| 摘要: | Pyrazole-based heterocyclic compounds were also enthusiastic investigated in pharmacochemistry and agrochemistry. ,2 We develop an efficient and conveniently synthesis method by using 1,3-diploar cycloadditions of sydnones onto triple bonds to prepare pyrazole-based compounds. To begin, we focused on the synthesis of pyrazole DHODase inhibitors. Helicobacter pylori is a Gram-negative microaerophilic bacterium that infects up to 50% of the world’s human population. In 2000, Copeland et al.,3 reported that the pyrazole-based compounds 1 are potent and selective inhibitors of the dihydroorotate dehydrogenase of Helicobacter pylori (H. pylori DHODase). Herein, we successfully controlled the regioselectivity of 1,3-dipolar cycloaddition between 3-aryl-4-cyanosydnones and propargylic esters by using the highly hindered diphenylmethoxy propiolate. Furthermore, following amination and Ritter reactions provided a convenient and efficient access to pyrazole DHODase inhibitors. CDPPB [3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)BENZAMIDE, 2] was recently decribled as the first centrally active, positive allosteric modulator of rat and human metabotropic glutamate receptor (mGluR) mGluR5 subtype. We explored the new convenient synthesis method to provide CDPPB in 3 steps (1,3-dipolar cycloaddition, Pd-coupling reaction, and amination). 1,5-Diarylpyrazoles are afforded as a new potent class for cyclooxygenase-2 (COX-2, 3) inhibitors. Herein, we are also going to develop a key step by using the 1,3-dipolar cycloaddition between 3-(p-sulfonamoylphenyl)-4-phenylsydnone with propargylic compounds to provide 1,5-diarylpyrazoles as a major product for cyclooxygenase-2 (COX-2) inhibitors. |
