Compounds 6a-l were further cyclized with o-phenylenediamine in dry xylene to give final product 7a-l.Structural assignments of compounds 7a-l are based on IR, 1 H NMR, Mass spectral data and elemental analysis.

Antibacterial Screening
In the present investigation all the synthesized compounds were screened at 100µg/ml against various bacterial strains viz.Escherichia coli, Proteus mirabilis, Klebsiella pneumonia, Pseudomonas aureginosa, Salmonella typhi and Staphylococcus aureus for their antibacterial activity using amicacin as an standard drug by cup and well method developed by Collee, Fraser, Marmion and Simmons 19 .The screening results are summarized in Table 1 indicating that all the synthesized compounds have been manifested moderate to fairly good growth inhibition.Especially, compounds 7b, 7e, 7g, 7i, 7j and 7k have shown strong antibacterial activity as compared to standard.Synthetic and their antibacterial activity studies 32 Table1.Antimicrobial activity of synthesized compounds 7a-l Zone of inhibition (mm)/(activity index)

Conclusion
In the present paper we have succeeded to synthesize alkoxy isoindole-1,3-diones tetraazabenzo[f]azulenes in good yields which have been tested for antibacterial properties.
Although compounds show moderate to good activity but some of the synthesized compounds have shown significant antibacterial activity which reveals the chemotherapeutic values of the synthetic compounds.