D. Rai, Vandana Gupta, R. Gupta
1996
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0
Influential Citations
4
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Quality indicators
Journal
Heterocyclic Communications
Abstract
The synthesis of nitrosourea derivatives of 6-bromo and 6-chloro-2,3-dihydro-l,4benzothiazines by isocyanation and successive nitrosation is reported. Introduction : Phenothiazines are well known heterocycles having a wide spectrum of biological activities. Their several derivatives are in clinical use. Phenothiazines also exhibit significant anticancer activities which have been assigned to their interaction with DNA. Biological activities of phenothiazines have been ascribed to their structural specificity of having a fold along nitrogen-sulfur axis (1). This structural specificity is also present in 1,4-benzothiazines (1,2) having an anticipation to patternize them for anticancer activities. 2,3-Dihydro-l,4-benzothiazines are less toxic and form an interesting class of heterocyclic drugs for anticancer activities. Nitrosoureas are an important class of antitumour agents that have demonstrated activity against a wide range of human malignancies due to their unique chemical and biological characteristics. Several nitrosoureas are clinically significant. They interact with DNA by alkylation (3-7). However, their clinical use is limited, because of cumulative and delayed side effects exerted by these compounds. Therefore, it has been considered worthwhile to develop a series of nitrosoureas with minimum toxicity and side effects. In 4-(N-alkyl/aryl-N-nitrosoamido)-2,3-dihydro-l,4-benzothiazines, heterocyclic nitrogen with a side chain at 4-position constitutes an N-nitrosourea linkage and as such these compounds contain both 1,4-benzothiazine nucleus and a nitrosourea moiety. They will interact with DNA by complexation as well as by alkylation and constitute a new class of Afunctional anticancer agents (8,9). Experimental : Melting points of the synthesized compounds are uncorrected. The purity was checked by thin layer chromatography. Characterization of synthesized compounds was done by spectral studies. The infrared spectra were recorded on Perkin-Elmer spectrometer model 881 using potassium bromide