Studies On The Synthesis And Bioactivity Of Frovatriptan And Its Analogs

The pathogenesis of migraine and the therapeutical function for 5-HT_1B/1D receptor agonists were reviewed in this paper. The pharmacological peculiarity of frovatriptan, one of the second generation triptans, was introduced in detail and its synthetic process was studied systematically. Frovatriptan was synthesized via 5 steps and the total yield was around 23%. Six analogs of frovatriptan (FP, FPr, FM-1, FM-2, FM-3, FM-4) were also synthesized in this paper and their chemical structures were certified by spectral detection. Five of them, including FP, FM-1, FM-2, FM-3, FM-4, have not been reported in CA.Preliminary pharmacological tests showed that frovatriptan succinate (2:1) and frovatriptan hydrochloride exhibited strong analgesic activity. Among the frovatriptan analogs, 6-carboxamide-3-(1-piperidinyl)-1,2,3,4-tetrahydrocar-bazole(FP) and 6-carboxamide-3-(1-pyrrolidmyl)-1,2,3,4-tetrahydrocarbazole (FPr) exited a steady prolongation of the pain threshold in mice quickly. The 3-morpholinyl derivatives of 1,2,3,4-tetrahydrocarbazole, however, had little effect on the pain threshold.