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ABSTRACT:
The synthesis of piperazine derivatives containing thiophene and oxazole is described. They were prepared from (Z)-3-bromo-N'-phenylthiophene/furan-2-carbohydrazonoyl chloride in a series of steps. All the synthetic compounds are characterized by spectral analyses. They were further analyzed for anti-inflammatory and antimitotic activity and the results are discussed.
KEYWORDS: Synthesis, anti inflammatory activity, antimitotic activity
INTRODUCTION:
Among the synthetic procedures that involve 1,2migration from a carbon atom to a formal six-electron nitrogen atom,1 the Curtius Rearrangement (CR) of carbonyl azides is considered the most convenient and general route,2 especially for the synthesis of fivemembered heteroaryl isocyanates.3
Reactions carried out in anhydrous conditions give isocyanates in very good yields, but in the presence of moisture hydrolytic steps may result in the conversion of carboxylic acids into amines, amides, carbamates or other N-linked heteroarenes.4 The mechanism of the thermal CR process has been the subject of much debate since the pioneering work of Stieglitz.5,6 Other experiments gave results consistent with a concerted route for the thermal reaction.7
The dissociation of five-membered heteroaryl azides exhibits chemical and thermal reactions depend on the 2or 3-azido position on the heteroaryl ring,8 and has been studied as a source of nitrogen heteroaryls.9 Cyclooxygenase enzyme is involved in the process of inflammation. Anti inflammatory activity was evaluated by docking the compound to 5cox. Microtubules are important in cells undergoing mitosis. These contain a and ß-tubulin monomers bound by GTP. Hence in this study, anti mitotic activity was analyzed by docking to 1jff protein which is alpha-beta tubulin.
EXPERIMENTAL SECTION:
Chemical and solvents used were purchased either from Fluka or Merck. All the reagents were of analytical grade. Thin-layer chromatography (TLC) was performed on E. Merck AL silica gel 60 F254 plates and visualized under UV light. IR spectra were recorded as KBr pellet with a perkin-elmer spectrum gx FTIR instrument and only diagnostic and/or intense peaks are reported. JH NMR spectra were recorded in DMSO- d6 with a Varian Mercury plus 400 MHz instrument. Signals due to residual protonated solvent (1 H NMR) served as the internal standard. All the chemical shifts were reported in 5 (ppm) using TMS as an internal standard. The JH NMR chemical shifts and coupling constants were determined assuming first-order behavior. Multiplicity is indicated by one or more...