Dimerization of sumatriptan as an efficient way to design a potent, centrally and orally active 5-HT(1B) agonist

Michel Perez, Petrus J. Pauwels, Catherine Fourrier, Philippe Chopin, Jean Pierre Valentin, Gareth W. John, M. Marien, Serge Halazy

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

A new bivalent ligand of formula 3 which results from the covalent coupling of two sumatriptan molecules with a p-xylyl spacer at the level of the sulfonamide nitrogen has been prepared and evaluated as a 5-HT(1B/1D) receptors agonist. In vitro experiments at 5-HT(1B) human cloned receptors (Ki = 0.64 nM; EC50 = 0.58 nM) and at the level of the contraction of the New Zealand white rabbit saphenous vein (pD2 = 6.6) demonstrate the superior potency of dimer 3 as a 5-HT(1B) receptor agonist when compared to sumatriptan or zolmitriptan. Interestingly enough, the new bivalent agonist 3 was found to induce hypothermia in the guinea-pig upon oral administration suggesting good oral activity and access to the brain.

Original languageEnglish
Pages (from-to)675-680
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume8
Issue number6
DOIs
StatePublished - 17 Mar 1998
Externally publishedYes

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