Synthesis of 3,4-diaryl-4-thiazoline-2-thione derivatives as new potential COX-2 inhibitorsc-MIBI myocardial perfusion imaging

Background and Nonsteroidal anti-inflammatory drugs (NSAIDs) remain among the most widely prescribed drugs worldwide for the treatment of inflammation including pain-releasing, anti-pyretic and rheumatoid arthritis. The conventional NSAIDs exert their effects by inhibiting cyclooxygenase (COX) enzymes. Subsequent research and rational drug design validated the initial concept that a selective COX-2 inhibitor would illicit effective anti-inflammatory without the adverse ulcerogenic effect associated with the use of NSAIDs that inhibit both COX-1 and COX-2. Accordingly, in this work we report the synthesis of a new diaryl heterocyclic series, the 3,4-diaryl-4-thiazoline-2-thione, as potential selective COX-2 inhibitors. The starting material thioanisole underwent Friedel-Craft reaction with acetic acid in the presence of trifluoroacetic anhydride followed by oxidation by MCPBA to give 4-(methylsulfonyl) acetophenone. This compound was then treated with Br2 in CHCl3 to give phenacyl bromide derivative. On the other hand, condensation of aniline derivatives with carbon disulfide in the presence of triethylamine gave the corresponding dithiocarbamate salt. Subsequently, reaction of aryl dithiocarbamate with methylsulfonyl phenacyl bromide furnished cyclic alcohol intermediate, which was dehydrated by 80% H2SO4 to give 3,4-diaryl-4-thiazoline-2-thione. All of the target compounds were characterized by their 1H-NMR, 13C-NMR, IR and mass spectral data. In view of the pharmacological importance of the selective COX-2 inhibitors, a series of 3,4-diaryl-4-thiazoline-2-thiones having pharmacophoric features of COX-2 inhibitors have been synthesized via convenient and efficient synthetic pathway, and structurally characterized by different spectroscopic methods.